A century-old tuberculosis vaccine reduced insulin use in people with diabetes, new clinical trial results suggest. The catch: Research on this vaccine has divided the diabetes research community for years.

The Bacillus Calmette-Guérin (BCG) vaccine contains a weakened version of the bacterium Mycobacterium bovis, the germ that causes tuberculosis. Inside the body, the vaccine prompts a protective response against the bacterium. It's also approved to treat bladder cancer, acting as an immunotherapy that rouses an attack against tumors.

The leader of the trials, Dr. Denise Faustman of Massachusetts General Hospital, has long been the subject of controversy. Early on, critics argued that she falsely raised hope that her work could lead to a cure for those with long-standing type 1 diabetes.

On June 5, Faustman and colleagues presented results from two new clinical trials at the annual meeting of the American Diabetes Association in New Orleans. The results suggest the BCG vaccine may offer benefits to people with type 1 diabetes — not by curing the disease, but by improving blood sugar control or slowing the disease's progression, depending on the population. Here's what to know.

Another tool in the arsenal?

About 2 million Americans have type 1 diabetes, an autoimmune disease that destroys insulin-making cells in the pancreas. Patients monitor their blood sugar and inject insulin multiple times a day, carefully calculating every dose. Too much insulin and blood sugar crashes, causing shakiness, seizures or blackouts; too little, and chronically high blood sugar damages the heart, kidneys, eyes and nerves.

Early in the disease process, patients still have some insulin-making cells, but people with longstanding disease have almost none left. Curing type 1 diabetes in those with longstanding disease is a tough problem that requires stopping the immune attack and regenerating enough insulin-making cells to eliminate the need for injected insulin.

The new trial results do not show that level of improvement. However, "the new data suggests that BCG could reduce insulin resistance and decrease the amount of insulin needed in patients with both late-onset and juvenile-onset type 1 diabetes," said Dr. Gillian Goddard, a board-certified endocrinologist at NYU Langone Health who wasn't involved in the studies.

"These are phase 2 trials so further trials will be needed to fully understand the benefits of BCG in Type 1 diabetes," she told Live Science in an email, "but it could be another tool in our arsenal for improving the lives of patients with type 1 diabetes."

Others are more skeptical. Dr. John Buse, an endocrinologist at the University of North Carolina School of Medicine, cautioned that the improvements seen in these small trials may not hold up in a larger trial. The history of type 1 diabetes research "is littered with losers and no blockbuster successes," he told Live Science in an email.

Different trials, different benefits

In the trials, researchers tracked the effect of six doses of the BCG vaccine, administered over five years, on two separate groups of diabetes patients.

In one trial, 34 adults with childhood-onset type 1 received the BCG vaccine and 24 received a placebo. By five or more years later, the BCG group had measurable improvements in blood sugar levels and reduced insulin use, compared to the placebo.

This conclusion was based on hemoglobin A1C (HbA1c) tests, which measure a person's average blood sugar levels over the past two to three months. The vaccinated group went from an average 7.84% at the start of the trial to 7.30% five years later. Historically, a drop of 0.5% has been considered clinically meaningful enough to consider a therapy for approval.

The vaccinated group also spent more time in a healthy blood sugar range, up to 183% more often than they had at the start of the trial. They didn't experience more episodes of dangerously low blood sugar than the unvaccinated group.

The second trial focused on latent autoimmune diabetes (LADA). This is an adult-onset form of diabetes also known as "type 1.5." It's different from type 2 diabetes, which is not autoimmune.

Sixty-eight adults with LADA received the BCG vaccine and 27 received a placebo. The vaccine didn't lower blood sugar readings, but it appeared to slow the disease: Vaccinated patients showed preserved — and in some cases, partially restored — insulin production over five years, as measured by levels of C-peptide, a protein released by the pancreas alongside insulin.

Vaccinated patients also needed less insulin over five years, while those given placebo needed 22% more at the five-year mark than they did at the start of the trial.

"The results exceeded my expectations," Faustman told Live Science in an email.

How does it work?

In the LADA trial, the blood of the vaccinated group carried lower levels of two key antibodies that drive the attack on insulin-producing cells. This hints that the BCG vaccine may protect a person's remaining insulin-making cells from the immune system, the researchers think.

Faustman and her colleagues think that a different mechanism — one they proposed in a 2018 study — is at play in childhood-onset diabetes, where participants had little or no remaining insulin production in their pancreas at the start of the trial.

Uncontrolled diabetes forces cells to use fat for energy, instead of being able to efficiently switch between fat and sugar. From their 2018 study, the researchers concluded that BCG vaccinations specifically help shift immune cells, called regulatory T cells, out of a fat-burning state toward a sugar-burning state. Those immune cells then pull sugar out of the blood but stop once blood sugar declines, thus preventing dangerous crashes, Faustman explained.

Buse said that he can't personally judge whether these proposed mechanisms behind the vaccine's effects make sense. But he does suspect that BCG may work better for some diabetes patients than others; there could be responders and non-responders.

The evidence presented "suggests that there may be a benefit," he said, but the current data is probably not strong enough to say so definitively. "It would take a big program to develop proof and that is probably the biggest barrier to finding out whether it is in fact useful."

The only Food and Drug Administration-approved drug that delays insulin dependence is teplizumab, which is given early in the disease, before patients need insulin. BCG, by contrast, may offer benefits even to patients who have already been on insulin for years, Goddard said.

Faustman's team has now studied over 350 adults, following individual participants for up to eight years, and another trial involving 250 children is currently underway. "This is the next step to prove this safe, affordable and durable drug can work on all stages of T1D," she said.

Regardless of whether BCG improves blood sugar control in type 1, the "path of the future" is using combination approaches that treat the disease on multiple fronts simultaneously, Buse said. Whether BCG would be part of that mix remains to be seen, he said.

"It seems reasonable to proceed further [with research]," he said, "but funders will have to read the tea leaves to decide where to invest their resources among many options."

This article is for informational purposes only and is not meant to offer medical advice.

Epigenetics, which means "above genetics," results in changes to the way an individual's genes act without involving changes to the DNA itself. For example, by adding molecules called methyl groups to DNA — a process called DNA methylation — epigenetics may turn genes on or off, or increase or decrease their activity.

Environmental factors ‪—‬ such as stress, diet and smoking ‪—‬ can fuel epigenetic modifications which can, in turn, lead to conditions such as colorectal cancer and heart disease.

But some of these epigenetic modifications can be reversed. This means that epigenetics can reveal potentially new and targeted ways of modifying disease risk, Alika Maunakea, a professor of anatomy, biochemistry and physiology at the University of Hawaii at Manoa, told Live Science.

Having grown up subsistence-living on a homestead in Hawaii, Maunakea said he learned from a young age that the environment plays a major role in shaping the health of the community.

Now, Maunakea has been researching epigenetics for over 20 years and heads the Maunakea Lab, which focuses on how environmental and epigenetic factors act at the molecular level to fuel health disparities. Live Science spoke with Maunakea to unpack how epigenetics affects health and what his research is uncovering about how epigenetics plays a role in driving health disparities in Native Hawaiians.

Sophie Berdugo: Can you explain how genetics and epigenetics interact in a health context?

Alika Maunakea: It's a little complicated because there's a lot of nuanced differences and variability in understanding the context behind disease risk that's not just shaped by genetic predisposition but also environmental factors and lifestyle, and even things that our grandparents experienced. That's where epigenetics comes in.

Epigenetics is this intermediate state between the environment and the genome, and it helps to regulate the genome. So, even if you carry a genetic risk, it doesn't necessarily mean that risk will play out.

They [genetics and epigenetics] relate to each other because there are certain regions in the genome where if there's a polymorphism — a change — in the sequence, that can sometimes cause a change in the epigenetic patterning. So there's this intertwined connection between the two. In some cases, it's hard to separate completely the genetic variability that's conferring a risk of a particular outcome with epigenetic variability that's contributing to that same risk.

If a lot of the epigenetic variability is contributing to that risk — rather than genetic variability — then there's a chance that there are lifestyle changes, things that you can modify at the individual level to reshape the epigenome, that would then help to reduce that risk. So there's still a lot of work [to be done] around understanding that connection, and it will require a multidisciplinary approach and integrating multiple types of data.

SB: What got you interested in this field?

AM: My great-grandmother was a Hawaiian healer — what we call "kahuna la'au lapa'au" — and she taught me "nā mea Hawai'i," so "all the things Hawaiian." There was a deep understanding and recognition for how maintaining a healthy built and natural environment around us actually does shape our own health and well-being.

I was really interested in understanding why our population, Native Hawaiians, has a higher prevalence of specific chronic conditions which we never had before Westernization, and trying to understand, why do we see it earlier, at a younger age, in our population compared to other populations? That was something that really bothered me. I wanted to understand that more at the cell and gene level, so I think I just gravitated naturally towards epigenetics because I think it explains that phenomenon.

My main goal is really to apply that information into more of a clinical, community-based setting where that information can be used to enable tools and approaches that would help reduce the onset of these disorders in our community.

What we're learning now is that, indeed, epigenetic processes can precede disease symptoms. We can actually identify some of the earlier indicators of disease trajectories before our clinical diagnosis, using epigenetic analyses. Trying to understand how that can play a role in enabling prevention is a real big thing in my lab right now.

SB: Which health conditions do you look at in your research?

AM: One of the conditions that we're looking at is type 2 diabetes, which has such a high prevalence amongst Native Hawaiians. It's three times higher than in other populations in the state, as well as an earlier onset of disorder: about 10 to 15 years younger where Native Hawaiians are diagnosed with type 2 diabetes compared to other populations in the state. [They also have] higher rates of mortality due to type 2 diabetes and other chronic conditions.

Pre-colonization [pre-Western contact in 1778], we never had [chronic conditions like type 2 diabetes] as an issue in our population. Our "kahuna la'au lapa'au" [Hawaiian healer], like my great-grandmother, had to invent new terms for them based on the phenotype [how the condition is presenting]. So we call it [type 2 diabetes] "mimi koko," which is "sweet blood."

It's unclear how much of our genotype is really related to that disease risk, but we think that environmental factors and the changes that happened after colonization and Westernization, and the changes in our lifestyle and our society — disruption and especially displacement — really drove us to this state where there's this higher incidence now of these conditions. And so we're trying to understand what, at the molecular level, is shaping those outcomes and how we can use that information to prevent that from happening in the first place.

One of the questions that really immediately came out was, what's really behind the earlier age of onset? Why do we not only have a higher prevalence, but why is it happening at a younger age? That question still remains to be clarified, but we think that certain traits, like obesity, modify that risk.

To get at that question, then, we really need to understand, at the molecular level, are there disruptions to the aging process in this population? Are there differences in vulnerabilities to aging in this population versus other populations that might be influenced by these environmental factors?

There's a phenomenon called "epigenetic aging," which Steve Horvath back in 2013 initially published a paper around, and identified that there are certain sites in the genome that are epigenetically regulated — by DNA methylation, in particular — that correlate with chronological age really well in a healthy population.

But there were some individuals that exhibited what we would call outliers in this relationship, where there were cases where individuals seem to have higher estimated epigenetic age compared to their chronological age. So they would seem [to be] biologically aging faster than they should be normally. And then there were also people at the opposite end, where their estimated epigenetic age actually appeared younger than their chronological age. And we think that corresponds to health in general.

We found something similar in the Native Hawaiian population: There's a higher frequency of individuals in the Native Hawaiian population that seem to be, at the molecular level, aging faster than they should be compared to other populations, such as white populations and Japanese American populations in the state of Hawaii.

And we know that corresponds to the higher prevalence of these chronic conditions that we see, like diabetes in the Native Hawaiians compared to these other populations, as well as some of these risk factors, like obesity. And we've seen it in our community. Individuals that are in socioeconomically poorer neighborhoods tend to have this accelerated aging.

We're learning that there are certain individual-level lifestyle factors that can actually potentially modify that [epigenetic] risk. We have identified that even amongst Native Hawaiians that are living in socioeconomically poorer areas, at the individual level, if there's a higher degree of physical activity as well as education — and even in some cases, nutrition — there tends to be closer-to-normal biological aging amongst those individuals even within that population.

And so that told us that while there's a higher risk for individuals that have this accelerated aging of diseases like diabetes, that risk could be potentially modified by engaging in healthier lifestyle changes.

Now we're not only seeing that there's this disparity and potentially a mechanism that might underlie that disparity but some clues into potentially what types of environmental factors might be shaping that molecular process.

We have one pilot study that we published a few years ago showing clearly that amongst Native Hawaiians that are diabetic, when they engage in a lifestyle intervention that includes social support, in particular, they not only improve their glycemic control — which is the main purpose of this intervention, really — through this lifestyle modification over a 12-week period, but we also showed that the cells that relate to inflammation, the behavior of those cells, is actually modified by that intervention, and they actually seem to be less inflamed. [Glycemic control is the management of blood glucose levels.]

The epigenomes of those cells are also being modified to a pattern that's similar to a nondiabetic-like state.

So we think those cells play a role in the pathology and the etiology [cause] of the disease and metabolic dysregulation in diabetic individuals. But we also think that modifying their inflammatory state might actually help with improving the glycemic control. So we're trying to understand how much of the epigenetic patterning might be associated with that [inflammation].

We're finding very clear associations that indicate that potentially we can use that information also to identify more effective interventions that might actually target this [epigenetic] process, where we can reduce the inflammatory state of these individuals at the cellular and molecular level.

We're really hoping that it can be useful for prevention, because we can identify these really early, before the clinical diagnosis. [Editor's note: These findings have not been published in a peer-reviewed journal.] And we think that if we can do that at the individual level, especially in a high-risk population, then we can recommend appropriate interventions — or optimize those interventions that exist — to target changes in the epigenome that then have this effect on the physiology and the outcomes of the condition itself. So that's something we're trying to develop further.

SB: How resource-intensive is it to inspect an individual's epigenome?

AM: It is resource-heavy, unfortunately, at this stage. So I think that it will take time to develop new technologies and tools that are more targeted and that can be used in more of a clinical setting.

But with genome sequencing being more cost-effective than it ever was before and the reduced cost that it's now moving towards, that does increase the feasibility to adopt some of these approaches.

Editor's note: This interview has been condensed and edited for clarity.

The patient: A 17-year-old girl in California

The symptoms: The teenager went to an emergency department after experiencing vomiting episodes for about a day. Over the prior three months, she'd also had periodic shortness of breath accompanied by tightness in her chest.

What happened next: A test revealed that the patient's blood sugar was very high. It was 25.2 mmol/L (453 milligrams per deciliter (mg/dL)), whereas a normal blood sugar range for someone without diabetes is between 3.9 and 5.5 mmol/L (70 to 90 mg/dL). A hemoglobin A1C test, which measures average blood sugar levels over the past few months, delivered a result of 12%, with anything higher than 6.4% signaling diabetes.

Doctors learned that the patient had also experienced unusual thirst, excessive urination, unexplained weight loss and fatigue. Based on these symptoms and the high blood sugar, the doctors determined the patient likely had type 1 diabetes and admitted her to the pediatric department for further tests.

They started her on a conservative dose of insulin, but despite that, she often experienced low blood sugar in the mornings. And despite low fluid intake, she still urinated a lot, which is a characteristic symptom of uncontrolled diabetes.

The patient's mother also told doctors that the teen generally tended to "tan easily," though she didn't happen to have a tan at the time of the hospitalization.

"Given her atypical course and persistent findings," the doctors began looking into additional diagnoses that might explain these symptoms, they wrote in a report of the case.

The diagnosis: They considered whether the symptoms pointed to Addison's disease, which affects the adrenal glands located above the kidneys. These glands normally produce hormones that help control the stress response, blood pressure and water-salt balance in the body, but in patients with Addison's, they don't make enough of the hormones. This is most often caused by an autoimmune response, in which the immune system attacks the adrenal glands and undermines their function.

Tests showed that the patient carried antibodies against the adrenal glands, suggesting that such an autoimmune response was unfolding. Additionally, she had high levels of adrenocorticotropic hormone (ACTH), a signal the brain sends out in an attempt to crank up the activity of the adrenal glands; and renin, which the kidneys make when the body's water-salt balance is off.

At the same time, the brain also releases more of a hormone that drives up pigmentation in the skin, which can cause it to "tan."

These findings confirmed diagnoses of both type 1 diabetes and Addison's disease. Together, these diseases point to another, relatively rare condition called autoimmune polyendocrine syndrome type 2 (APS-2). This syndrome affects various hormone-making glands and is estimated to affect about 1.5 to 2 in 100,000 people.

The treatment: The patient received both short-acting and long-acting insulin to manage her diabetes. For Addison's disease, she was given a number of steroids to help boost levels of two key hormones: cortisol and aldosterone. These hormones, which are normally made by the adrenal glands, work together to manage blood pressure, fluid balance and stress responses. "This dose [of steroids] has been managing her symptoms well thus far," her doctors wrote.

Within two months of her diagnosis, she had begun gaining weight, her blood sugar levels had improved, and her ACTH and renin levels had normalized.

"Symptomatically, she has improved," the doctors wrote; "however, given the diagnosis [of] two autoimmune disorders requiring lifelong treatment, she has benefited from the emotional support from a counselor to cope with her new diagnoses and psychosocial stressors at home."

What makes the case unique: APS-2 is a relatively rare diagnosis, characterized by Addison's disease appearing alongside either type 1 diabetes, an autoimmune thyroid disease, or both.

The exact cause of the syndrome is not fully understood, but it has been tied to a number of gene variants, as well as environmental risk factors. Its presentation varies from patient to patient because different organs can be affected in each case. Patients often face delays in diagnosis due to this variation in disease presentation, the case reported authors noted.

"This case is unique because both diseases were diagnosed at the same time of presentation," they noted. "There are few cases that reported the concurrent diagnosis of T1DM [type 1 diabetes mellitus] and Addison's disease at initial presentation."

The case highlights the importance of screening patients with type 1 diabetes for additional autoimmune diseases, the doctors concluded. "Unexplained persistent electrolyte abnormalities" could raise a flag to screen for Addison's, they said, and that screening may include looking for adrenal antibodies, as they did in this case.

"Early detection could help prevent adrenal crisis, reducing morbidity and mortality associated with Addison's disease," they wrote.

For more intriguing medical cases, check out our Diagnostic Dilemma archives.

This article is for informational purposes only and is not meant to offer medical advice.

My first clue that something was wrong was the smell of cotton candy.

It was March 15, 2016, and I was changing my toddler's sheets because he had soaked through his diaper. The bed was wet, but it didn't smell like urine. Other details I'd brushed off came to mind, and I began to worry.

He'd lost his chubby baby cheeks. He'd been finishing his morning sippy cup of water, rather than flipping it over and cackling in glee. And he seemed a bit more tired.

I called the pediatrician, who tested my son's urine. It showed dangerously high sugar levels. After a harrowing trip to the hospital, we had a diagnosis. My son had type 1 diabetes, like 2 million children and adults in the U.S., which meant his rogue immune system had destroyed almost all of the insulin-making beta cells in his body. He was 1 year old.

A decade later, he is a thriving sixth grader.

But in his own words, "diabetes really sucks."

"There are times when I can't eat because my blood sugar is high. Sometimes, when I'm really low, I'm scared that I'm going to die," he told me.

If he lives to old age, he will have changed the sensor that measures his blood sugar and the "site" — the tube that delivers insulin — tens of thousands of times, will have spent more than half a million hours with high or low blood sugar, and will have incurred millions of dollars of medical care. Getting off this blood sugar roller coaster for good would dramatically reshape his future.

"I could get more sleep. And I wouldn't have to do any site or sensor changes, or get shots," my son said. "It would be a better life."

There's a running joke in the type 1 diabetes community that a cure is "only five years away" — and has been for at least 50 years.

But there may be a kernel of truth in it now.

The first treatments to replace destroyed beta cells are in late-stage trials that will likely conclude in the next few years. And scientists are developing innovative ways to keep those transplanted cells alive without harsh side effects.

Many hurdles remain before such treatments can be widely used in kids with the disease. But a picture of a post-type-1-diabetes (T1D) world is emerging. Not too far off, those who have dangerously erratic blood sugars or who already need to suppress their immune systems for other reasons may be freed of the disease with stem cell transplants. And after that, otherwise healthy adults and kids may receive stem cell transplants.

"Cell replacement therapies are our flagship program because we believe it's imminent to provide a functional cure for people with type 1 diabetes," meaning the symptoms of the disease are eliminated, said Dr. Sanjoy Dutta, chief scientific officer at Breakthrough T1D, a nonprofit that supports research and advocacy to prevent, treat and cure the disease.

From death sentence to chronic disease

My son's most noticeable symptom — the sweet smell of his urine — was a textbook sign of the disease. "Diabetes mellitus" (the full name of the disease) means "sweet siphon" in Greek, and its symptoms were first described 3,500 years ago in ancient Egypt.

We now know type 1 diabetes occurs when the immune system mistakenly destroys insulin-producing beta cells in the pancreas, which are clustered in cells called islets.

As a result, the body can't move glucose into tissue. Instead, glucose piles up in the blood, and the kidneys go into overdrive as they try to flush it out. Meanwhile, muscle and fat tissue starves. Without glucose for fuel, the body breaks down fat for energy and turns it into compounds called ketones. This water-intensive process dehydrates the body even further, and these ketones accumulate in the blood, turning it acidic.

A person with untreated type 1 diabetes will be ravenous and thirsty. As they eat and drink, and pee and pee, their body will slowly devour itself as their fat and muscle melt away. Without treatment, a person with type 1 diabetes will invariably go into a coma and die.

The solution to this problem is insulin. In 1921, Frederick Banting and Charles Best isolated insulin from pancreatic islet cells in dogs and eventually devised a way to make insulin from the pancreas of a cow.

Science had transformed type 1 diabetes from a death sentence to a chronic disease — an accomplishment that earned Banting the 1923 Nobel Prize in medicine.

We've come a long way since then. People now routinely live decades after their diagnosis. Scientists have made faster-acting insulin, designed insulin pumps that automate the delivery of the drug, and created continuous glucose monitors that reveal blood sugar levels up to every minute. These innovations improve average blood sugar levels and reduce complications.

But none of these advancements has fundamentally changed the relentless nature of the disease. Injected insulin doesn't work as fast as the version the body produces. And because dozens of factors — including diet, exercise, stress, illness and puberty — can affect how much insulin the body needs, patients are always at risk of under- or overdosing insulin.

"This is a disease that requires 24/7 superhuman management," Dutta told Live Science.

People who inject insulin typically face hours of high and low blood sugar every day. Decades of high blood sugar can destroy the kidneys, damage nerves, and cause blindness and heart attacks. Critically low blood sugar can kill within hours, as the brain is starved of energy.

Despite the medical advances, type 1 diabetes still shortens life expectancy by more than a decade, on average.

Replacing lost cells

The reductions in both the length and quality of life have pushed scientists to continue seeking a cure for diabetes. Merely managing the disease isn't enough.

Since the 1990s, more than 1,000 people worldwide have received transplants of islet cells from cadavers; in the U.S., this remains an experimental procedure, so it is done only in clinical trials. Some of the islet-cell recipients have been cured of the disease — at least for a time.

But the donor pancreases the islet cells are taken from are in very short supply. And cells can be damaged, either before or during harvesting, so their quality is often poor. As a result, cadaveric islet cell transplants aren't very effective; five years after transplantation, only 1 in 10 people who receive them don't need to inject insulin.

Another challenge is that recipients must take immune-suppressing drugs for life. As a result, cadaveric transplants are mostly offered to people who already need another type of transplant, such as a kidney transplant.

For islet transplants to represent a viable cure, they need to be easy to mass-produce in consistently high quality, and scientists must prevent the immune system from destroying the islet cells.

We are getting very close to that first goal: producing high-quality beta cells from scratch.

From embryonic cell to beta cell

In the past several years, scientists have made incredible progress in deciphering the chemical symphony that directs pluripotent embryonic stem cells — cells that can become any type of cell in the body — to morph into islets.

"Even five years ago, I wouldn't have predicted we were as far along as we are," said Lori Sussel, director of basic and translational research at the Barbara Davis Center for Diabetes at the University of Colorado Anschutz Medical Campus, who does basic islet research using mouse and human stem cell models.

Some treatments built on this research are already in late-stage development. For instance, Vertex Pharmaceuticals, a Boston-based biotech company, reported in 2025 in the The New England Journal of Medicine (NEJM) that 10 out of the 12 patients who received the company's embryonic stem-cell-derived product, called VX-880, do not have to take insulin a year out from their transplant. And all of them are making some insulin, Felicia Pagliuca, senior vice president for cell and genetic therapy research at Vertex, told Live Science.

(The two patients who are still insulin-dependent took steroids during treatment against study instructions. Steroids are known to raise blood sugar, which can damage beta cells, the authors of the NEJM study wrote.)

The trial started out with 14 participants, but two people died during it. However, the study authors, and presumably the safety monitoring boards for the trial, concluded that those deaths were unrelated to the treatment. Nonetheless, as with any potential treatment, more data is needed to see if further issues crop up among patients undergoing these transplants.

The company is doing just that, by testing VX-880 in a larger trial that will enroll 50 patients with hypoglycemia unawareness, meaning they can't physically feel when their blood sugar gets dangerously low. These patients face a higher baseline mortality risk, Sussel said. The trial will need a year's worth of data before it can be submitted to the Food and Drug Administration, Pagliuca said. But if those results are positive, that would mean a scalable source of reliable stem cells could be available for some people with type 1 diabetes.

Vertex isn't the only team working on reprogramming cells to become islets. Researchers in China have reprogrammed a woman's own fat cells to become beta cells. One advantage of this approach is that those cells aren't immediately recognized as foreign, because they come from the patient's own body. A downside, however, is that creating a treatment that is unique to each individual is likely to be cost-prohibitive as a broad-scale cure, Sussel said.

Immune invisibility cloak

Creating the stem cells is just the first step. Once they're in the body, they have to survive. That has historically required strong immunosuppressive drugs, just as other transplants do.

Immunosuppressive drugs — such as tacrolimus and sirolimus — leave people susceptible to infections and can damage the kidneys, and may increase the risk of cancer. Tacrolimus is also toxic to the transplanted islet cells themselves, said Dr. Piotr Witkowski, director of the Pancreas and Pancreatic Islets Transplantation Program at UChicago Medicine.

But the average kid with type 1 diabetes has decades of relatively healthy life ahead of them, so putting their heart and kidneys at risk with immunosuppressive drugs presents a higher risk than benefit.

"Immunosuppression is worse than having to take insulin every day," Sussel told Live Science. Thinking about it for my own son, I can't help but agree; diabetes is a huge hassle, but running the risk of fatal infections or higher cancer rates down the line to eliminate that hassle doesn't seem worth it.

Scientists are exploring several ways to solve the immune attack problem.

One is to make transplanted beta cells "invisible" to the immune system. To do that, one company is taking a page from pregnancy. During pregnancy, 50% of the genes — and, therefore, proteins — in the fetus come from the father, said Dr. Sonja Schrepfer, scientific founder of Seattle-based Sana Biotechnology (Hypoimmune Platform) and researcher-scientist at Cedars Sinai Medical Center in Los Angeles.

So Schrepfer's team studied which molecules help shield the fetus from immune attack to sustain the pregnancy.

They identified a few. Two molecules act as unique fingerprints present on the outside of every cell in the body. When the immune system detects a foreign fingerprint, it destroys the cells carrying it. During pregnancy, the fetus dials down how many of these fingerprints are made, especially in the placenta, Schrepfer said. So, to keep transplanted islet cells safe from the immune system, "we have to get rid of that fingerprint," Schrepfer told Live Science.

But that's just the first step in preventing rejection. Certain immune cells, called natural killer cells and macrophages, constantly patrol the body and will automatically kill cells without a fingerprint, she said.

However, Schrepfer's research showed that cells naturally produce a special molecule, at low levels, which essentially screams "Don't kill me." When cells overexpress this molecule, the macrophages and natural killer cells come close to transplanted cells but then drift away, leaving the cells alone, Schrepfer said.

So Sana Biotechnology has used the gene-editing cut-and-paste tool CRISPR, as well as a harmless virus, to genetically modify beta cells collected from a cadaver to lack the cell fingerprints and to overexpress the "don't kill me" molecule. These "hypoimmune" cells are, in theory, tolerated by the immune system.

In August 2025, Sana reported that it had treated the first patient with these cells earlier that year, and in March 2026 said the cells were still evading the immune system and making insulin . While larger safety and efficacy trials are still a ways off, the new results raise hopes that this approach will lead to stem-cell-derived beta cells that don't require immune suppression.

Vertex Pharmaceuticals is also investigating gene-edited stem cell transplants that can evade immune detection, but the company has not tested them in humans yet, Pagliuca said.

Gentler drugs

Other ways to prevent transplant rejection are under development. Unlike the gene-edited islet cells, these methods rely on a more established drug approval pathway.

One is a drug called tegoprubart, which was initially developed to prevent kidney transplant rejection. (It is also in trials as a treatment for delaying ALS progression.)

When immune cells first recognize a foreign protein, they need a second signal to mobilize the rest of the immune system to attack, Witkowski told Live Science. Tegoprubart silences that second "attack signal" by inactivating a molecule called CD40 ligand, he said.

In a study involving 12 patients, Witkowski and his colleagues transplanted cadaveric islet cells and gave the participants tegoprubart instead of the standard-of-care drug, tacrolimus. Tegoprubart led to greater beta cell survival than is typical with tacrolimus.

In March, Witkowski presented results at a diabetes conference showing that all 10 patients who received transplants more than four weeks earlier are so far are insulin-free and as of yet, none of the participants have experienced severe side effects or rejection.

Later this year, the team is also planning to start a 10-person trial with Breakthrough T1D to test tegoprubart in those with kidney dysfunction and T1D — a group that has historically been prevented from undergoing these transplants, Witkowski said.

Moreover, tegoprubart is just one of several gentler immune-suppressing protocols that are currently being studied, Dutta said. Others include antithymocyte globulin and teplizumab, a drug that has been demonstrated to prevent the progression of early-stage type 1 diabetes, he added.

Hope on the horizon

Type 1 diabetes research is littered with dozens of once-promising cures that ultimately fizzled, so it pays to be cautious about these new approaches.

Indeed, there are still some kinks to work out. For instance, when embryonic stem cells are converted to beta cells, most of the resulting cells do produce insulin, but some also make other hormones, such as glucagon, which raises blood sugar, and somatostatin, which inhibits growth hormone, Sussel said. Plus, the process for making these cells is laborious and time-consuming.

"Scaling it up is going to be very expensive, and so I think right now, that's probably one of the rate-limiting steps, is the expense," Sussel said.

And, of course, longer-term studies will need to pin down how long stem cell transplants will last and whether they need to be readministered periodically. There could also be side effects that take years or decades to emerge. As a parent, I'd have to be confident the deaths seen in the Vertex trial were completely unrelated to treatment before I'd be on board.

Everyone I spoke with was wary of pinning a time frame to a post-diabetes future.

"I would hate to say we're five years away," Sussel said. "What I would say is that there is a cure on the horizon."

But there was a palpable excitement among the researchers I spoke with, all of whom said breakthroughs are coming at a rapid pace.

A world where no one has type 1 diabetes is still a long way off. But little by little, a functional cure is coming for more and more people.

"Ideally all people receive it one day, but we're going to start small and then go big," Dutta said.

My son realizes he probably won't see a cure for a while. But knowing something is coming gives him hope. And that would make it all the more heartbreaking if these treatments don't pan out.

"When I imagine myself as an adult, I don't see myself with diabetes," he said.

"I'll be very disappointed if these treatments don't work."

Rates of diabetes are lower in high-altitude locations, but researchers have been unsure why. Now, a new study in mice reveals a possible explanation: Red blood cells, which play a pivotal role in transporting oxygen throughout the body, may lower blood sugar by converting glucose into a compound that helps release oxygen into tissues.

If the results can be replicated in people, they also hint that drugs in early-stage development could potentially mimic this pathway.

"The work highlights the important role that red blood cells can play in diabetes regulation," study lead author Isha Jain, a biochemist at the Gladstone Institutes and the University of California, San Francisco, told Live Science. "That's the concept to be targeted in the future."

Higher altitude, lower blood sugar

It's well-known that people living at high altitudes with low oxygen levels, such as the Andes and the Himalayas, tend to have lower rates of diabetes, but the reason for the link has not been clear. In a 2023 study, scientists observed the same phenomenon in mice: When the mice were exposed to low-oxygen conditions, they developed a condition called "hypoxia," which occurs when oxygen supply to tissues is insufficient, and their blood glucose also dropped.

But the disappearing glucose couldn't be explained by the amount of glucose absorbed by the muscles and other organs in the scans, so it wasn't clear where it was going.

From high altitudes to lab chambers

To test whether red blood cells were responsible for lowering glucose, the study authors exposed mice to low-oxygen chambers containing 8% oxygen. This mimicked high-altitude air, while another group of mice was kept in air with 21% oxygen, which mimicked normal atmospheric conditions, Jain said.

After several weeks, both groups of mice were given glucose injections, and their blood sugar levels were measured over time. Compared with the mice in normal oxygen environments, the mice in low-oxygen conditions showed a much smaller spike in their blood sugar levels, suggesting that they could clear glucose from their blood faster. This effect persisted for weeks, even after the animals were returned to normal oxygen levels, suggesting that a low-oxygen environment had a lasting impact on metabolism, experts said.

The researchers also took imaging scans to track how much glucose was being absorbed by major organs and tissues, such as the liver and muscles. However, a large fraction of the disappearing glucose could not be accounted for. This prompted them to investigate whether cells in the circulating blood itself might be consuming the glucose.

To test this idea further, they manipulated red-blood-cell numbers directly. The team periodically removed blood in oxygen-deprived mice to keep red-blood-cell levels near normal, and found that doing so eliminated the glucose-lowering effect of hypoxia. In contrast, transfusing red blood cells into mice breathing normal air caused blood glucose levels to fall, suggesting that the number of red blood cells alone drove down glucose levels.

Next, the team injected mice with labeled glucose and tracked it through the body. They found that red blood cells from the oxygen-deprived mice absorbed substantially more glucose than those from the comparison mice. The mice in low-oxygen conditions rapidly converted glucose into a molecule that binds to hemoglobin, the protein in red blood cells that carries oxygen. This binding forces hemoglobin to release oxygen more easily into tissues when oxygen levels are low.

Further analysis showed that red blood cells produced in the oxygen-deprived mice also contained higher levels of a protein called GLUT1, which sits on the cell membrane and helps glucose enter the cell. These red blood cells had about twice as much GLUT1 and took up roughly three times more glucose than normal red blood cells. By labeling existing red blood cells before exposing the mice to low-oxygen conditions, the researchers confirmed that only the new cells produced under low-oxygen conditions showed these adaptations.

Besides triggering an uptick in red blood cells, the study shows that the cells are structurally changed to consume more sugar in low-oxygen environments, said Daniel Tennant, a hypoxia and metabolism researcher at the University of Birmingham who was not involved in the work.

Lars Kaestner, a red blood cell biologist at Saarland University in Germany who was not involved with the study, noted that red blood cells are known to increase in number when the air is thin, to boost oxygen transport around the body. Red blood cells use glucose as fuel. Therefore, it's not surprising that low-oxygen conditions lead to lower blood glucose levels, as more red blood cells are there to clear it, he told Live Science.

"From a systemic point of view, this makes a lot of sense,” he said.

It's an "evolutionarily conserved corrective mechanism" to essentially better oxygenate the body at high altitudes, Tennant told Live Science.

The body increases its red-blood-cell count at high altitudes by changing the expression of genes that control metabolism and producing more of a hormone called erythropoietin, which triggers the bone marrow to churn out more red blood cells, said Sonia Rocha, a biochemist at the University of Liverpool who was not involved in the study.

This is why elite athletes train in high-altitude areas for their competitions: Their bodies make more red blood cells and thus achieve "more efficient circulation to distribute oxygen to their tissues," she told Live Science.

A diabetes drug that mimics oxygen deprivation?

In another experiment, the researchers treated mice with HypoxyStat, an experimental compound that was developed in Jain's lab and increases how strongly hemoglobin binds to oxygen, preventing its release and mimicking hypoxia. The idea is that mimicking oxygen deprivation with a drug could boost red-blood-cell counts and help regulate blood sugar levels.

However, much more testing is needed before a drug like HypoxyStat could be tested in humans, Rocha noted.

While transfusing red blood cells is not a practical therapy for diabetes, the findings suggest potential directions such as engineering RBCs that act as better glucose sinks, the authors suggest. “It opens the door to thinking about diabetes treatment in a fundamentally different way,” Jain said in a statement.

An inexpensive drug that's been used for decades in transplant surgeries can delay the progression of type 1 diabetes in those newly diagnosed, new research suggests.

In previous studies, a high dose of the immune-suppressing drug polyclonal antithymocyte globulin (ATG) reduced the loss of insulin-making cells in the pancreas, called beta cells. The new study shows that a much smaller dose is almost as effective at slowing disease progression in type 1 — but with fewer side effects.

In type 1 diabetes (T1D), the immune system destroys the body's beta cells, which produce insulin, the hormone that allows glucose from the blood to enter cells, where it is used as fuel. Without enough insulin, glucose piles up in the bloodstream.

But there's a window of time soon after diagnosis, called the "honeymoon phase," in which beta cells still produce some insulin; this provides an opportunity to keep those remaining beta cells alive longer. A longer honeymoon phase and more residual beta cell function are tied to reduced risk of diabetes complications, such as heart and kidney disease, down the line.

It's this honeymoon phase that the new study was targeting. The study included 117 participants, who were between the ages of 5 and 25 and had been diagnosed with type 1 diabetes within nine weeks of starting the trial. The participants received either a high, intermediate or low dose of ATG: the high dose was equivalent to 2.5 milligrams of ATG per kilogram of body weight; the intermediate dose was 1.5 mg/kg; and the low dose was 0.5 mg/kg of body weight.

The researchers found that the lowest dose preserved beta cell functioning for a year, according to the paper published Sept. 27 in the journal The Lancet.

The trial was designed to help researchers analyze the lowest effective dose in children as young as 5 years old, lead study author Dr. Chantal Mathieu, endocrinologist at the University Hospital Gasthuisberg Leuven in Belgium, told Live Science. That's because the drug's side effects — such as harmful immune reactions — can be especially hard on them, she said.

"The ATG worked wonderfully," she said. The beneficial effect "was the biggest in the smallest children."

This was the third study to confirm the effectiveness of ATG to delay beta cell loss, Mathieu added.

Notably, when researchers reviewed the data, they found a similar level of side effects in the intermediate- and high-dose groups, so they dropped the intermediate dose from further study. The biggest difference between the remaining high- and low-dose groups was the incidence of side effects. One of the most common ATG side effects is serum sickness, an immune reaction to foreign proteins that can be triggered by drugs made in the cells of other animals. (ATG is produced in the cells of rabbits and horses.) In the new study, serum sickness impacted 82% of the participants in the high-dose group and just 32% in the low-dose group.

Meanwhile, in the low-dose group, 24% had cytokine release syndrome, a runaway inflammatory response that can include fever, nausea, fatigue, headache, and muscle and joint pain. About 33% of the participants who received the higher dose developed the syndrome.

"I think the reason this is somewhat promising is that it's now one of a handful of drugs that show you can delay type 1 diabetes somewhat," Mathieu said. Another benefit of ATG, Mathieu said, is that it's inexpensive and widely available.

Other medications that have been found to delay diabetes are teplizumab-mzwv (brand name Tzield) and baricitinib (Olumiant). Tzield is given as a 14-day infusion, but it's only approved for use in "stage 2" diabetes — at which point the body has been making antibodies to insulin and has some abnormal blood sugar responses, but most of its insulin-making cells are still working. Few people are diagnosed with diabetes in this early stage, which limits the drug's reach.

Meanwhile, baricitinib — a rheumatoid arthritis drug that hasn't yet been tested in children with diabetes — must be taken continuously to prevent disease progression.

Good news for young children

Dr. Jennifer Sherr, an endocrinologist and professor of pediatrics at Yale School of Medicine, who was not involved in the study, said the results were encouraging, especially for families who would find it extremely challenging to take off from work for their child to receive two days of infusions. In the study, those in the low-dose group received an infusion on the first day and a placebo on the second day, but the placebo day wouldn't be necessary if the drug were given outside a clinical trial, she noted.

Sherr also liked that the study included 5- to 11-year-olds. "Those are the kids who lose their beta cells so fast" after diagnosis, Sherr told Live Science. "Their insulin needs go up incredibly."

Sherr hopes that this less-expensive medication could ultimately be approved for use in diabetes to help give "kids a smoother ride," she said.

As for whether ATG is better than other alternatives demonstrated to delay progression, "many people think it's going to take a multi-agent approach," she said. In other words, to really stop T1D in its tracks, people would likely need to get multiple drugs, Sherr said.

It's premature to say one treatment is better than another. "I think what gives us hope for the future is [that] there are lots of things we can consider," Sherr said.

And in a clinical trial set to begin late this year or early next year, researchers will test a next-generation version of ATG made in genetically modified cows in people newly diagnosed with type 1 diabetes.

The new drug, made by SAB BIO and called SAB-142, is grown in a cow that has been gene edited to produce human antibodies, said lead researcher Dr. Michael Haller, chief of pediatric endocrinology at the University of Florida's Diabetes Institute and advisory board member for SAB BIO. . "The cow can then donate blood," from which the human antibodies are harvested, Haller told Live Science in an email.

The hope is that, because the antibodies are made using human genes, they will no longer trigger serum sickness in patients. The human antibodies are also less likely to cause the immune system to produce antibodies that block the drug's action, so in theory, Haller said, "the new drug may be safer and even more effective in type 1 diabetes."

Editor's note: Haller holds stock options in SAB BIO, in addition to being an advisory board member.

This article is for informational purposes only and is not meant to offer medical advice.

Scientists have cured type 1 diabetes in mice, without long-term immune suppression.

In type 1 diabetes, the immune system attacks insulin-producing cells, and replacing them with transplanted cells from donors has historically required people to take strong immunosuppressants for life, which severely limited the reach of such transplants.

But in a new study, researchers created a "chimeric," or blended immune system that contains elements of both the recipient's and the donor's immune systems. This enabled mice to tolerate a transplant of insulin-producing cells without long-term immune suppression.

Much more research is needed before this kind of treatment could be available to patients in a clinic, and keeping the blended immune system balanced is tricky. But if extensive follow-up testing in humans shows the transplantation process is safe and durable, it could offer an avenue for reversing the potentially deadly disease.

"This is potentially a way to cure diabetes," Dr. John DiPersio, an oncologist at Washington University in St. Louis who researches cellular therapy but was not involved in the study, told Live Science. "It does represent, in theory, a big step forward."

Inducing intolerance

In type 1 diabetes, the immune system mistakenly attacks insulin-producing cells, or islets, in the pancreas. Without insulin, blood sugar rises and people eventually die, so people with the disease must take insulin for life. Even with the best treatment available, people with type 1 diabetes still face high rates of complications such as heart disease, kidney disease and eye damage.

For decades, scientists have been trying to cure the disease by replacing destroyed islets with new ones, such as those harvested from cadavers. But to keep the body from attacking the transplanted cells, patients must take strong immune-suppressing drugs for life. As a result, islet transplants are typically performed only in clinical trials and in patients who need another organ replacement, such as a kidney or liver transplant.

Using bone-marrow stem cells and islet cells from the same donor could solve the immune rejection problem. The stem cells, which are transplanted into special niches in the bone, would regenerate the white blood cells of the immune system. The new, regenerated immune system wouldn't have the islet-attacking cells and would recognize the transplanted islets as "self," rather than foreign.

But that process required eliminating the host's own bone-marrow stem cells. "It's like musical chairs," study lead author Dr. Judith Shizuru, a professor of medicine at Stanford University, told Live Science. "If you don't get the recipient stem cells out of the niche, you can't get the donor cells in."

In the past, the process required chemotherapy and radiation to completely wipe out the host's immune system, which leaves people vulnerable to infection for weeks.

Shizuru's team wondered if there was a less-toxic regimen that could reeducate the host's immune system, rather than erasing it. "If you have a mixture of donor and recipient, the donor's immune system ‪—‬ the blood system ‪—‬ can influence the behavior of the [immune cells] of the recipient," Shizuru said.

They came up with a multistep process that uses multiple antibodies, low-dose radiation and a rheumatoid arthritis drug called baricitinib, and tested that protocol in more than a dozen mice. This immune system "conditioning" process made space in the recipient's bone marrow for some donor stem cells, without wiping out all of the recipient's stem cells. It also muted different parts of the immune system just long enough for the donor's stem cells and islets to take root.

This allowed the team to transplant bone-marrow stem cells and islets ‪from the same donor into the recipient mouse. As the donor stem cells matured, the cells educated the rest of the recipient's immune system to tolerate the foreign tissue. The mature, blended immune system also culled recipient cells that had been trained to specifically attack islets, thereby eliminating the cells that fuel autoimmunity. "The graft sticks and stays," Shizuru said. "It's there long term."

From start to finish, the process took around 12 days, the immune system was never completely wiped out, and the radiation dose was lower than is typically used in bone-marrow transplants. "We've made this [a] much more gentle regimen," Shizuru said.

The mice were still making insulin 20 weeks later, and blood tests and postmortem analysis showed their immune systems were functioning well and not rejecting the transplants, the study authors noted in the paper, which was published in the January issue of The Journal of Clinical Investigation.

Still, many hurdles remain before this could become a viable treatment in humans, said DiPersio, who was the author of an accompanying commentary piece in the same journal. First, some of the antibodies that worked in mice don't have approved analogues in humans, so this would need to be remedied. Second, the method requires getting both bone marrow and islets from the same donor, and the latter are already scarce.

But a thornier problem is that creating a mixed host-recipient immune system is a delicate balancing act, DiPersio said.

The researchers maintained this balance in mice, but they usually live just a year or two.

For this process to represent a cure, humans would need the different immune system elements to stay balanced for decades. "It's hard to do that over a long period of time," DiPersio said. If the balance shifted, the islets could gradually die or you could get a dangerous tissue rejection reaction, he said.

This article is for informational purposes and not designed to be used for medical advice.

For many people with diabetes, managing their blood sugar levels requires daily insulin shots — but now, scientists have invented a new polymer-based gel that can deliver insulin through the skin without needles.

The gel, described in a November study in the journal Nature, normalized the blood sugar levels of diabetic mice and pigs within one to two hours of application. The animals' blood sugar then stayed in a normal range for approximately 12 hours.

The gel's speed and long-term effects are comparable to that of "basal" insulin shots, which deliver a steady dose that stabilizes blood sugar between meals and overnight. These are typically used together with fast-acting insulin that's used just before, during or after meals to control big spikes in blood sugar triggered by food.

The gel is "mechanistically elegant," said Suchetan Pal, an associate professor and head of the Biomaterials Laboratory at the Indian Institute of Technology Bhilai, who was not involved in the research.

However, for now, it is still strictly experimental. To date, the gel has been tested only on mice and pigs and not on people, Pal told Live Science in an email. Human skin — which is variable in its thickness, fat content and pH — may behave differently than animal skin.

How the gel slips past the skin's defenses

Human skin's outer layer, the stratum corneum, is only about 10 to 15 micrometers thick, thinner than a human hair. But the dead cells and fats that make up the layer form a shield that's tough to penetrate. While some small molecules can cross this barrier, larger proteins, like insulin, normally cannot.

The team behind the study overcame this challenge by engineering a pH-responsive polymer, which they call OP.

At a pH of around 5, the skin's surface is acidic, while deeper layers of the skin are closer to a neutral pH of 7. At the skin's surface, the OP polymer becomes positively charged. This positive charge helps it stick to the fatty acids within the skin, much like opposite ends of a magnet attract each other.

As the pH gradually increases in deeper layers, the OP polymer changes to a neutral state that enables it to diffuse through fats in the skin. Insulin, which is chemically linked to the polymer, is thereby carried through skin layers that it wouldn't normally be able to penetrate on its own.

Lab tests with mouse and pig skin confirmed that OP penetrates all layers of the skin, whereas insulin alone remains stuck on the surface. The researchers then tested whether applying the OP-insulin gel to animals' skin could lower their blood sugar.

In a mouse model of diabetes, applying the gel once lowered their blood glucose to a normal range in about an hour and maintained it within that range for roughly 12 hours. However, Pal noted that this effect required a very high OP-insulin dose of 116 units per kilogram of body weight (U/kg) — far beyond a typical human dose of insulin. ​​This could raise a concern that the insulin delivery through the skin might not be efficient enough.

But notably, the researchers were able to use a lower dose in diabetic miniature pigs, whose skin closely resembles that of humans. Using a single dose around 7.25 U/kg, the gel restored the pigs' blood glucose to normal levels. And using the gel repeatedly caused no skin irritation or inflammation, the team found.

More research needed

If these animal results translate to people, the needle-free insulin gel could potentially help patients with a fear of or aversion to needles, thus helping improve their treatment adherence and easing the burden of diabetes management.

The 12-hour effect suggests the gel could serve as a long-acting insulin to provide "background" blood-sugar control, although patients would still need fast-acting doses at mealtimes. Because the gel's absorption into the bloodstream is slower and steadier than that of an injection, it cannot quickly reverse high blood sugar in an emergency, Pal noted.

The authors hope this polymer approach could extend beyond insulin delivery, as they're working to adapt OP to carry GLP-1 agonists, such as semaglutide (Ozempic), and other therapeutic proteins. However, experts cautioned that hurdles remain before the gel could be approved for human use.

"The polymer hasn't shown any side effects in mice or pigs," said lead study author Youqing Shen, a professor in the School of Chemical and Biological Engineering at Zhejiang University in China, told Live Science in an email. "But humans have used insulin for decades, so we need to investigate long-term toxicity."

Shen also said the insulin dose delivered through the gel must be carefully controlled, since too much can result in dangerously low blood sugar. In sum, developers would need extensive preclinical safety studies, an Investigational New Drug (IND) filing with the Food and Drug Administration, and human clinical trials before a skin-based insulin therapy could reach patients.

While the pig experiments offered a better model of human skin than the mice did, Pal also cautioned that the lower dose of insulin had lower efficacy. This underscores the amount of development still needed to achieve effective insulin delivery at safe and clinically relevant human doses.​​ The long-term safety of using the gel repeatedly is also unknown.

Looking forward, the team will need to figure out the optimal formulation and dosing for the gel; devise a way to scale up its manufacturing; and run clinical trials, Pal said. Nonetheless, he finds the idea exciting and believes it could create an avenue for needle-free diabetes care.

This article is for informational purposes only and is not meant to offer medical advice.

Supplying nerves with a fresh supply of mitochondria could curb chronic nerve pain, a new study hints.

The research, conducted with mouse cells, live mice, and human tissues, reveals a previously unsung role of mitochondria, the powerhouses of cells. It shows that support cells within the nervous system can ship mitochondria to the nerves that respond to pressure, temperature and pain. But problems with that shipping process can deplete the nerves' energy reserves, causing them to malfunction.

Whereas nerves would normally send a signal to the brain in response to some stimulus, dysfunctional nerves "fire sometimes spontaneously, even without stimulation," said senior study author Ru-Rong Ji, director of the Duke University School of Medicine's Center for Translational Pain Medicine and a professor of anesthesiology and neurobiology.

"That will drive chronic pain and also will lead to neurodegeneration," Ji told Live Science, "because if you fire like crazy, eventually, that neuron probably will degenerate."

The new study, published Wednesday (Jan. 7) in the journal Nature, points to potential new ways of heading off that neuronal breakdown — and one strategy could involve transferring mitochondria directly into nerves.

Fresh mitochondria reduce pain

The research zoomed in on satellite glial cells, unique cells that physically wrap themselves around the "roots" of nerve cells located near the spinal cord. The bodies of these nerve cells cluster together near the spine, and from each cluster, bundles of long fibers extend to different parts of the body, from head to toe. The longest of these fiber bundles belong to the sciatic nerve, which measures just over 3 feet (1 meter) long.

The sheer length of the fibers poses a "real challenge," because for a nerve to function properly, mitochondria made in the nerve's root must travel down to the end of each fiber, and that in itself requires energy to do, Ji said. That raises a question of how nerves maintain this power-hungry supply chain.

Scientists once thought that cells had to make all of their own mitochondria, but in recent years, they have uncovered evidence that cells swap mitochondria. This can occur between cells of the same type or between cells of different types, such as between a stem cell and an immune cell, for example. To facilitate the swap, cells construct tiny structures called tunneling nanotubes for the mitochondria to travel through, like spitballs sliding from one end of a straw to another.

Ji and his team wondered whether satellite glial cells might be able to send mitochondria to the nerve cells they encircle — and it turns out that they can.

"We demonstrate that these cells actually extend these tunneling nanotubes to deliver in the mitochondria. This [finding] is unique in this study," Ji said.

In a series of experiments with mouse cells and human tissues, the researchers took snapshots of the tiny tubes that formed between glia and nerve cells, noting distinct "bulges" that appeared in the tubes as materials traveled through them. By tacking a fluorescent tag onto mitochondria, they were able to track instances in which powerhouses from glial cells made their way into the nerves.

The nanotubes were transient structures that broke down soon after a given transfer was complete. Experiments showed that a protein called MYO10 was critical to the tubes' construction, helping to extend them out from the glia. But additionally, the mitochondria could sometimes be transferred without the tubes, either inside tiny bubbles released by glia or through special channels that formed between the membranes of the donor and recipient cells.

In healthy lab mice, the researchers found that disrupting these different modes of mitochondria shipment made the mice more sensitive to pain. That's because it spurred damage in the nerves and caused them to fire abnormally.

They also looked at mice with various types of nerve damage, such as from exposure to chemotherapy drugs or from diabetes. These nerve-damaging conditions also disrupted the mitochondrial exchange from glia to some degree, and this contributed to nerve pain in the lab mice. Transferring healthy glia into the mice alleviated the pain, though, by providing them with a fresh source of healthy mitochondria.

A new view on glia

Notably, nerve damage from diabetes and chemotherapy tends to hit the smallest nerve fibers the hardest, whereas medium and large fibers show more resilience. In the team's experiments, they found that the larger nerve fibers appeared to receive a higher volume of mitochondria from glia, while small fibers got fewer by comparison. In short, it seems that glia have a "preference" toward lending their mitochondria to larger fibers, the study authors wrote.

"That is still a puzzle. We don't know why that's the case," Ji said. But nonetheless, it might begin to explain why small fibers are more vulnerable to damage in these conditions, triggering symptoms of numbness, painful tingling or burning in the feet and hands.

More studies are needed to fully understand how mitochondria are shuttled from glia to nerve cells in health and disease. This fundamental research could pave the way to future treatments for nerve pain, the team thinks. In theory, treatments could be aimed at boosting the activity of satellite glial cells, so they produce and transfer more mitochondria.

Or alternatively, mitochondria could be harvested from cells grown in the lab, purified, and then injected straight into nerves as a treatment, he added.

Historically, glia were solely thought of as the glue of the nervous system, providing structural support to neurons by binding them together. But scientists have since uncovered that glia are involved in processes once thought to be handled only by neurons, like memory. And the new study suggests glia may actually be physically plugged into neuronal networks, Ji said.

"If they can transport mitochondria, such a very large organelle, in that tube, then you can transport many other things, right?" he suggested. "That means the neurons and the glial cells, they are much more connected than we thought."

"Zombified" cells in blood vessels may play a key role in the development of metabolic diseases, like diabetes, with age, a new study finds. And slaying these zombie cells could be a promising approach for future treatments.

Cells usually become senescent — a state in which they permanently stop dividing but linger in the body — as a stress response. These senescent cells may have some useful functions; for example, some play a key role in wound healing. But senescent cells are also known to contribute to age-related diseases, as more and more build up in the body over time.

In previous research with mice, scientists found that targeting senescent cells with drugs can alleviate various signs of aging and extend the animals' healthy life span, lead study author Dr. Mayasoshi Suda, an assistant professor at Cedars-Sinai Medical Center in Los Angeles, told Live Science.

In the new study, published Thursday (Nov. 20) in the journal Cell Metabolism, the team focused on endothelial cells, meaning the cells that line blood vessels, and identified a specific case in which senescence can be harmful to the metabolism. The study also hints at a strategy for treating not only age-related metabolic issues but many aspects of aging, an expert told Live Science.

"By finding a unifying target, such as blood vessels, you open up the possibility that you might be able to, at the same time, target very different aspects of aging," said Dr. Christina Aguayo-Mazzucato, an assistant professor of medicine at Harvard Medical School who was not involved in the study.

Identifying harmful senescent cells

Senescent cells are increasingly recognized as contributors to the development of age-related metabolic diseases. But researchers are still trying to identify specific cells in which senescence is harmful, as opposed to beneficial.

In this study, researchers chose to focus on blood vessel cells, which are critical for the function of most organs and have been shown to help control metabolism in many tissues, study co-author Dr. Nicolas Musi, a professor of medicine at Cedars-Sinai Medical Center, told Live Science.

To identify whether these cells were key drivers of metabolic disorders, the researchers fed one set of lab mice a high-fat diet to raise their body weights and induce senescence in their cells; they then removed their senescent endothelial cells for further study. In addition, the team exposed a different set of endothelial cells to radiation to induce senescence and then transplanted those cells into lean lab mice with normal metabolisms.

Removing senescent endothelial cells from the obese mice was associated with reduced fat mass, improved blood sugar levels and an overall reduction of metabolic dysfunction. Conversely, transplanting senescent cells into lean mice was associated with higher blood sugar levels and insulin resistance.

"When these cells go into this dormant state of senescence, they start producing inflammatory substances that are called Senescence-Associated Secretory Phenotype (SASP)," Musi said. This mechanism helps explain why removing senescent cells was associated with an improved metabolic rate. Cells usually take nutrients from the bloodstream, such as fat and glucose, to create the energy they need to function properly. But when they encounter the onslaught of inflammatory molecules from SASP cells, that process gets derailed, he explained.

"Cellular metabolism gets altered, and that translates into abnormal tissue and then abnormal whole-body metabolism," Musi told Live Science.

'Senolytics' are potential treatments

In a second phase of the study, the researchers treated both groups of mice with fisetin, a drug that the team previously found could eliminate senescent cells. This type of drug is known as a senolytic. In both groups, treatment with fisetin was associated with fewer senescent blood-vessel cells and improved glucose tolerance.

The researchers also tested the drug on tissue samples from six adults with obesity who were in their 40s and 50s. They observed a similar decline in senescent blood vessel cells in the treated tissue.

Aguayo-Mazzucato thinks this study could pave the way for new treatments targeting senescent cells in the cardiovascular system. "Metabolic dysfunction is a whole-body problem. You have nutrient utilization alterations in a lot of tissues," she said. Because senescent vascular cells are present throughout the entire body, targeting them in different organs could help doctors address a range of diseases, she added.

"Rather than say we're going to treat cancer or we're going to treat diabetes, Alzheimer's [or] Parkinson's as defined entities, the idea is saying they're all age-related and there are pathways that are common to all age-related diseases," Aguayo-Mazzucato said.

Future research should include clinical studies that investigate whether senescence has the same effects in human blood vessels that were observed in lab mice, Suda said.

This article is for informational purposes only and is not meant to offer medical advice.

An experimental drug compound could prevent and treat some complications of diabetes, such as poor wound healing and rampant inflammation. And it works regardless of blood sugar control, a new study in mice and human cells suggests.

The cornerstone of diabetes care is keeping blood sugar in check through diet and exercise, by maintaining a healthy weight, and by injecting the hormone insulin to help shuttle glucose out of the bloodstream. But while maintaining blood sugar levels in a target range reduces the chance that diabetes complications will emerge, it doesn't eliminate the risk.

"The complications of diabetes — which really are the issues that make people sick, that reduce their lifespan, and that just make them unwell — are only partly mitigated by tight control of the blood sugar," said study co-author Dr. Ann Marie Schmidt, a professor of medicine at the NYU Grossman School of Medicine and director of the Diabetes Research Program at NYU Langone Health.

That raises questions about what the other drivers of diabetic complications might be and whether they can be treated.

For decades, Schmidt and colleagues have sought to answer those questions, and their efforts have led to the development of the new experimental drug. In their latest work, published in October in the journal Cell Chemical Biology, the team tested the drug's effects in lab mice and human cells.

The results show that such a drug has "great potential" for limiting or preventing several complications of diabetes, Timothy Perkins, an assistant professor of pathology at the University of Pittsburgh, wrote in a commentary on the study.

Blocking complications at the source

The new drug compound takes aim at a protein called RAGE, which interacts with a second protein called DIAPH1. Schmidt and colleagues first described RAGE in the 1990s, finding that it plays a role in the vascular complications of diabetes, such as heart disease.

The RAGE protein is found in many types of cells, including immune cells and the cells that line blood vessels. It spans the cell membrane, with one end interacting with substances on the outside of the cell and the other relaying signals inside the cell. The external bit of the protein interacts with advanced glycation end products (AGEs) — proteins with sugars stuck to them.

"Once they're stuck on there, they have a gain of function where they can actually perturb and damage endothelial cells, the cells that line every blood vessel in our body," Schmidt told Live Science. It's known that AGEs accumulate in the body with normal aging, and in the context of certain chronic diseases, including diabetes, they build up more quickly than usual.

RAGE, which stands for "receptor for AGEs," is activated by this buildup of sugar-coated proteins, and this kicks off harmful changes inside the cell, including processes that ramp up inflammation. It turns out that those changes rely on RAGE's interaction with a second protein inside the cell: DIAPH1. (The team had previously tried blocking AGEs from plugging into RAGE, but didn't find success with that approach.)

With guidance from co-author Alexander Shekhtman, a structural biologist at the State University of New York at Albany, the researchers took a closer look at the interaction of RAGE and DIAPH1. They built a detailed model of how the two proteins interact in the presence of AGEs, and also investigated the downstream cellular consequences of that exchange.

They showed that, at baseline, DIAPH1 starts with a cellular brake engaged that holds back its activity, but after it interacts with RAGE, those brakes are ripped off. The full consequences of that aren't yet understood, Schmidt noted, but from what we know, it "appears to have pathological outcomes."

Schmidt, Shekhtman and their team had previously looked for molecules that could block the interaction of RAGE and DIAPH1. Among 58,000 molecules, the team zeroed in on one that looked promising and found in initial mouse experiments that it curbed diabetes complications such as kidney disease and heart ischemia. An analogue of that original molecule was used for the new study, as tests suggested it has a better safety profile.

In cells from patients with type 1 diabetes, the drug compound blocked the interaction between RAGE and DIAPH1 and subsequently reduced inflammatory signals. In lab mice with diabetes, applying the compound topically to mice's wounds helped to both tamp down inflammation and speed up healing. The researchers also showed that the drug could reduce inflammation in mice with allergies when given by mouth, but they didn't test this oral delivery in diabetic mice.

Looking forward, it will be important to study RAGE in many cell types, because it likely does different things in different types of cells, Perkins noted in his commentary.

Much more work is needed before the drug can be tested in humans, including more tests in lab animals, Schmidt emphasized. But she suggested that, if the drug makes it to approval, it would be best for patients to start using it soon after being diagnosed with diabetes. Ideally, RAGE therapy should be paired with tight blood sugar control, before the snowball effect of AGEs building up could get started, she said. You'd want to "mitigate that spiral of constantly making more AGEs," she said.

Beyond diabetes, RAGE is also known to contribute to inflammatory diseases of the lungs, such as asthma and chronic obstructive pulmonary disease (COPD), Perkins noted. He suggested that those might be additional contexts where drugs that disrupt the RAGE-DIAPH1 interaction might be helpful.

This article is for informational purposes only and is not meant to offer medical advice.

Happiness is known to correlate with better health. But now, researchers have identified a happiness threshold above which people are less likely to die prematurely of chronic diseases like cancer, diabetes and heart disease.

By comparing data from 123 countries over 15 years, researchers pinpointed a threshold at which mortality declined as well-being increased. Every incremental improvement in well-being above this level was tied to a corresponding drop in the risk of death.

Cancer, heart disease, asthma and other chronic diseases accounted for 75% of non-pandemic related deaths in 2021, according to the World Health Organization (WHO). In the U.S., they're collectively the leading causes of illness, disability and death.

Overall chronic disease mortality decreased in the U.S. between 2010 and 2019, but its prevalence increased among Americans ages 20 to 45 years old, according to a study published in The Lancet earlier this year.

A tipping point

Although previous research assumed a positive association between happiness and health, the goal for this new study, which was published Monday (Oct. 20) in the journal Frontiers of Medicine, was to identify a tipping point at which a higher level of well-being would be associated with measurable health improvements — namely, a reduction in premature deaths due to chronic disease.

To do that, the researchers looked at yearly happiness scores in 123 countries, which they averaged to estimate the national level of subjective well-being.

Related: Can faking a smile make you feel happier?

Respondents from the happiness datasets used in the study were asked to visualize a ladder, with the top representing the best possible life and the bottom the worst. They were then asked to rate their present satisfaction and assess their future on a scale of 0 (bottom of the ladder) to 10 (top of the ladder). This tool, known as the Cantril's life ladder scale, is a well-known social science tool used to gauge life satisfaction.

Researchers then compared this measure of national well-being with chronic disease mortality rates in each country over a period of 15 years (2006 to 2021).

The study identified a happiness threshold of 2.7 on the life ladder scale. Above that threshold, every 1% increase in happiness was associated with a 0.43% decrease in premature deaths from chronic disease.

The average life ladder score among the 123 countries studied was 5.45 between 2006 and 2021, so a 2.7 score suggests participants were "barely coping," study co-author Iulia Iuga, a professor at 1 Decembrie 1918 University in Romania said in a statement.

Health effects of subjective well-being

Although the new study doesn't establish a strict cause-and-effect relationship, scientists have identified several ways well-being could have health benefits.

For one, happiness could reduce the impact of stress, which is strongly associated with the development of many chronic diseases.

"We find that positive emotion can serve as a buffer for stressful experiences," said John Hunter, an assistant professor of psychology at Chapman University in California who was not involved in the research."When you have more positive emotion, you have less stress reactivity, which means that when a stressor hits you, you react less severely," Hunter said. "Your heart rate spikes a little bit less; your blood pressure spikes a little bit less. The way that you release stress hormones also changes."

In addition, people with higher levels of positive emotion often maintain stronger relationships and healthier habits.

"People who are optimistic, people who are happy, people who have a more dynamic, happy social life, people who have a strong sense of life purpose [...] tend to be more proactive about their health," said Dr. Alan Rozanski, a cardiologist and professor of medicine at the Icahn School of Medicine at Mount Sinai who was not involved in the study. "They tend to exercise more. They tend to have better diets. They tend to sleep better."

A useful tool for policymakers

The new study could help policymakers think of happiness as a "public health resource" and use it alongside other key factors to mitigate the impact of chronic diseases on their population, the study authors said in a statement.

Policymakers should aim to push their population’s average well-being above the Cantril threshold while addressing trends and environmental conditions that can worsen chronic conditions, such as obesity, alcohol consumption and pollution, Iuga told Live Science in an email.

In places where well-being is lower, focusing on financing healthcare and improving governance is necessary to unlock the positive health effects of increased happiness, Iuga added.

Because the well-being data used in this study is self-reported, it could be subject to measurement errors, the study noted. In addition, various cultures might assess their level of subjective happiness differently.

The life ladder scale used in this study could also be interpreted as a measure of status rather than emotional happiness, Hunter said. So the question may be capturing people’s economic state and living conditions, rather than their emotional state, he said.

Scientists have formally recognized a new type of diabetes, dubbed type 5 diabetes, that is thought to affect 20 to 25 million people worldwide.

The condition, which is most common in Asia and Africa, was first identified more than 70 years ago but remained largely overlooked until now.

Conventionally, medical textbooks describe three main types of diabetes: In type 1, the immune system mistakenly attacks insulin-producing cells in the pancreas, leading to dangerously high blood sugar and a risk of ketoacidosis — a potentially life-threatening condition in which the body breaks down fat for energy. Type 2, the most common form, develops when the body doesn't respond properly to insulin or doesn't make enough of it. Gestational diabetes occurs temporarily during pregnancy, marked by insulin resistance that's thought to be driven by hormonal changes.

Additionally, there are other rare forms of diabetes that can result from specific genetic mutations or diseases. But now, scientists say there's another type of diabetes with a very different cause from the other kinds.

It was formally classified as "type 5 diabetes" during an international meeting of experts in India earlier this year. (They chose the label "type 5" because other researchers have already proposed "type 3" and "type 4" for other forms of diabetes.)

"Type 5 diabetes is characterized by insufficient insulin secretion leading to elevated blood glucose levels, similar to other forms of diabetes," Dr. Rachel Reinert, an endocrinologist and assistant professor at the University of Michigan, told Live Science in an email. "However, type 5 diabetes is not associated with autoimmunity (as in type 1 diabetes) nor insulin resistance (as is common in type 2 diabetes)." It also lacks the features of the more rare type 3 and type 4 diabetes, she said.

"Individuals with type 5 diabetes typically have low body weight and a history of undernutrition starting in early life," Reinert said. Doctors think that chronic undernutrition damages the pancreas early in life, leaving its insulin-producing cells permanently weakened. So the pancreas cannot make enough insulin, but if a patient is given insulin as treatment, their cells are able to respond to it.

Treatment for type 5 diabetes needs to be managed carefully as too much insulin, coupled with too little food — a common reality in low-income countries — could result in dangerously low blood sugar. "It is important for all patients with diabetes to know which specific type of diabetes they have, so they can get the right treatment," Reinert said.

The YODA study

Earlier this year, the Young-Onset Diabetes in sub-Saharan Africa (YODA) study, published in The Lancet Diabetes & Endocrinology, renewed interest in the condition. The team initially set out to investigate type 1 diabetes among nearly 900 young adults across Cameroon, Uganda and South Africa.

But when the researchers analyzed blood samples, they found that roughly two-thirds of participants lacked the autoimmune markers seen in type 1 diabetes. Further testing revealed that these individuals still produced small but measurable amounts of insulin, unlike classic type 1 cases. But their insulin levels were below the range typically seen in type 2 diabetes. These findings pointed to a distinct, non-autoimmune, insulin-deficient type of diabetes.

This was not the first time in history that the condition had been observed.

In the early 1950s, British physician Philip Hugh-Jones encountered a group of 13 patients at his diabetes clinic near Kingston, Jamaica, whose symptoms did not fit type 1 or type 2 diabetes. Hugh-Jones called their condition "type J," for Jamaica, but the label was forgotten and the condition was overlooked for decades.

What's in a name?

Correctly naming a disease not only helps guide clinicians to the best treatment options, it can also help researchers to track its prevalence and identify which factors affect patients' outcomes, Reinert said.

Although type 5 diabetes has likely existed for decades, a lack of research has kept it poorly understood. Recognition is key to ensuring the condition is no longer overlooked, said Chittaranjan Yajnik, director of the Diabetes Unit at KEM Hospital in Pune, India, and co-author of an international consensus statement on type 5 diabetes published in The Lancet Global Health.

"It needs further research and funding to study its aetiology [causes], mechanism and treatment," he told Live Science in an email. "Name is important to attract attention from stakeholders and funding opportunities. Otherwise it will get buried in the background noise of common varieties of diabetes."

This article is for informational purposes only and is not meant to offer medical advice.

A man with type 1 diabetes has become the first patient to produce his own insulin after receiving genetically engineered cell transplants, without needing drugs to prevent rejection.

The case, published this month in the New England Journal of Medicine, marks a potential breakthrough in the treatment of the disease, which affects 9.5 million people worldwide.

Type 1 diabetes occurs when a patient's immune system destroys specialized cells, called islet cells, in their pancreas that are responsible for producing insulin, the hormone that regulates our blood sugar levels. The condition can be managed with regular doses of synthetic insulin, but there is no cure.

Islet cell transplants can provide a longer-term supply of insulin for people with type 1 diabetes. However, after receiving a transplant, the patient’s immune system can recognize the new organ as a foreign object, triggering a response that can destroy the transplanted tissue. As a result, transplant patients must take immunosuppressive drugs for the rest of their lives, which leaves them susceptible to infections.

To overcome these hurdles, scientists in Sweden and the United States transplanted islet cells from a donor's pancreas that had been genetically modified using CRISPR technology to suppress rejection by the recipient's immune system. This is the first time the treatment has been tested on a human.

Related: CRISPR 'will provide cures for genetic diseases that were incurable before,' says renowned biochemist Virginijus Šikšnys

Twelve weeks after receiving the genetically-modified cells, the transplant recipient has continued to produce insulin without an immune response.

In their paper, the authors wrote that their study, although preliminary, suggested that genetically engineering transplant cells to evade the recipient's immune system was a valuable tool for avoiding rejection of new cells or organs by the immune system.

In this new approach, the researchers used CRISPR to create three changes to the genetic code of the donated cells so that they were less likely to have an immune response.

Two of these edits reduced the levels of proteins on the surface of the cells that signal to our white blood cells about whether a cell is foreign or not. A third edit boosted production of a protein that discourages attack from other immune cells called CD47.

The genetically edited cells were then injected into the man’s forearm. His body left the modified cells alone and the surviving cells produced insulin as normal.

Although the man was given a low dose of the edited cells and will still require daily insulin treatment, the case suggests that the procedure can be done safely.

The researchers’ next step is to carry out follow-up studies to find out whether the cells can survive in the long-term, which would make management of the disease easier and potentially provide a cure. They also need to do further tests to determine whether the approach works in other patients.

Hibernating mammals rely on particular genes to adjust their metabolisms as they enter that unique, low-energy state — and humans actually carry that same hibernation-related DNA.

Now, early research hints that leveraging this particular DNA could help treat medical conditions in people, scientists say.

Hibernation offers "a whole bunch of different biometrically important superpowers," senior study author Christopher Gregg, a human genetics professor at the University of Utah, told Live Science.

For example, ground squirrels can develop reversible insulin resistance that helps them rapidly gain weight before they hibernate but starts fading as hibernation gets underway. A better understanding of how hibernators flip this switch could be useful for tackling the insulin resistance that characterizes type 2 diabetes, Gregg suggested.

Hibernating animals also protect their nervous systems from damage that could be caused by sudden changes in blood flow. "When they come out of hibernation, their brain is reperfused with blood," Gregg said. "Often that would cause a lot of damage, like a stroke, but they've developed ways to prevent that damage from happening."

Gregg and his colleagues think tapping into hibernation-related genes in people could unlock similar benefits.

Related: Best-ever map of the human genome sheds light on 'jumping genes,' 'junk DNA' and more

A 'hub' of hibernation genes

In a pair of studies published Thursday (July 31) in the journal Science, Gregg and his team pinpointed key levers that control genes related to hibernation, showing how they differ between animals that hibernate and those that don't. Then, in the lab experiments, they delved into the effects of deleting these levers in lab mice.

Although mice don't hibernate, they can enter torpor — a lethargic state of decreased metabolism, movement and body temperature that typically lasts for less than a day — after fasting for at least six hours. This made mice a suitable genetic model for studying these effects.

Using the gene-editing technique CRISPR, the scientists engineered mice with one of five conserved noncoding cis elements (CREs) deactivated, or "knocked out." These CREs act as levers to control genes that, in turn, code for proteins that carry out biological functions.

The CREs targeted in the study lie near a gene cluster called the "fat mass and obesity-related locus," or the FTO locus, which is also found in humans. Gene variants found within the cluster have been tied to an elevated risk of obesity and related conditions. Broadly speaking, the FTO locus is known to be important for controlling metabolism, energy expenditure and body mass.

By knocking out the CREs, the researchers were able to change the mice's weights, metabolic rates and foraging behaviors. Some deletions sped up or slowed down weight gain, others turned metabolic rate up or down, and some affected how quickly the mice's body temperatures recovered after torpor, the researchers said in a statement.

This finding is "highly promising," particularly given the FTO locus plays a well-known role in human obesity, Kelly Drew, a specialist on hibernation biology at the University of Alaska Fairbanks, told Live Science in an email.

Knocking out one CRE — called E1 — in female mice caused them to gain more weight on a high-fat diet than did a comparison group with all of their DNA intact. Deleting a different CRE, called E3, changed the foraging behavior of both male and female mice, specifically changing how they searched for food hidden in an arena.

"This suggests that important differences in foraging and decision processes may exist between hibernators and non-hibernators and the elements we uncovered might be involved," Gregg said.

Unknowns to address

The study authors said their results could be relevant to humans, since the underlying genes don't differ much between mammals. "It's how [the mammals] turn those genes on and off at different times and then for different durations and in different combinations that shape different species," Gregg said.

However, "it's definitely not as simple as introducing the same changes in human DNA," Joanna Kelley, a professor who specialises in functional genomics at the University of California, Santa Cruz, told Live Science in an email. "Humans are not capable of fasting-induced torpor, which is the reason why mice are used in these studies," said Kelley, who was not involved in the work.

She suggested that future work include animals incapable of torpor, and focus on unpacking all the downstream effects of the deleted CREs. As is, the current study "definitely points the field in a new direction" in terms of how scientists understand the genetic controls driving changes in hibernators throughout the year, she added.

Drew also highlighted that torpor in mice is triggered by fasting, while true hibernation is triggered by hormonal and seasonal changes and internal clocks. So while the CREs and genes the study identified are likely critical parts of a metabolic "toolkit" that responds to fasting, they may not be a "master switch" that turns hibernation on or off.

"Nevertheless, uncovering these fundamental mechanisms in a tractable model like the mouse is an invaluable stepping stone for future research," Drew said.

Gregg emphasized that much remains unknown, including why the effects of some deletions differed in female mice versus male mice or how the changes in foraging behavior seen in mice might manifest in humans. The team also plans to research what would happen if they deleted more than one hibernation-linked CRE at a time in mice.

Down the line, Gregg thinks it could be possible to tweak the activity of humans' "hibernation hub genes" with drugs. The idea would be that this approach could yield the benefits of that gene activity — like neuroprotection — without patients having to actually hibernate, he said.

Early data hint that the common diabetes drug metformin may greatly reduce the risk of a severe form of morning sickness that affects thousands of pregnant people each year.

This form of morning sickness — called hyperemesis gravidarum (HG), or hyperemesis — can lead to complications during pregnancy, such as weight loss, dehydration and electrolyte imbalance, as well as long-term health issues for both mother and baby. It's also common for people who had hyperemesis in their first pregnancy to experience it again in subsequent pregnancies.

Previous research had established that people who are genetically predisposed to hyperemesis often have lower levels of a hormone called "growth and differentiation factor 15" (GDF15) prior to pregnancy. During pregnancy, the placenta makes GDF15, which is beneficial to the survival and growth of the fetus. Having low pre-pregnancy GDF15, the theory goes, makes individuals more sensitive to the hormone's rapid rise in pregnancy, triggering extreme nausea and vomiting.

Meanwhile, metformin, a drug commonly used to treat type 2 diabetes, is known to raise levels of GDF15 in all users, and this is thought to reduce appetite and promote weight loss. Knowing this link to GDF15, researchers explored whether metformin could "train" the body to tolerate the hormone before pregnancy.

Their survey-based study, published June 27 in the American Journal of Obstetrics and Gynecology, showed that when taken before pregnancy, metformin reduced the risk of hyperemesis by more than 70%.

If confirmed through further studies, this approach to hyperemesis prevention "would be a game changer," said Dr. Andrew Housholder, an emergency physician specializing in hyperemesis who was not involved in the study.

Related: We may finally understand how metformin lowers blood sugar, animal study finds

"HG patients often change their family planning due to the severity of their illness with prior pregnancies," Housholder told Live Science in an email. "Allowing a person to have a normal pregnancy, without the severe symptoms and weight loss, is very meaningful."

For the study, researchers recruited more than 5,400 participants who visited the Hyperemesis Gravidarum Education and Research Foundation's social media platforms. These people were asked to fill in an online questionnaire. Respondents reported their daily use of 32 common substances, including prescribed medications and recreational drugs, in the month before each pregnancy, along with their level of nausea and vomiting during pregnancy.

Metformin use before pregnancy was linked to a more than 70% reduction in the risk of hyperemesis in first pregnancies and an 82% risk reduction in second pregnancies, the survey suggested. Additionally, tobacco use before pregnancy was associated with a 49% lower risk of experiencing hyperemesis — although the drug of course ups the risk of other serious pregnancy complications.

In contrast, pre-pregnancy use of selective serotonin reuptake inhibitors (SSRIs), a common class of antidepressants, was associated with increased risk of hyperemesis in both first and second pregnancies. Cannabis use was associated with increased risk in only second pregnancies.

"The large reduction in risk [tied to metformin] identified provides strong evidence to support that pre pregnancy metformin treatment can provide a benefit," study co-author Marlena Fejzo, a medical scientist at the Keck School of Medicine of the University of Southern California, told Live Science in an email.

While the findings are promising, they are based on self-reported data in a highly selective population, noted Dr. Stephen O'Rahilly, a professor of clinical biochemistry and medicine at the University of Cambridge in the U.K. who was not involved in the study. A clinical trial is now needed to confirm whether prescribing metformin before pregnancy could effectively prevent hyperemesis, O'Rahilly told Live Science in an email.

Clinical trials will also need to measure how the dose of metformin and timing of administration impacts outcomes, study co-author Dr. Aimee Brecht-Doscher, an OB/GYN physician at Ventura County Health Care Agency in California, told Live Science in an email.

Metformin is safe to take during pregnancy and many users take it throughout pregnancy to treat diabetes, Brett-Doscher noted. But notably, the study didn't look at what effect the drug might have on morning sickness at that juncture or how many participants went off the medication post-conception.

For people who don't already take metformin prior to pregnancy, it may be that the drug would come too late to help stave off hyperemesis. However, it could theoretically be used to prevent hyperemesis in subsequent pregnancies. But again, this would need to be confirmed in trials.

"Women who've had HG once are likely to have it again," Brecht-Doscher said. "Many, having been traumatized by the experience, decide they'll never again get pregnant. Using metformin to reduce the chances of a recurrence could give them more options."

"This study clears the way for clinical trials, because we've shown it's worth pursuing," she added.

This article is for informational purposes only and is not meant to offer medical advice.

Semaglutide, the active ingredient in Ozempic, and other drugs in the same class have revolutionized the treatment of obesity and type 2 diabetes. Now, a clinical trial suggests the medicines can treat type 1 diabetes, as well.

The trial results, published June 23 in the journal NEJM Evidence, suggest semaglutide can improve blood sugar levels and induce weight loss in people with type 1, potentially introducing a new drug that could be used along with insulin to manage the disease.

"For a hundred years, we are fixated on insulin and insulin delivery … and there aren't really extra medications that are approved for type 1," lead study author Dr. Viral Shah, a diabetes researcher at Indiana University, told Live Science. There are some add-on drugs approved for use alongside insulin, but Shah envisions Ozempic-like drugs as a potential firstline treatment.

The insulin resistance and impaired release of digestive hormones that fuel type 2 diabetes can also exist in type 1, so it does make sense to explore treatments for those, he said.

Type 1, type 2, and double diabetes

Type 1 and type 2 diabetes are driven by very different mechanisms.

In type 2, cells in the pancreas that make insulin become less sensitive to blood sugar and produce less insulin in response. Insulin normally helps usher sugar from the bloodstream into cells, so this effect causes sugar to build up in the blood. Meanwhile, type 1 diabetes is an autoimmune disorder in which the insulin-secreting cells are destroyed by one's own immune system.

Related: In a 1st, scientists reversed type 1 diabetes by reprogramming a person's own fat cells

There are several drugs for type 2 diabetes that focus on driving cells to secrete more insulin, and there are standard treatments centered around improving blood sugar control, weight loss, high blood pressure and cardiovascular disease risk through lifestyle changes. Drugs like semaglutide, known as GLP-1 agonists, control blood sugar in type 2 by reducing a liver-made hormone that raises blood sugar, as well as slowing down digestion. This makes you feel fuller for longer and allows the pancreas more time to release the right amount of insulin.

The primary way to control blood sugar in type 1 diabetes, however, is insulin replacement. But type 1 diabetics, especially those with obesity, often have insulin resistance and thus many of the same health issues as those with type 2 — for example, nerve damage, foot ulcers and eye damage, all due to uncontrolled blood sugar. This condition has been termed "double diabetes."

"Type 1 diabetes does not exclude the presence of type 2 diabetes," Shah said. "People with the double diabetes phenotype may benefit from some of the medications that are currently approved for type 2 diabetes." That was the idea behind the new trial of semaglutide, the ingredient found in the weight-loss drug Ozempic and type 2 diabetes drug Wegovy.

The researchers recruited 72 patients with type 1 diabetes and obesity, based on their BMIs. Half the participants received a weekly semaglutide injection and the other half a placebo for 26 weeks. All the participants continued using insulin as needed throughout the trial, and their blood sugar was monitored using continuous glucose monitors.

The patients taking semaglutide had better control over their blood sugar levels, staying within an acceptable range of blood sugar levels over 70% of the time while also spending less time with low blood sugar levels. The treated individuals also lost at least 5% of their body weight. But no one in the untreated group met all three of these criteria.

These results support findings from other recent trials, showing that these drugs used for type 2 diabetes are worth exploring in type 1 diabetics, said Ahmad Haidar, a diabetes researcher at McGill University in Canada, who was not involved in the study.

"It's an important study that adds to the existing evidence toward the safety and efficacy of the use of semaglutide in type 1, but it is not enough," Haidar told Live Science. "We need more evidence to help these drugs be approved by regulatory agencies."

Shah and his colleagues hope that with more clinical trials with bigger cohorts of patients, the research community will gather enough evidence to have this use of GLP-1s approved by the Food and Drug Administration and added into the American Diabetes Association standards of care for type 1. If approved, the treatments could then potentially be covered by health insurance.

"And if that happens, I think this would be probably the first drug beyond insulin for people with type 1 diabetes to use," Shah said. "It's really exciting that it's moving forward."

This article is for informational purposes only and is not meant to offer medical advice.

The patient: A 31-year-old woman in the U.K.

The symptoms: The patient had a history of type 1 diabetes, mild learning difficulties and end-stage kidney failure. For the last condition, she was receiving dialysis three times a week.

This treatment fills in for the kidneys by clearing waste and excess fluid from the bloodstream, and patients are advised to restrict their fluid and salt intake between sessions. If they don't, fluid can build up in the body because the kidneys aren't filtering it out of the blood, leading to weight gain and strain on the heart.

In this case, the woman consistently experienced this excessive fluid buildup between appointments, "despite several interventions" aimed at helping her manage it.

What happened next: Over time, the patient could no longer tolerate long dialysis sessions, so she would start and end each session above her target weight due to all the fluid buildup. She also reported experiencing occasional constipation.

After one dialysis session, a nurse cleaning the chair the woman had been sitting in noted that it felt "rather light." Upon inspection, she noted large chunks of foam — specifically low-density polyurethane foam — were missing from the chair.

The diagnosis: The woman's medical team discovered this was a case of pica, in which people develop a habit or compulsion to eat non-food items.

"We were surprised to discover that our patient had been eating the foam and had increased her fluid intake with the assumption that it would absorb excess water in the stomach and thus prevent systemic absorption," her doctors wrote in a report. "This was evidently not the case." In other words, she hoped the foam would act like a sponge and soak up the excess fluid she was retaining.

Pica is sometimes associated with nutrient deficiencies, such as a lack of iron or zinc, leading some scientists to theorize that these deficiencies lead to unusual cravings. Alternatively, some think that people with pica may be drawn to the sensations — the tastes, textures or smells — of non-food substances. The condition is sometimes associated with pregnancy or sickle cell anemia, as well as certain mental health disorders and medications.

In this case, the woman’s doctors ran tests and ruled out nutritional deficiencies as a factor. They also didn't uncover any "acute psychosocial triggers for her behaviour," and she had no past history of pica. They suspected that her known learning difficulties may have played a role.

The treatment: The patient was advised about the consequences of eating foam and received regular guidance from a dietitian with a speciality in helping patients with kidney dysfunction. Her family also became more closely involved in her treatment. Other cases of pica are typically treated with behavioral therapies, but the case report didn't note whether any such options were explored.

She additionally received a laxative treatment to help her pass the foam she'd already eaten without any complications. At the time the case report was published in 2010, she was continuing to undergo dialysis three times a week.

What makes the case unique: Cases of pica have been reported among kidney disease patients in the past, but they typically involve patients craving and eating clay, dirt, aspirin, flour, baking soda or ice. The effects can range from benign to severe; in the latter case, a person may experience toxic effects, dental problems, bowel obstruction or malnutrition, for example.

The woman's doctors searched the medical literature for cases of kidney disease patients eating polyurethane foam and didn't find any, but they did find a few cases of people without renal disease eating the material.

"This case highlights a recognised but under-diagnosed phenomenon in renal patients, known as pica," the doctors wrote. "While the ingestion of ice, aspirin, clay and baking soda has been reported in haemodialysis patients, this case is unique in that the patient resorted to eating foam from her dialysis chair."

This article is for informational purposes only and is not meant to offer medical advice.

An experimental pill may work just as well as injectable, Ozempic-style drugs at treating type 2 diabetes, early trial results suggest.

The oral medication, called orforglipron, belongs to a class of drugs called glucagon-like peptide 1 (GLP-1) agonists. This class also includes Ozempic, which is made by Novo Nordisk and approved as a blood-sugar control aid in type 2 diabetes, as well as a treatment for people with type 2 and either heart disease or kidney disease. It also includes Wegovy, which has the same active ingredient as Ozempic but is approved for chronic weight management.

GLP-1 agonists are best known as weight-loss drugs, and likely drive weight loss in part by slowing digestion and curbing appetite by messing with hunger signals in the body. In diabetes, the drugs help lower blood sugar by boosting levels of insulin, the hormone responsible for shuttling sugar out of the blood.

However, as of yet, GLP-1s are all injectable medications that require refrigeration, The New York Times reported. It's possible that introducing a daily pill that can achieve the same results could potentially increase the availability and use of the medications, Lilly, the drug's maker, suggests.

Related: Ozempic-style drugs tied to more than 60 health benefits and risks in biggest study-of-its-kind

"Injections cannot be the solution for billions of people around the world," Dr. Daniel Skovronsky, chief scientific officer of Lilly, told The New York Times.

In a statement published Thursday (April 17), Lilly shared the topline results of a late-stage trial of orforglipron. The trial's results have not yet been published in a scientific journal but will be in the future, and the results will also be presented at the American Diabetes Association's 85th Scientific Sessions, the statement noted.

The trial included 559 adults with type 2 diabetes whose blood sugar was not adequately controlled with diet and exercise alone. For just over nine months, the participants took either orforglipron or a placebo pill daily. Those taking orforglipron got one of three doses: 3 milligrams, 12 mg or 36 mg.

After 40 weeks, the trial runners checked everyone's blood sugar levels using an A1C test, which can reveal average blood-sugar levels from the preceding three months. The test gives results as a percentage, with 6.5% or higher typically indicating diabetes and 5.7% to 6.4% signaling prediabetes. The participants in the trial started out with an average A1C of 8%.

After 40 weeks, the groups who took orforglipron saw their A1C drop by 1.3% to 1.6%, on average, while the placebo fell only 0.1%. That effect is about the same as what was seen in separate trials of Ozempic and Mounjaro, another GLP-1, The New York Times reported.

Around two-thirds of those who took the highest dose of the drug had their levels fall to less than or equal to 6.5%, the threshold for diabetes. The high-dose group also lost an average of 16 pounds (7.3 kilograms) each. The other dosing groups lost about 10 to 12 pounds (4.4 to 5.5. kg), while the placebo group lost about 3 pounds (1.3 kg).

"Given that participants had not yet reached a weight plateau at the time the study ended, it appears that full weight reduction was not yet attained," the Lilly statement noted.

The most common side effects were mild to moderate and were similar to those seen with other GLP-1s. For example, diarrhea, nausea, indigestion, constipation and vomiting were more common in the treatment groups than the placebo. Between 3% and 8% of the participants in each treatment group opted to stop taking the medication, compared to 1% of the placebo.

Lilly said it would seek approval from the Food and Drug Administration later this year to market orforglipron for obesity and early in 2026 for diabetes, The New York Times reported. In addition to the diabetes trial described above, the company is also testing the pill in adults with obesity or who are overweight with at least one weight-related medical problem. They're also investigating its use as a treatment for high blood pressure and sleep apnea in people with obesity.

The price of the pill has not yet been announced.

This article is for informational purposes only and is not meant to offer medical advice.

Five scientists who helped develop Ozempic-style drugs have been awarded a $3 million prize nicknamed the "Oscars of Science."

The Breakthrough Prizes are annual awards that aim to recognize "the world’s top scientists working in the fundamental sciences," according to the official website for the prizes. Six awards are given, in total, covering accomplishments in fundamental physics, mathematics and the life sciences.

This year, Dr. Jens Holst, Dr. Daniel Drucker, Dr. Joel Habener, Lotte Knudsen and Svetiana Mojsov have been announced as joint winners of one of three Breakthrough Prizes in Life Sciences for 2025.

"When something [like this award] drops in completely unexpected, that's nice, that's wonderful," Holst, a professor of medical physiology at the University of Copenhagen, told Live Science.

Related: Scientists behind tech in mRNA vaccines snag 2nd prestigious prize — is a Nobel next?

Holst and his colleagues received one of the life-science awards this year "for the discovery and characterization of glucagon-like peptide 1 and revealing its physiology and potential in treating diabetes and obesity," read an official statement.

Glucagon-like peptide 1, or GLP-1, is a hormone that the gut secretes after eating. The hormone stimulates the release of insulin, which lowers blood sugar levels, and it also slows down digestion, making people feel full. It's a key player in how the brain regulates appetite.

Drugs like Ozempic and Wegovy are examples of "GLP-1 receptor agonists" — they mimic the action of the GLP-1 hormone in the body to treat type 2 diabetes and obesity, respectively.

These drugs have garnered significant popularity over the past decade, and they are now being investigated as potential treatments for many other health conditions, ranging from substance-use disorders to Alzheimer's disease. In 2024, Wegovy also got regulatory approval in the United States to treat heart disease, although questions remain regarding how it actually treats the condition.

However, despite their success, GLP-1 receptor agonists have also faced considerable scrutiny. For instance, there have been reports of some patients experiencing nasty side effects, such as persistent vomiting and stomach paralysis.

Additionally, a large study published in 2025 revealed that these drugs may reduce the risk of developing 42 health conditions but may increase the chances of experiencing 19 others, including abdominal pain, low blood pressure and arthritis. This study was correlational, so it's unknown if GLP-1 agonists are actually driving these conditions, but it still raises questions about the drugs' long-term effects.

Even with these concerns, though, many believe these drugs have revolutionized the treatment of cardiometabolic disorders. In the U.S., 1 in 8 adults have reported using a GLP-1 drug at some point in their lives.

Holst and colleagues originally discovered the GLP-1 hormone back in the 1980s. Piece by piece, they gathered data showing that the hormone stimulated insulin secretion, and that it inhibited food intake and the emptying of the stomach after a meal, Holst said.

Over the years, the researchers further examined these physiological effects within the context of diabetes and obesity, which eventually led to the development of the widely used drugs that are household names today.

There is likely a huge interest around these drugs because they offer an alternative, and very effective, route to weight loss for people with obesity who might not have found success with other interventions, Holst said. However, as a doctor, he is more interested in their ability to treat the knock-on health concerns tied to obesity, such as certain cancers and atherosclerosis, which can lead to coronary artery disease, he added.

"What we know is that obesity is associated with a hell of [a lot of] complications," he said. "The important thing is that with these compounds, you can prevent that."

Holst and colleagues are now investigating how the body regulates its own GLP-1 hormone levels and whether this process can be manipulated. For instance, they want to see whether patients with obesity or diabetes could be given a drug that increases the secretion of their own GLP-1 hormone, rather than being given a drug that just mimics the action of GLP-1, Holst said.

In addition to the prize awarded to GLP-1's developers, the other two life sciences awards this year went to Dr. Stephen Hauser and Dr. Alberto Ascherio, for their work on multiple sclerosis, and David Liu for developing two common gene editing technologies known as "base editing" and "prime editing."

This year's winners will receive their awards at a ceremony in Los Angeles on April 5, 2025.

Since the 1990s, doctors have prescribed the drug metformin to treat type 2 diabetes, but scientists didn't fully understand how it worked.

Now, new research fills in one piece of the puzzle: Metformin triggers the body to expel glucose from the bloodstream into the intestines, where bacteria feed on the carbohydrate to make compounds that may help control blood sugar levels.

In the new study, published March 3 in the journal Communications Medicine, researchers calculated that metformin treatment increased how much glucose was released into the gut nearly fourfold. That seemed to boost the production of fatty compounds that help protect the gut and reduce inflammation.

Multiple pathways

Most research has focused on metformin's effects in the liver, where it boosts how cells respond to insulin and blocks the synthesis of the sugar glucose. But some studies have suggested that the drug also acts on the gut, perhaps by blocking glucose uptake into the bloodstream.

"Many people are working on the gut action of metformin because if you take metformin orally, the intestines are exposed to very high concentrations," said senior study author Dr. Wataru Ogawa, a medical researcher at Kobe University in Japan. (Ogawa received research support and lecture fees from the metformin manufacturer Sumitomo Pharma.)

Previously, Ogawa's team showed that the body excretes glucose into the hollow tunnel of the human gut where food and waste travel, known as the lumen. This happens in people with and without diabetes. "It means that this is a physiological function that humans have," Ogawa told Live Science.

Related: Ozempic-style drugs tied to more than 60 health benefits and risks in biggest study-of-its-kind

Feeding gut bacteria

In the new study, the researchers found that metformin nearly quadrupled the rate of glucose excretion into the gut in five people with type 2 diabetes, and they replicated those findings in mice.

Keeping glucose out of circulation by directing it to the gut might directly lower blood sugar levels, but scientists told Live Science they think this explains only part of metformin’s therapeutic effects.

Nicola Morrice, a metformin researcher at the University of Dundee in Scotland who was not involved in the study, told Live Science in an email, "I do not expect this to be the drug's main mechanism of action."

Besides drawing sugar out of the bloodstream, excreted glucose could also have an indirect effect on blood sugar by feeding gut bacteria, other experts told Live Science.

Dr. José-Manuel Fernández-Real, a medical researcher at the University of Girona in Spain who was not involved in the study, told Live Science in an email, "Some bacteria, particularly those that thrive on simple sugars, may experience increased growth, while others that rely on complex carbohydrates or fiber fermentation might be less affected."

A glucose molecule has a backbone of six carbon atoms, so to determine the rate at which gut bacteria break down glucose into other molecules, Ogawa had to find a way to keep track of these carbons. His team injected mice with glucose containing a "heavy" isotope, meaning a version of carbon that carries an extra neutron. This allowed them to trace the heavy carbons as the bacteria transformed glucose into other compounds.

Stool samples revealed that bacteria in mice treated with metformin had converted the heavy glucose into short chain fatty acids (SCFAs). "Bacterial species that produce short chain fatty acids are generally 'good' bacteria," suggesting metformin’s effects could potentially foster a healthy microbiome, Ogawa said.

Metformin treatment caused SCFAs containing heavy carbon to increase by just 1% in stool samples. However, Manuel Vázquez-Carrera, a pharmacology researcher at the University of Barcelona who was not involved with the study, told Live Science in an email that "most SCFAs are rapidly absorbed and utilized rather than excreted." That means the measurement was likely an underestimate.

And "even a slight rise in SCFA production could enhance gut barrier function, reduce inflammation, and improve insulin sensitivity, all of which are beneficial for managing diabetes," Fernández-Real speculated.

The study had a few limitations. First, the researchers did not assess how higher levels of gut SCFAs affected the health of the mice. It also included "a very small number of participants who were receiving varying doses of metformin as part of their treatment regimes," Morrice said.

The mouse work also involved only male rodents, so possible sex differences in the drug's actions were not explored. Beyond testing metformin's effects on five diabetes patients, Ogawa said he has finished a larger, gold-standard trial in humans to further study the drug's impacts on the gut. The researchers haven't completed the analysis, but as of yet, they haven't seen any sex differences.

Morrice suggested that future work could explore how metformin affects glucose excretion in mice that consume different diets, such as high-fat, high-sugar diets, which are linked to obesity.

This article is for informational purposes only and is not meant to offer medical advice.

Scientists have identified neurons in an evolutionarily ancient part of the brain that control when you stop eating a meal — at least in rodents.

The researchers discovered that cholecystokinin (CCK) neurons — which are found in the brain stem, one of the oldest parts of the brain — integrate various signals produced as we eat, causing us to feel full and not want to take another bite. The scientists described their findings in a new study published Wednesday (Feb. 5) in the journal Cell.

The feeding signals these neurons respond to relay information like how much food is detected by receptors in the mouth; how full the stomach is; and how high the levels of different "hunger-signalling hormones" in the blood are. These hormones rise and fall in response to food consumption and metabolism.

The new research is still in its early stages, having only been conducted in mice so far. However, the human brain stem is fairly similar to that of mice, so it's likely that the same control mechanism occurs in our brains too, the study authors said.

Related: Does it really take 20 minutes to realize you're full?

Different cell types in the brain regulate various aspects of feeding behavior, such as hunger and satiation, study lead author Srikanta Chowdhury, an associate research scientist at Columbia University Vagelos College of Physicians and Surgeons, told Live Science in an email. Satiety refers to the feeling of fullness and satisfaction after a filling meal.

For instance, some neurons in part of the brain called the hypothalamus detect when metabolism levels are low and stimulate feelings of hunger to promote food intake, while other neurons regulate jaw movements while we eat, he said. But until now, little was known about how the brain senses the amount of food we're eating in real time to regulate how much more we consume, he noted.

The team focused on the brain stems of mice to build on research in rodents dating back to the 1970s, which hinted that the brain stem could play a role in regulating feelings of fullness. However, which particular cells within this region did this and and how was unclear.

To see how CCK neurons may influence eating, the scientists genetically modified mice so that their CCK neurons could be switched on and off using light in lab experiments. They found that when these neurons were activated, the mice ate smaller meals compared to unmodified mice, and the extent of activation determined how quickly the modified mice stopped eating.

The findings suggest that CCK neurons regulate how much mice eat during a given meal, the team concluded.

If equivalent neurons are found in the human brain stem, the findings could theoretically lead to the development of new treatments for conditions like obesity.

This idea was supported by separate experiments conducted in the same study, in which the team discovered that mouse CCK neurons can be activated by a drug called exendin-4, which caused the mice to stop eating. Exendin-4 is in the same class of drugs as Ozempic and Wegovy, which are becoming increasingly popular for the treatment of type 2 diabetes and obesity, respectively.

"Whether used alone or alongside other medical interventions, these findings could provide a pathway for clinically regulating eating behavior and possibly for developing weight-reducing drugs," Chowdhury said. But again, these findings in rodents must first be extended to people.

Weight-loss drugs like Ozempic may decrease your risk of developing 42 health conditions, but increase your chance of experiencing 19 others, according to one of the most comprehensive studies-of-its-kind to date.

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have become increasingly popular over the past decade for the treatment of type 2 diabetes and obesity, with versions like Ozempic and Wegovy becoming household names.

These drugs help treat diabetes by promoting the release of insulin and helping to reduce blood sugar levels. But they have also been linked to weight loss, potentially by slowing down the digestion of food and curbing appetite. In 2024, Wegovy also received regulatory approval in the U.S. to treat heart disease, although the exact mechanism-of-action is unclear.

Evidence is additionally emerging to suggest that GLP-1RAs may help prevent the onset of conditions such as Alzheimer's disease and help patients to manage others like substance-use disorders. However, concerns have also been raised regarding the negative side effects of taking GLP-1RAs, including reports of gastrointestinal issues.

Related: Ozempic-like meds linked to higher risk of pancreatitis, 'stomach paralysis' than other weight-loss drugs

Now, in a new study, scientists have compiled what they say is the clearest ever picture of the effectiveness and risks associated with taking GLP-1RAs.

In the study, researchers assessed the impact of taking GLP-1RAs on the health of 215,000 people with type 2 diabetes over around four years. They then compared these effects to a control group of more than one million individuals who received different types of anti-diabetic drugs. Data on all participants was obtained from the U.S. Department of Veteran Affairs.

Overall, the researchers found that GLP-1RAs have many beneficial effects, some of which were previously recognized. For instance, those who took GLP-1RAs had a 9%, 8% and 12% reduced risk of having a heart attack, deep vein thrombosis and Alzheimer's, respectively, compared to controls. They were also less likely to develop substance-use disorders, including alcohol-use disorders and cannabis-use disorders (both an 11% lower risk), as well as having a 12% lower risk of experiencing bacterial infections.

These effects may somehow be linked to both the health benefits of physically losing weight, as well as other effects of GLP-1RAs in the body, such as reducing inflammation and influencing reward signaling in the brain, Dr. Ziyad Al-Aly, study co-author and an assistant professor of medicine at Washington University, said during a Jan. 16 news conference.

However, these benefits did not come without risks, the researchers observed. For example, GLP-1RAs also increased people's odds of developing gastrointestinal issues such as abdominal pain (12%), plus low blood pressure (6% higher risk) and arthritis (11% higher risk).

"We tend to think of drugs as being surgically designed to do only one thing, but the reality is, it's almost never like this," Al-Aly said.

The study, which was published Monday (Jan. 20) in the journal Nature Medicine, mainly used data from older, white males, meaning that the findings may not apply to other demographics.

Nevertheless, the hope is that healthcare providers could use the findings to decide whether patients should take these drugs, depending on their medical history, Al-Aly said.

"This [study] is a great example of the value of large databases of medical records data enabling not only a study to assess safety profile but also potential new uses for an increasingly widely used therapy for diabetes and obesity," Dr. Penny Ward, a visiting professor in pharmaceutical medicine at King's College London who was not involved in the research, told Live Science in an email.

The study was observational, therefore it cannot prove that GLP-1RAs cause these effects. To do this, a randomized controlled trial is needed, whereby the effects of GLP-1RAs are tested against a control group in a tightly-regulated way.

Fortunately, such trials are currently underway with results potentially available in the next one to four years, said Dr. Naveed Sattar, a professor of cardiometabolic medicine at the University of Glasgow in Scotland, who was not involved in the research.

"Such trials will lead us much closer to the truth," he told the U.K. Science Media Centre.

This article is for informational purposes only and is not meant to offer medical advice.

In a first, scientists have designed immune cells that protect stem cell transplants from being rejected by the body — and they could someday open the door for a cure for diabetes.

The new cells, which were able to protect insulin-producing cells transplanted into mice, are an early "proof-of-concept," said study co-author Audrey Parent, an associate professor at the University of California, San Francisco (UCSF) Diabetes Center.

But if shown to be safe and effective in people, the designer cells could one day be used to protect transplanted tissues from attack, reducing or eliminating the need for drugs that suppress the immune system. That, in turn, could pave the way to a cure for diseases like type 1 diabetes.

In type 1 diabetes, immune cells, known as killer T cells, destroy pancreatic beta cells, which make insulin. In recent years, scientists have progressively inched closer to replacing destroyed beta cells with new cells derived from stem cells, which can be made to turn into any type of cell in the body.

Related: 'Like a reset button on a computer': Designer cells 'reboot' immune system in 3 different autoimmune diseases

In June, for instance, scientists reversed type 1 diabetes in a person by reprogramming their fat cells, while the Boston-based company Vertex Pharmaceuticals recently launched a pivotal, large-scale trial testing whether reprogrammed stem cells can eliminate the need for insulin in those with type 1 diabetes.

But before such stem-cell transplants can be widely used, scientists need to solve one big problem: In type 1 diabetes, killer T cells have been trained to target beta cells and have already destroyed those cells once. The transplanted cells need protection from this immune attack, so for now, patients need strong drugs that suppress the immune system. However, these drugs leave patients open to dangerous infections and are toxic to the kidneys and other organs.

To get around this problem, Parent and colleagues engineered T cells in the lab that protected the transplanted cells — known as a graft — from attack.

"We took an immune cell and changed the machinery inside it to make it a protective cell instead of a killer cell," Parent told Live Science. "And then we targeted it to the graft." Essentially, the designer cells act as bodyguards.

The bodyguards zero in on beta cells because they recognize a specific protein, called CD19, that the researchers added to the beta cells. When the bodyguard cells grab onto CD19, they then crank out a molecule that inhibits killer T cells.

The guards also make a protein that sops up an inflammatory chemical that normally helps activate killer T cells. This anti-inflammatory protein also tells the guards to replicate, creating a positive feedback loop that reinforces their ranks, Parent said.

To test their guards in a living organism, the researchers then took beta cells derived from stem cells and implanted them into mice. They then sent killer T cells to attack the transplanted beta cells. In one group of mice, they also injected their designer cells to defend the transplants.

In the mice not given designer cells, the killer cells quickly wiped out all the beta cells. But in the mice injected with designer cells, the transplants lived at least 35 days, and the mice were still producing insulin at that time, researchers reported in the study, published Thursday (Dec. 5) in the journal Science.

The results show it is possible to engineer T cells that can protect transplanted tissue, Parent said.

However, one challenge is finding a unique protein target to activate the designer cells, Parent said, as most potential targets are found on cells in multiple places in the body. That raises the chances that their designer cells will activate elsewhere in the body, beyond the transplants. That could pose a problem if, for instance, cells with the protein target become infected or cancerous, but can't be cleared because they are being protected by the guard cells. Transplant cells could be engineered to have a "kill" switch for those cases, but other cells in the body wouldn't have this switch.

Follow-up work may address this problem. For instance, the team could engineer an artificial target that would be found only on the transplanted beta cells and nowhere else, study co-author Wendell Lim, a biochemist and director of the UCSF Cell Design Institute, told Live Science in an email.

In a separate study, also published Thursday in Science, Lim and colleagues showed that similar designer T cells could target brain tumor cells while leaving healthy brain cells alone. The cells could also deliver anti-inflammatory chemicals to brain cells in mice with a disease similar to multiple sclerosis.

Looking forward, the team is also interested in seeing how this approach works against other autoimmune diseases fueled by inflammation, such as rheumatoid arthritis, as well as Crohn's disease and other inflammatory bowel diseases, Lim added. But it will be several years before these ideas can be tested in humans, he said.

"This work opens up a new avenue for treating inflammatory diseases in a targeted way," he said," but lots of pieces need to be put together and tested to come up with effective therapies."

Ever wonder why some people build muscle more easily than others or why freckles come out in the sun? Send us your questions about how the human body works to community@livescience.com with the subject line "Health Desk Q," and you may see your question answered on the website!

For the first time, scientists in China reprogrammed a woman's fat cells to turn them into insulin-making pancreatic cells that reversed her type 1 diabetes.

The feat adds to a growing body of evidence that reprogrammed stem cells could one day be used to treat or cure the chronic disease. The patient treated in the recent study still doesn't need any injected insulin a year out from her procedure.

These findings are "very exciting," said Dr. Kevan Herold, the C.N.H. Long professor of immunobiology and of medicine at Yale School of Medicine, who was not involved in the research.

Insulin is the chemical key that allows sugar molecules to exit the bloodstream and enter cells, where they can be used for fuel. In type 1 diabetes, however, the immune system destroys the body's insulin-producing cells, which are nestled within larger "mini-organs" within the pancreas, called islets.

Related: Drug could reduce need for insulin in type 1 diabetes, early trial hints

Without insulin, cells are starved of fuel while blood sugar levels rise. In extreme cases, people die as the body churns out acidic compounds, known as ketones, in a bid to make enough energy for cells to survive.

In the new study, which was published Thursday (Oct. 31) in the journal Cell, scientists took fat cells from a patient with type 1 diabetes and used chemicals to revert them back into "pluripotent" stem cells, meaning they could turn into any type of cell.

After reverting the cells to this state, the scientists chemically coaxed them to become islet cells. These new islet cells were then implanted in the patient's abdomen.

Before undergoing this experimental treatment, the patient struggled to control her blood sugar, spending less than half her time in a "target" healthy blood sugar range, said study lead author Hongkui Deng, a researcher at the Peking-Tsinghua Center for Life Sciences at Peking University in Beijing. After the patient's cell transplant, her time in the target zone "improved to over 98%," Deng told Live Science in an email.

By 75 days after the transplant, the patient no longer needed to inject insulin to control her blood sugar.

"The rapidity with which the patient showed reversal of diabetes and achieved insulin independence after transplantation was surprising," Deng said. "This finding suggested remarkable potential of this therapeutic strategy.".

Transplanting islet cells into patients isn't a new approach. For three decades, scientists have harvested islets from donated bodies and then transplanted the cells into the livers of patients with type 1 diabetes. However, there are a limited number of donors, and transplant recipients must take strong drugs for the rest of their lives to suppress the immune system and prevent their new mini-organs from being rejected. As a result, only patients who need other transplants, such as kidney or liver transplants, typically receive donor islet cells.

The patient in the new study was no different in that respect. She had previously received a liver transplant and so was on strong immune-suppressing drugs. Nevertheless, the new kind of islet transplant she received marks an advance: Unlike cells from donated bodies, stem cells offer a potentially unlimited source of new islets.

The cells grafted into the belly did better than those implanted in the liver usually do, showing "markedly improved insulin secretion," Deng said. What's more, the abdomen is easily accessible and can be scanned using MRI. That means the implanted cells can be easily monitored for safety and removed if they start to fail, he added.

The new study is part of a growing body of evidence that islets derived from stem cells can reverse type 1 diabetes, at least for a time. For instance, Vertex Pharmaceuticals is developing embryonic-stem-cell-derived islets and has shown that these cells can normalize blood sugar levels, at least in the handful of patients tested so far.

While the new stem cell treatment may not face the traditional risks associated with organ rejection, the transplanted islets could still be targeted for destruction by the immune system. For this treatment to be appropriate for more patients with type 1 diabetes, scientists need to find a way to make stem cell transplants invisible to the immune system without the use of strong immunosuppressants.

Heart disease, cancer, diabetes — these and other concerning health effects have been tied to "ultraprocessed foods," which make up more than half of the calories consumed in the U.S. Eating large amounts of these foods, which are high in salt, sugars and additives, may even increase a person's risk of early death. 

There's growing awareness around the potential harms of these products, but which foods count as "ultraprocessed" is not always clear. 

So what, exactly, are ultraprocessed foods?

Related: What is brominated vegetable oil, and why did the FDA ban it in food?

Define 'ultraprocessed'

Almost all foods are processed in some way, but classification systems distinguish the types of processing they undergo. One commonly used system is the NOVA classification system, which categorizes food into four groups, Adrian Brown, a senior research fellow at University College London, told Live Science in an email. These include unprocessed and minimally processed foods, processed culinary ingredients, processed foods and ultraprocessed foods. 

Unprocessed foods include the edible parts of plants or parts from animals as they're found in nature — for example, fresh, whole heads of broccoli; unsalted seeds; mushrooms; and eggs. Minimally processed foods are slightly altered to make them more suitable or safe to consume, meaning they may be frozen, roasted or dried. Nothing is added to these foods, so they're free of salt, sugar or oil. Examples include frozen peas and roasted coffee beans. 

Next you have processed culinary ingredients, used to season and cook foods and obtained by slightly processing foods from the first group. For instance, vegetable oils can be derived from crushed seeds. 

Processed foods include smoked meats, canned vegetables, tofu and fresh breads. They contain multiple ingredients and increase a food's shelf life, generally by adding processed culinary ingredients, like salt. They're still considered versions of the original foods — for instance, packaged applesauce is made from whole apples.

Ultraprocessing, on the other hand, dramatically transforms ingredients through intensive, industrial methods.

NOVA defines ultraprocessed foods as "formulations of ingredients, mostly of exclusive industrial use, typically created by series of industrial techniques and processes." Examples of ingredients used only in industrial settings include specific sugars, such as dextrose,  and protein sources, such as casein.

Ultraprocessing involves breaking down foods into their component parts, such as starches and oils. These are then chemically modified — to break bonds between their molecules, for instance — and combined with techniques like extrusion, which forces soft substances together into a desired shape. Colors, flavors, emulsifiers and other additives are also used to enhance a food's taste and shelf life.

Ultraprocessed foods include soft drinks, candies, breakfast cereals, chicken nuggets, hot dogs and instant soup powders. They are meant to be convenient to prepare and tasty to consume.

Related: Risk of AFib tied to sugary and artificially sweetened drinks

Dangers of ultraprocessed foods

There are several reasons ultraprocessed foods are bad to eat in excess, Dr. Jennifer Hankenson, who practices physical medicine and rehabilitation at Yale Medicine, told Live Science in an email.

"One is because they have additives that are dangerous to our health and increase the risk of developing chronic health conditions such as diabetes, cancer, heart disease, and high blood pressure," Hankenson told Live Science. Ultraprocessed foods often have an excess of certain ingredients, such as sugar and salt, that make them highly palatable, making it harder for consumers to stop eating at suggested serving sizes, she said. 

The products are also low in fiber, so they're absorbed quickly in the gastrointestinal tract and don't adequately nourish the gut microbiome. In addition, evidence suggests they don't set off the same satiety signals as unprocessed foods do, leaving people feeling hungrier. 

Hankenson said eating small amounts of ultraprocessed foods likely isn't bad for you. However, she noted that no amount would be considered "healthy" or "recommended," per se, especially for people with chronic health conditions.

Erikka Loftfield, an investigator at the National Cancer Institute, said the organization recently conducted a study of more than 500,000 people that linked high ultraprocessed-food intake to a higher risk of all-cause mortality. The research, which has yet to be published, also found a link to death caused by either heart disease or diabetes.

Related: How long does it take to digest food?

Ultraprocessed meats and soft drinks were the products most strongly associated with mortality risk, Loftfield told Live Science in an email.

Importantly, though, "there are a wide range of foods and beverages classified as ultraprocessed foods according to the NOVA system, and it is unclear how each of these foods impacts human health," Loftfield noted.

Brown added that, although these classifications can be helpful, it may sometimes be tricky to tell if a food is ultraprocessed. Food labels, such as those that say "all natural," can be deceptive and are not regulated by the Food and Drug Administration.

If you're interested in getting professional help to better navigate food choices, a dietitian or nutritionist may be able to guide you toward the healthiest choices for you.

This article is for informational purposes only and is not meant to offer medical advice.

Ever wonder why some people build muscle more easily than others or why freckles come out in the sun? Send us your questions about how the human body works to community@livescience.com with the subject line "Health Desk Q," and you may see your question answered on the website!

Smartwatches and "smart rings" are being marketed as being able to measure blood sugar without requiring a finger prick, but these devices are not authorized by the Food and Drug Administration (FDA) and should not be used, federal officials have warned.

People with diabetes must carefully monitor how their blood glucose levels fluctuate in response to medications, diet and exercise. Inaccurate measurements can lead people to take the wrong dose of insulin or other blood-sugar-lowering drugs, potentially leading to dangerous consequences, like seizures and coma.

Some smartwatch apps report blood sugar levels, but these apps are linked to FDA-authorized devices that do pierce the person's skin, such as continuous glucose monitors. Consumers should be wary of smartwatches that are marketed as monitoring blood sugar all on their own, the FDA cautioned in a statement released Feb. 21.

 Related: What is normal blood sugar?

"The FDA has not authorized, cleared, or approved any smartwatch or smart ring that is intended to measure or estimate blood glucose values on its own," the statement reads. "Be aware that the safety and effectiveness of these devices have not been reviewed by FDA, and the use of these devices could result in inaccurate measurements of blood glucose levels."

The FDA's warning applies to any smartwatch or smart ring that claims to measure blood sugar without piercing the skin. The agency's warning didn't list any specific products but noted that such devices are made by dozens of companies and are sold under multiple brand names. They're often sold through online marketplaces or directly from their makers, the agency noted.

Related: Best fitness trackers 2024

The FDA is now working to ensure that manufacturers, distributors and sellers don't illegally market these devices. In the meantime, the agency urges patients to discuss authorized blood sugar monitors with their medical providers.

"If your medical care depends on accurate blood glucose measurements, talk to your health care provider about an appropriate FDA-authorized device for your needs," officials said in the statement.

Anyone who experiences a problem with inaccurate blood glucose measurement or who experiences any adverse events from using an unauthorized smartwatch or smart ring can report the problem through the FDA's MedWatch Voluntary Reporting Form.

This article is for informational purposes only and is not meant to offer medical advice.

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Humans are not the only mammals that love sugar. Fruit bats do, too, eating up to twice their body weight in sugary fruit a day. However, unlike humans, fruit bats thrive on a sugar-rich diet. They can lower their blood sugar faster than bats that rely on insects as their main food source.

We are a team of biologists and bioengineers. Determining how fruit bats evolved to specialize on a high-sugar diet sent us on a quest to approach diabetes therapy from an unusual angle — one that sent us all the way to Lamanai, Belize, for the Belize Bat-a-thon, an annual gathering where researchers collect and study bats.  Diabetes, the ninth leading cause of death in 2019, can emerge when the body is unable to process sugar effectively, leading to excess glucose in the blood. 

In our newly published research in Nature Communications, we and colleagues Seungbyn Baek and Martin Hemberg used a technology that analyzes the DNA of individual cells to compare the unique metabolic instructions encoded in the genome of the Jamaican fruit bat, Artibeus jamaicensis, with those in the genome of the insect-eating big brown bat, Eptesicus fuscus.

Approximately 2% of DNA is composed of genes, which are segments of DNA that contain the instructions cells use to create certain traits, such as a longer tongue in fruit bats. The other 98% are segments of DNA that regulate genes and determine the presence and absence of the traits they encode.

To understand how fruit bats evolved to consume so much sugar, we wanted to identify the genetic and cellular differences between bats that eat fruit and bats that eat insects. Specifically, we looked at the genes, regulatory DNA and cell types in two significant organs involved in metabolic disease: the pancreas and the kidney.

The pancreas regulates blood sugar and appetite by secreting hormones like insulin, which lowers your blood sugar, and glucagon, which raises your blood sugar. We found Jamaican fruit bats have more insulin-producing and glucagon-producing cells than big brown bats, along with regulatory DNA that primes fruit bat pancreatic cells to initiate production of insulin and glucagon. Together these two hormones work to keep blood sugar levels balanced even when the fruit bats are eating large amounts of sugar.

The kidney filters metabolic waste from the blood, maintains water and salt balance and regulates blood pressure. Fruit bat kidneys need to be equipped to remove from their bloodstreams the large amounts of water that come from fruit while retaining the low amounts of salt in fruit. We found Jamaican fruit bats have adjusted the compositions of their kidney cells in accordance with their diet, reducing the number of urine-concentrating cells so their urine is more diluted with water compared with big brown bats.

Why it matters

Diabetes is one of the most expensive chronic conditions in the world. The U.S. spent US$412.9 billion in 2022 on direct medical costs and indirect costs related to diabetes.

Most approaches to developing new treatments for diabetes are based on traditional laboratory animals such as mice because they are easy to reproduce and study in a lab. But outside the lab, there exist mammals like fruit bats that have actually evolved to withstand high sugar loads. Figuring out how these mammals deal with high sugar loads can help researchers identify new approaches to treat diabetes.

By applying new cell characterization technologies on these nonmodel organisms, or organisms researchers don't usually use for research in the lab, we and a growing body of researchers show that nature could be leveraged to develop novel treatment approaches for disease.

What still isn't known

While our study revealed many potential therapeutic targets for diabetes, more research needs to be done to demonstrate whether our fruit bat DNA sequences can help understand, manage or cure diabetes in humans.

Some of our fruit bat findings may be unrelated to metabolism or are specific only to Jamaican fruit bats. There are close to 200 species of fruit bats. Studying more bats will help researchers clarify which fruit bat DNA sequences are relevant for diabetes treatment.

Our study also focused only on bat pancreases and kidneys. Analyzing other organs involved in metabolism, such as the liver and small intestine, will help researchers more comprehensively understand fruit bat metabolism and design appropriate treatments.

What's next

Our team is now testing the regulatory DNA sequences that allow fruit bats to eat so much sugar and checking whether we can use them to better regulate how people respond to glucose.

We are doing this by swapping the regulatory DNA sequences in mice with those of fruit bats and testing their effects on how well these mice manage their glucose levels.

This edited article is republished from The Conversation under a Creative Commons license. Read the original article.

Migrations of ancient humans in Eurasia may have impacted modern Europeans' risk of developing a variety of diseases, such as multiple sclerosis (MS), type 2 diabetes and Alzheimer's disease.

That's according to two new papers published Wednesday (Jan. 10) in the journal Nature. Along with two other articles from the same researchers, the papers include analyses of DNA from the bones and teeth of hundreds of ancient individuals, the oldest of whom date to the Mesolithic period, or Middle Stone Age. The scientists compared these people's DNA to the genomes of present-day Europeans. 

The project sheds light on the genetic legacy of three ancient human migrations into different regions of Europe: the arrival of hunter-gatherers around 45,000 years ago; Neolithic farmers from the Middle East approximately 11,000 years ago; and sheep and cattle farmers from the Pontic Steppe, a region that spans Eastern Europe and central Asia, around 5,000 years ago. 

In all, the researchers compared the genomes of 1,750 ancient people with those of around 410,000 people who contributed data to a large repository called the U.K. Biobank. All the modern individuals self-identified as British and white, and the authors estimated how much ancient DNA was passed on to them.

Related: Largest-ever genetic family tree reconstructed for Neolithic people in France using ancient DNA

One of the new papers identified gene variants linked to the autoimmune disease MS that were carried by the Pontic Steppe farmers as they migrated mainly into northern Europe; this may help explain why the disease is most prevalent in people of Northern European descent. The researchers concluded these risk variants were "positively selected," meaning they offered some benefit to the migrants and were thus under evolutionary pressure to emerge. 

Specific gene variants related to immune function are known to raise people's susceptibility to MS. These include HLA gene variants, which help the body spot pathogens. However, like a double-edged sword, certain HLA variants are also strongly associated with autoimmune diseases, where the body attacks its own cells.

In the past, these variants potentially helped ancient farmers combat infectious diseases from their animals, the study authors theorize. However, as people's lifestyles changed over time, in terms of their hygiene, diets and medicine, the variants took on new meaning. 

Understanding the evolutionary forces that drove these genes' selection could have implications for treating MS, the study authors hypothesize. Thinking about the double-edged sword, "what we need to move towards is to try to recalibrate the immune response," rather than completely eliminating it, Dr. Lars Fugger, co-senior study author and a professor of neuroimmunology at the University of Oxford in the U.K., said during a press conference on Jan. 9.

In another paper, the authors traced the inheritance of genetic risk variants for 35 complex traits, meaning those caused by a combination of many genes and their interactions with the environment. They discovered that genes associated with lactose tolerance in adults emerged in Europe around 6,000 years ago, and that Northern Europeans today may tend to be taller than Southern Europeans partly due to inheriting genes from the Pontic Steppe farmers. 

They also found that people who carry more DNA from the hunter-gather group they studied may have a greater genetic risk of developing type 2 diabetes and Alzheimer's disease than people who carry fewer of those gene variants. Modern populations with this hunter-gather DNA largely live in Eastern Europe. 

Related: 25,000-year-old human DNA discovered on Paleolithic pendant from Siberian cave

Alzheimer's risk variants may have been positively selected — for example, one risk variant called ApoE4 increases the risk of developing Alzheimer's but may boost fertility in women. 

The fertility boost may have given our ancestors a "huge advantage," Dr. Astrid Iversen, co-senior study author and professor of virology and immunology at the University of Oxford, said during the conference.

"These articles add to the growing stack of evidence that dietary and lifestyle shifts, often accompanying migrations, may have favored alleles that have been maintained within the context of evolutionary trade-offs," Omer Gokcumen, a professor of evolutionary anthropology at the University at Buffalo in New York who was not involved in the research, told Live Science in an email. 

These two studies looked for correlations between specific gene variants and the incidence of different diseases. Because of this, they can't prove that inheriting these ancient gene variants definitively causes these diseases in Europeans today.

"What these papers are doing is they're setting the framework of how you can use these ancient human genomes to understand the origins and spread of disease risk," Eske Willerslev, the director of the project and an evolutionary geneticist at the University of Cambridge and the University of Copenhagen, said during the press conference. 

Editor's note: This article was updated on Jan. 15, 2024 with an updated quote from Omer Gokcumen. The story was first published on Jan. 10, 2024.

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A drug commonly used to treat the autoimmune disease  rheumatoid arthritis (RA) could also slow the progression of type 1 diabetes, an early clinical trial suggests. 

Similar to RA, type 1 diabetes is an autoimmune condition — in RA, the body's immune cells attack the joints, while in diabetes, they destroy insulin-producing beta cells in the pancreas. The resulting insulin deficiency means cells can't remove glucose from the bloodstream, causing blood sugar to skyrocket. Treating type 1 diabetes requires daily insulin injections. 

Now, a clinical trial has shown that a tablet prescribed for RA, called baricitinib, may reduce type 1 diabetes patients' dependence on external insulin. The mid-stage trial, published Dec. 7 in the New England Journal of Medicine, found that baricitinib slowed the progression of diabetes in newly diagnosed patients by preserving their body's ability to make insulin.

The motivation behind the research was "to prevent the loss of insulin secretion rather than managing the absence of naturally produced insulin," Helen Thomas, the preclinical lead on the trial and head of the Immunology and Diabetes Unit at Australia's St Vincent's Institute of Medical Research, told Live Science in an email.

Related: 1st ever drug to delay type 1 diabetes approved by FDA

The team enrolled 91 patients ages 10 to 30 who had been diagnosed with type 1 diabetes less than 100 days before the trial began. (At this point after diagnosis, people's bodies still make some insulin.) Of these, 60 patients received 4 milligrams of baricitinib once a day, while the remaining 31 took a placebo pill. Both groups were treated for 11 months.

Throughout the treatment period, the researchers observed no unwanted side events tied to baricitinib, which suggests the drug is safe for people with diabetes.

After the treatment period, the patients underwent a blood test. Baricitinib-treated patients had higher levels of C-peptide, an indicator of insulin levels, than placebo-treated patients. The pancreas makes C-peptide as it makes insulin, so higher C-peptide level signifies better beta cell function in the baricitinib group.

Indeed, by the end of the study, three baricitinib-treated patients didn't need any external insulin, while others in the group were able to decrease their doses, requiring lesser amounts over time. Meanwhile, the untreated group saw their injected insulin needs slowly increase.

The authors hypothesize that starting patients on baricitinib earlier — immediately after diagnosis or in pre-symptomatic patients identified by screening — may be even more effective.

Through the blood test, they also tested for glycated hemoglobin (HbA1c), which indicates a person's average blood sugar level over the past three months. The HbA1c levels of both groups of patients were comparable, despite the treated group making more insulin.

Thomas attributed this result to the study's design. The researchers had all the participants aim for a target HbA1c value: if their body made more insulin, they would inject less insulin to reach that average blood sugar, while if they made less, they had to inject more insulin to reach that target.

These results didn't surprise the team, because they aligned with observations from previous research conducted on diabetic animals, Thomas said.

Autoimmune reactions involve an enzyme family known as Janus kinases (JAK), whose activity baricitinib inhibits. Previous work from the research group showed that JAK inhibitors disrupt the interaction between immune cells and beta cells, preventing beta cell death. That's why they hypothesized that this class of drugs could potentially slow the progression of type 1 diabetes.

"The trial confirmed what we had suspected," Thomas told Live Science.

The authors noted the trial's limitations, such as the small number of patients included and the short duration of the trial that prevented them from detecting rare side effects. What's more, unlike a drug approved last year to prevent type 1 diabetes progression, which is given during one time period, baricitinib would likely need to be taken continuously to keep working.

The next step involves discussing the trial's results with the Food and Drug Administration, Thomas said.

"While the drug is already approved for other diseases,it is likely that a further trial will be needed before it is approved for type 1 diabetes," she said.

When Ötzi the Iceman was ambushed and killed about 5,300 years ago in the Alps, he may have been balding and getting fat, a new study suggests. 

Ötzi has been famous ever since German tourists discovered his mummified body in 1991 in an Alpine pass in northern Italy. The latest study is one of many to investigate the prehistoric man, including the tools and weapons he carried, his clothes, his last meal, what the climate was like during his lifetime, and the route of his final journey before his high-altitude murder.

In the new study, researchers studied DNA preserved in Ötzi's left ilium — part of his pelvis, which also underwent a genetic analysis in 2012 — and determined that Ötzi, who died in his mid-40s, had a predisposition to male-pattern baldness, diabetes and obesity.

The findings also reveal that Ötzi largely descended from the latest wave of immigrants to Europe from Anatolia — modern Turkey — who brought early farming techniques to the continent about 8,000 years ago. 

The DNA analysis also indicates that Ötzi had darker skin than previously thought and would have had dark hair — before he started going bald, at least.

Related: Ötzi the Iceman had just sharpened his tools days before his murder

Iceman genome

The new study, published Wednesday (Aug. 16) in the journal Cell Genomics, is a revision of the 2012 study by a different group of scientists; genetic tests were complex and costly at that time, and the latest researchers have determined that the earlier samples were significantly contaminated with modern DNA.

The team sampled the same iliac bone, but they used updated genetic techniques to generate a more thorough sequence of Ötzi's genome. They then applied what has been learned about genetics over the past 10 years.

The results show that Ötzi probably looked different than many people thought.

"Ötzi might have had relatively dark skin and a risk of male-pattern baldness," study lead author Ke Wang, an archaeogeneticist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, told Live Science.

The findings are contrary to previous assumptions about Ötzi's appearance; he is often portrayed as looking like a light-skinned European with long fair hair. But "the new findings fit better with the actual appearance of the mummy," Wang said in an email.

Study co-author Albert Zink, a palaeoanthropologist and the director of Italy's Institute for Mummy Studies, noted some of the portrayals should be updated. "It's not urgent, because these are always just an interpretation," he told Live Science. "But in the future they should consider making his skin and hair darker."

Ötzi's genetics also reveal surprising details about his ancestry. Earlier research suggested he may have been related to modern Sardinians, but the new analysis shows he had an unusually high level of ancestry from early Anatolian farmers.

These results suggest that Ötzi came from an isolated Alpine population that seldom interbred with other hunter-gatherer groups, Zink said.

Ötzi reconsidered

The latest study is not the first to reassess who Ötzi was and how he died; an archaeological study last year determined that he probably died somewhere away from the gully where he was found and that his body had been carried there by the subsequent movements of the ice.

Lars Pilø, an archaeologist with the Secrets of the Ice project who led that research but was not involved in the latest study, told Live Science that the latest study resolved the lingering question about whether the skin of Ötzi's mummy was his natural hue. (It was.)

However, Pilø didn't completely agree about Ötzi's baldness. Although Ötzi may have been genetically predisposed to going bald, the hairlessness of his mummy was probably the result of the preservation process, he said.

"Ötzi the Iceman keeps having new surprises in store for us, which is remarkable as he must be the most investigated archaeological find ever," Pilø said.

Over the past year, there has been an explosion in the popularity of GLP-1 receptor agonist drugs — namely Ozempic and Wegovy, which are respectively used to treat diabetes and obesity.   

However, recent reports, heralded by a CNN story published on July 25, have highlighted several cases of persistent vomiting and "stomach paralysis" in people who take the drugs. The U.S. Food and Drug Administration (FDA) also told CNN that they'd received reports of people experiencing such symptoms after taking semaglutide — the active ingredient in Ozempic and Wegovy — but have not yet determined whether the problems arose from the drug itself or from underlying medical issues. 

And in the first case of its kind, a woman in Louisiana has now sued the makers of Ozempic and another GLP-1 agonist, Mounjaro, over claims that the drugs caused her severe gastrointestinal injuries. 

So should consumers be worried? And if so, how might these drugs be causing these side effects? 

Related: Could Ozempic be used to treat addiction? Studies hint yes, but questions remain

How do GLP-1 agonists work?

To make sense of these anecdotal reports, let's go back to the basics of how these drugs work. GLP-1 receptor agonists mimic the action of a hormone — glucagon-like peptide 1 — that the gut secretes after eating. 

GLP-1 has two major roles, Dr. David Levinthal, director of the University of Pittsburgh Medical Center Neurogastroenterology & Motility Center, told Live Science. "One is glucose control, so promoting insulin release and helping reduce blood sugar, and the other is actually programming some of the body's response to a meal, which includes both what the stomach does and what the intestine may do as well."

In the stomach, GLP-1 works almost like a "brake system," essentially slowing down the rate at which the stomach would normally empty food into the small intestine, he said. 

Could GLP-1 agonists cause "stomach paralysis"?

According to Levinthal, stomach problems are a known and common side effect of GLP-1 receptor agonists like Ozempic and Wegovy. Most commonly, these stomach issues include nausea and diarrhea. 

"Probably a lot of the weight loss [caused by these drugs] is because it actually does impact the stomach's function in a way that probably influences people's appetite, because the stomach isn't emptying very well," Levinthal said. Plus, they interact with parts of the brain that regulate appetite.  

Dr. Robert Kushner, a professor of medicine in endocrinology at Northwestern University Feinburg School of Medicine, told Live Science that the way these drugs slow down stomach emptying has been known from "the very beginning of time when these hormones were identified." He explained that patients can expect to experience reduced stomach emptying as their treatment dose is raised to the optimum level, at which point it is crucial that they eat slowly, monitor fat intake and spread meals throughout the day. 

Some users may be more likely to experience a greater reduction in stomach emptying as they are already predisposed to this side effect. For example, if they have type 1 diabetes, where high amounts of blood sugar can cause damage to the vagus nerve that normally instructs the stomach to empty food, Kushner said. Patients with type 2 diabetes may also experience similar symptoms, but their risk is lower than that of those with type 1. In a late-stage trial of Ozempic, which included people with type 2 diabetes, most patients who reported gastrointestinal side effects had mild to moderate symptoms which reduced over time. 

Typically, patients with severely reduced stomach emptying experience symptoms of vomiting, abdominal pain and feeling full after eating only a small amount of food. Kushner warned, however, that referring to this slow stomach emptying as "paralysis" may cause alarm. 

"The medical term [for this condition] is actually gastroparesis, which means slowing of the stomach," he said. The condition is also called gastric stasis, where "statis" refers to a state of inactivity. "Paralysis sounds scary to me, so I can understand why some people would be worried about that." 

"In the vast majority of people, this [drug-induced gastroparesis] is readily reversible with decreasing dose or stopping the medication," Dr. Siddharth Singh, a gastroenterologist at UC San Diego Health, told Live Science in an email.

Related: Watch out for Ozempic copycats containing unauthorized active ingredients, FDA warns

What about "cyclic vomiting"?

According to the CNN report, one Ozempic user who'd experienced gastroparesis was also diagnosed with "cyclic vomiting syndrome" (CVS), and reported having to "throw up multiple times a day" even after she stopped taking the drug.

"Cyclic vomiting syndrome is a distinct disorder that looks a lot different than gastroparesis," Levinthal said. "It's an episodic disorder where people are fine almost all the time, and then have an episode of intense nausea and repetitive vomiting." By comparison, the vomiting associated with gastroparesis tends to occur towards the end of meals or just after someone has finished eating a meal. 

He emphasized that he'd need to know more about the woman to make a diagnosis but implied the need to be cautious in distinguishing between the two disorders and determining the influence of GLP-1 receptor agonists in both contexts. "It would be very unusual, I think, to link these drugs to that disorder [CVS]," he concluded. 

Singh also urged caution about interpreting the reports of vomiting and about being aware of the distinction between typical gastroparesis and CVS. 

"There have been rare reports of this [drug-induced gastroparesis] persisting after stopping the medication," he said. "I would not equate this with 'cyclic vomiting' — cyclic by nature implies intermittent or periodic, and I'm not sure if this drug would cause cyclic vomiting."

Related: Woman who spontaneously vomited up to 30 times a day likely had rogue antibodies

So, what should consumers know?

First and foremost, Kushner warned that when starting one of these drugs, patients should ensure that they're under a clinician's supervision. 

"It is important that anyone who goes on these medications works closely with the prescriber," he said. People should not attempt to take the drugs by other means, for instance, through being "prescribed by the internet without any guidance or supervision."

Patients should also know the potential side effects, and understand what measures can be taken to mitigate them. This may include reducing dietary fat, not skipping meals and staying hydrated, Kushner said. He added that anyone who experiences any side effects should let their prescriber know as soon as possible.

Levinthal also felt that the fear of potential side effects should not put people off taking the drugs if they could benefit from them. 

"It's becoming kind of a cornerstone of treatment for people with gastrointestinal problems — diabetes, and obviously more recently, weight loss, with astounding effect sizes," Levinthal said. "I wouldn't want people to be scared off from even trying the medication in the first place."

The gene activity of "designer" human cells can be remotely toggled on and off with electric currents, a new study in mice shows. 

In a study published July 31 in the journal Nature Metabolism, direct current (DC) from off-the-shelf consumer batteries triggered the release of insulin from genetically engineered human cells that scientists had implanted under the skin of diabetic mice. The insulin successfully restored the rodents' normal blood sugar levels. 

The researchers hope this electrical fine-tuning of gene expression, broadly known as "electrogenetic" technology, will eventually be integrated into wearable devices that can be used to tune the activity of designer cells implanted in the human body. 

Wearable devices are already in vogue and can monitor pulse, blood pressure, blood sugar levels and more. But currently, no such tech can be used to control gene expression.

Related: How fitness trackers monitor your sleep 

To move this idea from science fiction into the real world, Martin Fussenegger, a professor of biotechnology and bioengineering at ETH Zurich and the University of Basel, and his colleagues designed an interface called DC-actuated regulation technology (DART). It's powered by DC from standard 1.5-volt AA or AAA batteries. 

As a proof of concept, they tested DART in a mouse model of type 1 diabetes. They implanted engineered human cells in the rodents' backs and stimulated the cells through two acupuncture needles placed near the implantation site. The needles were attached to the batteries via a wire, whose end was plugged into a simple power switch. 

The electrical current flowed through the needles and triggered minor oxidative stress in the designer cells, meaning it caused a slight buildup of reactive molecules called reactive oxygen species (ROS). These molecules were detected by a molecular sensor built into the cells. 

The sensor, which was engineered to work as a transcription factor — a protein that latches onto DNA to turn a gene "on" or "off" — then bound to a designated spot on the cell's DNA and, in turn, activated the gene of interest, the insulin gene. The human cells were genetically engineered to express, or activate the gene of interest only if the ROS levels produced by the electrical current were high enough, and as the ROS dissipate, the gene switches "off."

Stimulating the designer cells for just 10 seconds once a day was enough to induce gene expression and trigger sufficient insulin release to restore normal blood glucose levels in the lab mice.

Fussenegger told Live Science he thinks this new electrogenetic interface is "a complete game changer."

"It's a tremendous application of electrogenetics," a technique that uses "electronic means to turn on specific gene expression," William Bentley, a synthetic biologist and professor at the University of Maryland who wasn't involved in the research, told Live Science. 

The Fussenegger lab previously designed an electrogenetic device that used alternating current (AC) at high voltage to activate cells, but it required too much power to be suitable for wearables. The new study shows that electronic control of gene expression doesn't need a lot of power or fancy devices, Bentley said. "That’s a significant advance."

Bentley, who pioneered this technology and coined the term "electrogenetics," added that the work still only "represents the tip of the iceberg in terms of electronic communication with and control of biology." Bentley's team first demonstrated electronic control of gene expression in experiments involving engineered bacterial cells, but this new study is the first to remotely regulate gene expression in a mammal using a DC-powered device.

Fussenegger believes that, someday, this technology will not only be integrated into wearables but also link people's metabolisms to "an 'internet of the body.'" This would mean that doctors could intervene remotely, from anywhere in the world, he said. However, devices could eventually be programmed to sense and adjust blood sugar automatically, so "there's nothing for humans to do anymore,” Fussenegger added.

Integrating this technology into smartwatches might not be simple, though, Bentley cautioned. One limitation is that you still need the engineered cells implanted underneath that wristband, which may turn off some people, he said.

Fussenegger conceded that there's still a long way to go. The next steps would entail testing this electrogenetic interface in human clinical trials before it could be commercialized and integrated into wearables.

Some compounding pharmacies are making copycat versions of the diabetes drug Ozempic and the weight-loss drug Wegovy, and people are reporting unwanted side effects from these unauthorized medications, the Food and Drug Administration (FDA) warned this week. 

Compounding pharmacies are those that combine or alter drugs to suit specific patients' needs, by adjusting the dosage or omitting inactive ingredients a person is allergic to, for example; such pharmacies sometimes also make "compounded" versions of commercially available drugs in times of shortage.  

The active ingredient in both Ozempic and Wegovy is semaglutide, which mimics a hormone that's naturally released in the gastrointestinal tract after a person eats. This hormone — glucagon-like peptide-1 (GLP-1) — triggers insulin release, which lowers blood sugar levels by helping usher sugar into cells. Semaglutide also slows the rate at which the stomach empties after a person eats, and it interacts with parts of the brain that help users feel full for longer.

Although it's recently become famous as a celebrity weight-loss drug, Ozempic is approved for lowering blood sugar levels in adults with type 2 diabetes. Wegovy is approved as a weight-loss drug for people ages 12 and up with obesity and for some adults who are categorized as overweight but not obese. The drugs are available with a prescription, and there are no approved generic versions, the FDA notes.

So why are pharmacies making unauthorized versions of Ozempic and Wegovy? Both medications are currently listed on the FDA's drug shortages list, and again, when drugs are in shortage, compounding pharmacies are sometimes permitted to make their own versions by combining ingredients, provided they meet certain federal requirements.  

Related: Diabetes vaccine shows promise for some patients in early trial 

However, compounded drugs are not FDA-approved, and the FDA does not verify their safety and effectiveness as it does for normal drugs. And now, the FDA has received "adverse event reports" from patients who took compounded semaglutide. (The FDA statement doesn't note what kinds of adverse events have been reported.)

"FDA has received reports that in some cases, compounders may be using salt forms of semaglutide, including semaglutide sodium and semaglutide acetate," the agency said in its statement. "The salt forms are different active ingredients than is used [in] the approved drugs, which contain the base form of semaglutide." 

The salt forms of semaglutide likely behave differently in the body and have not been shown to be safe and effective, the FDA stated. The agency is "not aware of any basis for compounding using the salt forms" that would meet the federal requirements for making compounded drugs.

The state pharmacy boards in Louisiana, Mississippi, North Carolina and West Virginia have already sounded the alarm about products containing compounded semaglutide and have told pharmacies to stop making them, NBC News reported in early May. 

Part of the issue is that the approved form of semaglutide can be acquired only from Novo Nordisk, the patent holder for Ozempic and Wegovy, and the company doesn't share drug ingredients with compounding pharmacists, Susan McCoy, executive director of the Mississippi Board of Pharmacy, told NBC News. Novo Nordisk recently lined up a second manufacturer to up the Wegovy supply in face of growing demand, but it's still facing some manufacturing delays, Fierce Pharma reported.

The FDA advises consumers to obtain semaglutide-based drugs only if they have a prescription from a licensed medical provider and to only get the drugs from state-licensed pharmacies or FDA-registered outsourcing facilities. 

"If you choose to use an online pharmacy, FDA's BeSafeRx campaign resources and tools can assist in making safer, more informed decisions when purchasing prescription medicine online," the agency said. 

For someone prone to migraines, a missed meal could be a fast-track to an attack. Out-of-balance blood sugar is a well-established trigger for migraines and other types of headaches. Now, a new study adds genetic evidence to back up the connection and could potentially inform future strategies for treating migraines.

By analyzing genomic data from tens of thousands of people, researchers have identified genetic links between migraines and problems with blood sugar regulation. Their findings hint at a shared genetic basis for the conditions, and also point to new migraine-related genes for further study, the team reports in a paper published Feb. 20 in the journal Human Genetics.

Migraines affect almost 15% of people worldwide and are three times more common in women than in men, according to the World Health Organization. They can be set off by many different triggers, such as hormonal fluctuations, lack of sleep and even certain foods. But researchers still don't fully understand why some people are prone to frequent migraines. Some scientists are sifting through the genome for clues, hunting for genetic risk factors and links to other medical conditions.

"Discovering concrete links to other potential facets of the disease — in this case blood sugar regulation — can help to further advance our understanding of migraine," said Dr. Leon Moskatel, a headache specialist at Stanford University School of Medicine who wasn't involved in the work. The work raises questions about whether future treatments for migraine could work by somehow targeting blood sugar, he told Live Science in an email. 

Related: What is normal blood sugar? 

The analysis includes genetic data from more than 100,000 migraine patients and 84,000 patients with headaches, more generally, compiled from several previous studies. It also pulls in data on genome regions that have previously been related to different aspects of blood sugar regulation; these included genes linked to people's average blood sugar levels, their blood sugar and insulin levels after fasting, and their rates of type 1 diabetes.

By comparing those datasets, the team identified regions of the genome that appear to affect both blood sugar regulation and migraine risk.

One blood sugar measure that stood out was fasting proinsulin, which was actually linked to a reduced risk of migraine, said study coauthor Rafiqul Islam, a graduate student in the lab of Dale Nyholt at Queensland University of Technology in Australia. Proinsulin is the chemical precursor to insulin, a hormone that lowers blood sugar levels; "fasting proinsulin" refers to the amount of proinsulin in the blood after a period without food. 

Having higher levels of fasting proinsulin is associated with insulin resistance in type 2 diabetes, one study found, and it may reflect dysfunction in the cells responsible for making insulin in the body, another found. But higher levels of fasting proinsulin might also protect against migraines and other headaches, Islam's genetic analysis suggested. The finding seems to align with some previous studies suggesting people with type 2 diabetes have a reduced risk of migraine attacks, but much more research is needed to confirm this link.  

The team also identified a number of gene variants that hadn't previously been associated with migraines or blood sugar, so their relationship to the disorders remain unclear. Learning more about these genes is a target for future research, Islam told Live Science. "If we can identify the function of these genes, we could develop new strategies for treatment," he said.

Future research could add more nuance by looking at people from non-European backgrounds, since the current study exclusively included people of European descent, Moskatel suggested. Plus, migraines come in different types — both with and without "aura" — and there could be different underlying processes driving them. (An aura describes neurological symptoms that arise before and sometimes during a migraine, such as visual hallucinations or physical sensations like numbness.)

"Having that differentiation in future studies could be illuminating," he said.

A young woman experienced spontaneous vomiting attacks during which she would sometimes retch more than 30 times a day and heave up to 1.6 gallons (6 liters) over the full course of an episode. It turns out, the symptoms likely stem from an underlying autoimmune disorder. 

According to a report of the case, published Nov. 10 in the journal Frontiers in Endocrinology, the 27-year-old woman also has type 1 diabetes, an autoimmune disease in which the immune system attacks cells in the pancreas that produce the hormone insulin. Insulin helps shepherd sugar out of the bloodstream and into cells, but the disease reduces the body's supply of the hormone, which causes blood sugar, or glucose, levels to rise. 

About 1 in 5 people with type 1 diabetes have an additional autoimmune disorder of some kind, according to a 2020 report in the journal Diabetes Care. In the woman's case, such an autoimmune disorder seems to drive her vomiting episodes, although her doctors are still working out how.

The doctors first examined the patient in 2016, when she began experiencing vomiting episodes about once a month. Before each, the patient felt an "impending sense of doom and came to our hospital for help in a state of panic," the authors wrote. The patient would then develop nausea, excruciating abdominal pain and vomiting. "The episodes were so severe that the patient had vomiting episodes more than 30 times a day and the vomiting volume could be as large as 6 liters [1.6 gallons]."

Related: 27 oddest medical case reports 

Based on the pattern of the patient's episodes, the team diagnosed her with "cyclic vomiting syndrome" (CVS), a disorder characterized by sudden vomiting attacks interspersed with long periods without symptoms. The exact cause of CVS is unknown, but researchers think it might arise from errant nerve signals between the brain and digestive tract; dysfunctional hormonal responses to stress; or certain genetic mutations, according to the National Institute of Diabetes and Digestive and Kidney Diseases.

After hospital admission, the patient's symptoms usually subsided over several days, but her blood sugar would then plummet and stay low for days, despite her insulin treatment being tightly controlled.

To unpack this complex case, the medical team conducted a whole-body exam, "but nothing significant was found," case report author Dr. Wei Liang, a physician in the endocrinology department at University of Hong Kong-Shenzhen Hospital, told Live Science in an email. However, an analysis of the patient's blood revealed "extremely high" levels of GAD autoantibodies, which are immune molecules that inadvertently attack the body's own tissues and are found in patients with type 1 diabetes, she said. 

The patient's blood also contained antibodies that latch onto insulin, which can sometimes develop in people who need insulin injections. Oddly, the team found that the antibodies seemed to make the insulin hang around for longer than is typical for people who take insulin. 

"We observed an unusual phenomenon of 'insulin recycling' in this patient," where the hormone was reentering the bloodstream rather than being efficiently broken down by cells, case report author Aimin Xu, a professor in the University of Hong Kong's State Key Laboratory of Pharmaceutical Biotechnology, told Live Science in an email.

There are several theories as to how insulin antibodies might cause this to happen, but the phenomenon isn't well understood. However, the antibodies did explain why the patient's blood sugar was dropping, so her doctors tried depleting the antibodies with different drugs. They found that rituximab, which tags antibody-producing immune cells for destruction, reduced the number of antibodies and corrected the low blood sugar.

Unexpectedly, "vomiting symptoms were remarkably reduced in our patient in the eight-month follow-up after one course of rituximab treatment," Liang told Live Science. The team suspects that the autoantibodies in the patient's blood were somehow driving her CVS, so when those antibodies disappeared, so too did the patient's vomiting episodes.

"In our opinion, cyclic vomiting syndrome is not likely linked to diabetes or insulin use," because the syndrome isn't more common in diabetic people than it is in the general public, Liang said. "Therefore, we think CVS may be a separate autoimmune disorder," she said. 

To test this hypothesis, the team plans to study the patient's case and autoantibodies further, and eventually, they may consider conducting clinical trials with rituximab as a treatment for CVS, Xu said.

The first drug to delay the onset of type 1 diabetes in those nearly certain to develop the autoimmune disease has been approved by the U.S. Food and Drug Administration (FDA), the federal agency announced Thursday (Nov. 17).

In type 1 diabetes, the immune system progressively wipes out insulin-producing cells, called beta cells. The new treatment, called teplizumab-mzwv (brand name Tzield), is a lab-made protein that behaves like an antibody made by the human immune system. Once in the body, the so-called monoclonal antibody latches onto immune cells called T cells and reprograms them so they don't aggressively attack beta cells in the pancreas, according to a statement from drugmaker ProventionBio. At the same time, it boosts the number of immune cells that counteract such attacks. 

Insulin acts as a key that unlocks cells so that sugar from the bloodstream can enter them. When the body doesn't make enough insulin, blood sugar levels skyrocket. 

Before a person develops full-blown type 1 diabetes, they progress through several preliminary stages of disease, according to Emory University School of Medicine. In stage 1, beta cell-targeting antibodies begin to appear but blood sugar levels remain normal, and in stage 2, blood sugar levels become a little elevated in some situations, but people still show no diabetes symptoms.

Related: What is normal blood sugar? 

By stage 3, a bulk of the beta cells have been destroyed and people show symptoms, such as extremely elevated blood sugar levels, frequent urination, weight loss and thirst, and they can sometimes develop a life-threatening condition called diabetic ketoacidosis. Most people receive a type 1 diagnosis at this stage. People are most often diagnosed as children or young adults, but type 1 diabetes can develop at any age.    

In a clinical trial, teplizumab-mzwv delayed the transition from stage 2 to stage 3 for a little more than two years, compared with a placebo treatment, according to the FDA. Two years was the median time until diagnosis, meaning some participants transitioned to stage 3 sooner and some did so later. 

The antibody is now approved for use in people ages 8 and older with stage 2 type 1 diabetes.

"The drug's potential to delay clinical diagnosis of type 1 diabetes may provide patients with months to years without the burdens of disease," Dr. John Sharretts, director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA's Center for Drug Evaluation and Research, said in the agency's statement. 

The trial included 76 participants who were between 8 and 49 years old and had stage 2 type 1 diabetes; more than 70% of the participants were younger than age 18, according to ProventionBio. The participants were randomly split into two groups, one of which received daily IV infusions of teplizumab-mzwv for two weeks while the other group received placebo infusions.

The most common side effects of teplizumab-mzwv were rash, headache and a decrease in the numbers of certain immune cells, according to ProventionBio. In most patients who experienced the latter side effect, these immune cell counts began rebounding within a week of them concluding treatment and fully recovered within a few months.

Patients who take teplizumab-mzwv should be monitored for signs of a potentially dangerous reaction called "cytokine release syndrome," in which T cells suddenly unleash a flood of inflammatory molecules into the bloodstream. This occurred in some trial participants, ProventionBio cautioned. 

Patients should also be monitored for signs of serious infection, as their immune protection may be lower than usual during and following treatment, and any "hypersensitivity reactions," such as vomiting or swelling beneath the skin (angioedema). And because teplizumab-mzwv may interfere with immune response to vaccination, all age-appropriate vaccinations should be given prior to the treatment's start.

Teplizumab-mzwv costs $13,850 a vial, which adds up to a total of $193,000 over the 14-day treatment, USA Today reported. 

Sugar may disrupt the community of bacteria living in the gut, thereby depleting crucial immune cells and causing obesity down the line, a new mouse study suggests. 

So far, the results have been shown only in mice. But if follow-up studies show similar trends in humans, that could eventually lead to treatments for metabolic disease and obesity, said senior author Ivaylo Ivanov, an associate professor of microbiology and immunology at Columbia University Vagelos College of Physicians and Surgeons. 

In the recent study, published online Aug. 29 in the journal Cell, scientists found that feeding mice a high-sugar diet containing sucrose and maltodextrin caused specific bacteria, called segmented filamentous bacteria (SFB), in the mice's intestines to die due to an overgrowth of different gut bugs. The sudden loss of SFB triggered a chain reaction in the mouse gut that ultimately changed how the animals absorbed dietary fat. 

This, in turn, caused the mice to become obese and develop features of "metabolic syndrome," a cluster of conditions — such as high blood pressure, high blood sugar and insulin resistance — that collectively raise the risk of heart disease, stroke and type 2 diabetes. 

Related: Gut bacteria may 'talk' to the brain, mouse study suggests 

The results suggest that SFB somehow protect against metabolic syndrome and excess weight gain, but how do the gut bugs do it? It turns out that SFB "talk" to the immune system, encouraging the production of a specific type of immune cell called Th17. These immune cells release proteins that affect the lining of the intestine, preventing excess fat from being absorbed through the tissue and into the bloodstream. 

Broadly, SFB can be found in many animals — including rodents, fish and birds — but they haven't been found in humans, Ivanov noted. However, humans do carry a different set of gut bacteria that can induce Th17 cells just like SFB do, and early research hints that these bacteria may be similarly depleted by high-sugar diets, he said. In other words, although humans may not carry SFB, sugar may still exert similar effects on the mouse and human gut microbiomes and immune systems.

"Really what's providing the effect is the T cells — so the bacteria are inducing the T cells, and T cells are providing the effect," Ivanov told Live Science. "We hypothesize that, in humans, inducing these T cells will also be beneficial."

In their recent mouse study, the researchers placed mice on a high-sugar, high-fat diet for a month to see how their gut bugs might change. They found that the diet spurred the growth of a bacterium called Faecalibaculum rodentium, which essentially crowded out the SFB growing in the mouse gut, depleting its numbers. As the mice steadily lost SFB, their overall number of Th17 cells also fell, and they gained weight and developed insulin resistance and glucose intolerance — all signs of metabolic syndrome. 

These effects weren't observed in mice that were fed a low-sugar, low-fat diet, or in mice fed a sugar-free, high-fat diet, but mice fed a high-sugar, low-fat diet also swiftly lost their SFB. This suggests that it was specifically the sugar that was driving the harmful loss of the bacteria and the Th17 cells. 

Basically, the Th17 cells provided an "armor" that protected the mice from developing metabolic disease, and sugar indirectly destroyed that armor by messing with the microbiome, Ivanov explained.

In a different experiment, the team eliminated SFB from a group of mice and then fed them a sugar-free, high-fat diet. They found that these mice also gained weight and developed metabolic disease, despite not having eaten sugar. So what gives? In essence, without the right gut bugs, the mice didn't make enough Th17 cells and they thus lacked that aforementioned armor. The team found that they could provide that armor in two ways: by feeding the mice a probiotic imbued with SFB or by directly injecting Th17 cells into their bodies.

This suggests that, if a mouse's gut has already been depleted of SFB, cutting down on sugar won't help the rodent avoid metabolic disease. If this finding carries over to humans, that suggests that consuming less sugar wouldn't necessarily be helpful if one's gut microbiome is already disrupted. Therefore, an additional intervention might be needed to restore the gut bugs or Th17 cells of those people, Ivanov said.  

Again, more research is needed to know if similar forces are at work in the human gut. Ivanov and his team are also trying to understand how gut bacteria help Th17 cells grow in the mouse gut and whether that mechanism also applies in humans.

"Even after 10 years of studying this, we don't understand completely this process, this mechanism, how exactly the bacteria is inducing these T cells," Ivanov said. "We know a lot, but still there are a lot of questions."

Originally published on Live Science.

While most of us are familiar with type 1 and type 2 diabetes, you may not have come across the term ‘type 3 diabetes’ before. First things first, this is not to be confused with type 3c diabetes, which is something else entirely. It is, however, related to insulin resistance in the brain. 

Being diagnosed as insulin resistant generally means that someone is either prediabetic or has type 2 diabetes. But scientists have proposed that it can also result in the brain’s neurons lacking glucose, which is needed for proper function, and this can lead to symptoms of Alzheimer's disease. 

While type 3 diabetes is not an officially recognized health condition, in 2008 Dr Suzanne de la Monte and Dr Jack Wands of Brown University put forward a proposal that Alzheimer’s disease could be termed ‘type 3 diabetes’ due to its strong links with insulin resistance in the Journal of Diabetes Science and Technology. Insulin resistance may be a leading cause of dementia, as this glucose metabolism deficiency in the brain contributes to symptoms such as loss of memory, decrease in judgment and reasoning skills.

What is type 3 diabetes?

Type 3 diabetes is not a medically recognised term and is not something doctors use for diagnostic purposes. However, insulin resistance and decreased insulin signaling in the brain may play a role in the development of Alzheimer's disease. Not to mention, the risk of developing Alzheimer's disease is significantly higher in those with type 2 diabetes. As such, the term ‘type 3 diabetes’ has been colloquially used by some in the field to illustrate these links. A study in the Lancet journal of Neurology links diabetes with declining brain health and indicates that treatments that restore cerebral insulin function may offer therapeutic benefits to those with Alzheimer's disease. 

Dr. William H Frey II PhD., an Alzheimer's research specialist at the Health Partners Center for Memory and Aging, also explains that the disease causes cognitive decline in patients. “Alzheimer's is a degenerative brain disease that accounts for more than 60% of the cases of dementia,” he tells Live Science. “It is characterized by memory loss, especially short-term or recent memories, cognitive decline and changes in behavior, all of which get progressively worse over time.” 

Dr Tariq Mahmood, a medical doctor with 30 years experience, and the medical director at Concepto Diagnostics, adds: “Type 3 diabetes isn’t an officially recognized health condition and isn’t used for diagnostic purposes. It differs from type 1 diabetes and type 2 diabetes, which cause blood sugar levels to become too high due to issues with a hormone called insulin. Some scientists hypothesize that insulin dysregulation in the brain causes dementia and use type 3 diabetes as a term to describe Alzheimer’s disease – a progressive neurological condition which is the most common cause of dementia.” 

Type 3 diabetes: Symptoms and diagnosis

Mahmood explains that while ‘type 3 diabetes’ is not an official diagnosis, doctors can diagnose Alzheimer’s disease, which affects multiple brain functions gradually over the course of many years. “Minor memory problems are usually the first sign,” he says. “More specific symptoms can include confusion, difficulty planning, disorientation, getting lost and personality changes.”

Early to moderate symptoms of Alzheimer's include: 

• Lack of judgment
• Memory loss
• Confusion
• Agitation/anxiety
• Problems with reading, writing, numbers
• Difficulty recognising family and friends
• Disorganized thoughts
• Lack of impulse control

These symptoms usually develop to a point that patients cannot swallow, lose bowel control and eventually pass away. Often people with Alzheimer's die from aspiration pneumonia. This develops when problems swallowing cause food or liquids to pass into the lungs instead of air due to problems with swallowing, as is stated by the National Institute of Aging. Dr Frey tells us that Alzheimer’s is best diagnosed by a neurologist familiar with neurodegenerative memory disorders. “Diagnostic procedures may involve taking a complete history, blood tests, brain imaging, neuropsychological testing, etc. to help rule out other disorders that may produce somewhat similar symptoms,” he says.

What causes type 3 diabetes?

A review on insulin resistance in Frontiers in Neuroscience indicates that insulin is involved in multiple common conditions, such as obesity, dementia and diabetes. The review discusses how antidiabetic medications may be used to prevent and/or treat Alzheimer’s dementia, along with addressing stress, life events and other environmental challenges. 

Mahmood tells us that while the science is unclear on the specific cause of Alzeimer’s disease, a combination of factors may be at play. “It’s widely believed that age-related neurological changes combined with genetic, environmental, and lifestyle factors can contribute toward it,” he says. “Age is the most important known risk factor for Alzheimer’s disease due to, among other things, atrophy in parts of the brain. Atrophy is the loss of brain tissue, meaning it can shrink, thin or be outright lost."

Dr Frey explains that general aging is not the only risk factor associated with the development of Alzheimer's disease. “Aging is the major risk factor for Alzheimer's disease, but Alzheimer's is not a normal part of aging,” he says. “A family history of Alzheimer's and genetic changes can also increase the risk, but individuals without a family history of the disease can still get it. A history of moderate traumatic brain injury can also significantly increase the risk for developing Alzheimer's disease. 

“Finally, type 2 diabetes doubles the risk for developing Alzheimer's disease. This is likely due to the fact that in both diabetes and Alzheimer's disease, there is a deficiency of insulin signaling.” 

He goes on to explain that in Alzheimer's disease, the insulin signaling deficiency leads to a loss of brain cell energy. Without sufficient insulin signaling, blood sugar is not taken into brain cells and metabolized normally. 

“Loss of brain cell energy means that the brain can no longer carry out memory and cognitive functions normally and also can not produce the parts of brain cells needed to replace those that wear out over time leading to degeneration of the brain itself.”

Unhealthy lifestyles, including lack of exercise, poor diet and lack of sleep, likely also increase the risk for Alzheimer's disease, he says.

Treatment

TREATMENT

Dr Frey’s research has been pioneering in the area of insulin resistance and Alzheimer's. In 2022, in a study in Pharmaceuticals, Frey and colleagues studied biomarker uptake in brain regions implicated in the faulty uptake and metabolism of blood sugar in Alzheimer’s patients. Studies like these may identify new therapeutic modalities and help explain why emerging therapies, such as intranasal insulin (insulin administered up the nose) are effective in treating Alzheimer’s, Parkinson’s and other neurodegenerative disorders.

“Because insufficient insulin signaling contributes to loss of brain cell energy in individuals with Alzheimer's disease, [I] first proposed intranasal insulin as a treatment for Alzheimer's disease about 22 years ago,” he says. “Intranasal insulin targets and delivers insulin to the brain along the nerves involved in smell without altering the blood levels of insulin or blood sugar.”

Clinical trials have shown that intranasal insulin increases brain cell energy and improves memory in normal healthy adults, as well as those with mild cognitive impairment or Alzheimer's disease. However, it needs further development and testing to sufficiently demonstrate its safety and efficacy before it can be considered for regulatory approval and made available to patients.

Dr Mahmood tells us that while there is regrettably no cure for Alzheimer's disease, treatments for those with the condition are available. “There are medicines and treatments that can reduce symptoms on a temporary basis,” he says. “The two main medicines right now are acetylcholinesterase (AChE) inhibitors, which help nerve cells communicate with each other, and memantine, which blocks the effects of excessive glutamate – this is a neurotransmitter released by nerve cells which plays a major role in learning and memory.” 

For people who begin to show aggression or distress, antipsychotic medicines can also be prescribed. Other treatments, like cognitive rehabilitation and cognitive stimulation therapy, can help maintain memory and problem-solving skills.

Can you prevent type 3 diabetes?

A review in the Journal of Alzheimer's Disease indicates meditation may help prevent Alzheimer’s disease. It reduces allostatic load, which has been linked to the development of several cognitive disorders. The review found that 12 minutes of Kirtan Kriya meditation per day was seen to improve function of insulin and glucose regulatory genes. It was also indicated to improve sleep, decrease depression and anxiety, down-regulate inflammatory genes and  upregulate immune system genes. 

Dr Mahmood recommends general healthy living to reduce your risk too, although other risk factors are uncontrollable. “Unfortunately, there’s no way to prevent Alzheimer’s disease at the moment,” he says. “Living a healthy lifestyle might lessen your risk, but age-related neurological changes and genetic factors are impossible to work around. Cardiovascular disease has been linked with an increased risk of Alzheimer's disease, so eating a balanced diet, making sure you get 150 minutes of exercise per week, limiting alcohol consumption and stopping smoking are all worthwhile.”

Our easy Mediterranean diet plan and 7-day plant-based diet meal plan have lots of ideas to help you to eat a more balanced diet.

Dr Frey agrees that general healthy living is a wise course of action to reduce your risk of  Alzheimer's disease. He also recommends protecting your head. “Maintaining a healthy lifestyle including regular physical activity, avoiding head injury by wearing your seatbelt while in vehicles and a helmet during sports, consuming a healthy diet and remaining socially active can all help to reduce your risk for Alzheimer's disease,” he says.

This article is for informational purposes only and is not meant to offer medical advice.

Diabetes is a chronic disease characterized by high blood sugar, or glucose. 

This glucose, which is derived from the food we eat, is a critical source of energy for the body's cells. Once glucose enters the blood, the pancreas releases the hormone insulin, which shepherds the glucose from the blood into cells, feeding them their essential fuel. 

However, in people with diabetes, the body doesn't make enough insulin or doesn't use the insulin as it should. As a result, their blood sugar remains elevated. Over time, these high blood sugar levels can lead to serious complications, including heart disease, kidney disease and blindness, according to the Mayo Clinic.

Related: What is normal blood sugar?

About 11.3% of the U.S. population, or 37.3 million people, has diabetes, according to a recent report from the Centers for Disease Control and Prevention (CDC); about 8.5 million, or 23%, of those people have undiagnosed diabetes. In addition, about 96 million people in the U.S. have prediabetes, a condition in which blood sugar levels are high but not high enough to be diagnosed as diabetes, but most are unaware of it.

Types of diabetes

There are three broad categories of diabetes, according to the Mayo Clinic: type 1 diabetes, type 2 diabetes and gestational diabetes.

Type 1 diabetes is an autoimmune disease, because the person's own immune system mistakenly attacks the insulin-producing cells (called beta cells) in the pancreas. This stops the secretion of insulin, thus allowing sugar to build up in the bloodstream. 

Type 2 diabetes occurs when the body's cells do not respond to insulin the way they should. At first, the pancreas makes up for the shortfall by secreting more insulin, but eventually, it cannot keep up, causing sugar to build up in the bloodstream.

Gestational diabetes happens when someone who did not previously have diabetes develops diabetes during pregnancy. During pregnancy, the hormones produced to sustain the pregnancy, such as estrogen and cortisol, make the pregnant person's own cells more resistant to insulin, according to Johns Hopkins Medicine. Normally, the pancreas produces more insulin to compensate, but sometimes, it can't keep up, allowing glucose to build up in the bloodstream. Sometimes, gestational diabetes resolves after pregnancy; other times, the condition becomes chronic.

• Related: Which vegetables are good for Diabetics 
• Related: Which fruits are good for diabetics

Prevention & risk factors

Although type 1 and type 2 diabetes have different causes, they share two key risk factors: the person inherits a predisposition to the disease, and then something in their environment triggers it, according to the American Diabetes Association (ADA).

In most cases of type 1 diabetes, people inherit genetic risk factors from both parents — it is believed these factors are more common in white people, because they have the highest rate of this form of diabetes, says the ADA.   

Environmental triggers, according to the ADA, can include cold weather (type 1 diabetes develops is more common in cold climates) and certain viral infections (enteroviruses are considered the strongest candidates), according to the National Library of Medicine. Diet and lifestyle habits don’t cause type 1 diabetes, adds the CDC. 

At the moment, there is no known way to prevent type 1 diabetes, but researchers are working on research to do just that, as well as limit the destruction of insulin producing cells in the pancreas of newly diagnosed patients, according to a 2020 paper published in the journal Frontiers in Endocrinology.

Genetics plays a role in type 2 diabetes, so someone who has a family history of the disease is more likely than others to develop it, according to the National Institutes of Health. Other factors that increase a person's chances of developing this type of diabetes include: being 45 years or older, being overweight or obese, having other health conditions such as high blood pressure, along with other risk factors, the NIH says. A person who is African American, American Indian, Asian American, Pacific Islander or Hispanic American, has an increased risk of developing type 2 diabetes, according to the CDC.

Lifestyle changes can lower a person's risk of developing type 2 diabetes and are especially important for people who have prediabetes, according to the CDC. Data shows that even moderate weight loss and exercise can prevent or delay type 2 diabetes in people at high risk of developing the condition, according to this 2010 paper published in the journal Diabetes Care.

People who had gestational diabetes are also at increased risk of developing type 2 diabetes later in life. High blood pressure and/or abnormal cholesterol and triglyceride levels are other risk factors for type 2 diabetes.

Symptoms & complications

Symptoms of high blood sugar include frequent urination, persistent thirst and hunger, sores that take long to heal, blurry vision, loss of weight without trying and tingling extremities, the CDC says. 

Type 1 diabetes typically starts in childhood or as a young adult, but it can occur at any age. It may also include symptoms such as nausea, heaving or stomach pains. 

Type 2 diabetes typically starts in adulthood, but more and more people are developing it at a young age.  Symptoms of high blood sugar usually emerge slowly, so they aren't always easy to spot. Therefore, it is important to pay attention to factors that raise the risk of diabetes. 

There has been a surge in cases of both type 1 and type 2 diabetes among youth, a recent CDC report says. Between 2001 and 2017, the number of people under age 20 living with type 1 diabetes increased by 45%, and the number living with type 2 diabetes grew by 95%, the agency said. 

Gestational diabetes usually doesn't have any symptoms, but doctors often test for it between the 24th and 28th week of pregnancy.  

If diabetes is left uncontrolled, it can lead to serious — and sometimes life-threatening — complications. The longer the disease is untreated, the higher the risk of these complications, according to the Mayo Clinic.

Diabetes dramatically raises the likelihood of heart disease and other cardiovascular events, including heart attacks and strokes, according to a review of existing research published in 2015 in the World Journal of Diabetes. It all stems back to persistent high sugar levels, which over time can damage the arteries that carry blood, oxygen and nutrients around the body, says the British Heart Foundation. Once the arteries are damaged, it’s easier for fat to clog up arterial walls and limit blood flow. If the arteries carrying blood to the heart are obstructed, it can lead to a heart attack — if the arteries carrying blood to the brain get congested, that can culminate in stroke.

Nerve damage is also a common complication , as excess sugar can impair the walls of the tiny blood vessels that nourish the nerves, eventually leading to a condition called neuropathy, or a loss of all sense of feeling in the affected limbs that affects more than 90% of people living with diabetes, according to a 2015 study published in the World Journal of Diabetes. That nerve trauma may also make people more vulnerable to infections and lead sores and cuts to heal more slowly. In particular, people with diabetes are susceptible to problems in their legs and feet, which can result in amputation if left untreated, says the Mayo Clinic.

Diabetes can also damage the kidneys, which contain millions of blood vessel clusters that filter waste in blood. If left unaddressed, a person with kidney damage resulting from diabetes may need dialysis, or even a kidney transplant. Research suggests that diabetes has become the single most frequent cause of end-stage kidney disease, according to a 2019 paper published in the journal Molecular Metabolism.  Uncontrolled blood sugar can also weaken the blood vessels of the eye (diabetic retinopathy) to the point of causing blindness, says the Mayo Clinic.

A common but severe complication of type 1 diabetes (and, less commonly, type 2 diabetes) is diabetic ketoacidosis, which occurs when there is a drastically low level of insulin in the body, according to the National Library of Medicine. This means the body can't use sugar for energy, so it starts to use fat instead. As a result, compounds called ketones are released, causing the blood to become acidic and, in turn, toxic. Diabetic ketoacidosis is sometimes the first sign of type 1 diabetes in people who haven't been diagnosed; if left untreated, it can be deadly.

Diagnosis

The American Diabetes Association recommends screening for type 2 diabetes for all adults age 45 and older, as well as for: Individuals who are overweight or have obesity, plus have one or more diabetes risk factors; women who have  had gestational diabetes; people with prediabetes; kids who are overweight or have obesity, and have a family history of type 2 diabetes or one or more other risk factors, according to the Mayo Clinic. 

Normal blood sugar levels vary from person to person, but a normal range for fasting blood sugar (the amount of glucose in your blood at least eight hours after a meal) is between 70 and 100 milligrams per deciliter (mg/DL), according to the World Health Organization (WHO). According to the ADA, the normal blood sugar range two hours after someone eats is generally less than 140 mg/DL, according to the ADA.

There are several ways for doctors to diagnose diabetes, according to the ADA (but each test typically needs to be repeated on a second day to diagnose diabetes):

• One method is the A1C blood test, which measures average blood glucose over the preceding three months. The test measures glucose attached to hemoglobin, the oxygen-carrying protein in blood. The red blood cells that carry this protein live for about three months, so measuring them at a single time point provides a snapshot of the general level of glucose in the blood. An A1C result of less than 5.7% is considered normal,  between 5.7% and 6.4% suggests prediabetes, and 6.5% or greater indicates diabetes.
• Another test, the fasting plasma glucose test, reveals how effectively the body metabolizes glucose and requires the patient to fast for eight hours before taking the test. More than 126 mg/DL of glucose in the blood signals diabetes.
• The oral glucose tolerance test, which is often used to detect gestational diabetes, requires the patient to consume a very sugary drink. Two hours later, the person undergoes a blood test. A repeated result of 200 mg/DL or greater of glucose in the blood would mean a diabetes diagnosis.
• Given that a family history of diabetes raises the risk of developing the condition, people who fall into that category should talk to their doctor about being screened.

Treatment

People with diabetes are usually asked to regularly monitor their blood sugar levels in order to keep an eye on the impact of medication, diet and exercise on their glucose levels, says the Mayo Clinic. Keeping track of these levels can be done by either using a device called a continuous glucose monitor (CGM), which measures blood sugar every few minutes using a sensor inserted under the skin, or with the help of a portable electronic device called a blood sugar meter using a small drop of blood.

The treatment for type 1 diabetes is regular insulin injections, sometimes delivered with an insulin pump, a catheter device that automatically dispenses the hormone, alongside attention to diet and exercise to prevent complications. 

The first step in managing type 2 diabetes is to lose weight by eating healthy — including smaller portion sizes; increased intake of high-fiber foods such as fruits, non-starchy vegetables and whole grains; and fewer calories — and getting regular exercise, says the Mayo Clinic. A keto diet could also be a potential for type 2 diabetics.

• Related: Keto diet vs low carb

Doctors also may prescribe insulin, other injectable medications or oral diabetes medicines, such as metformin, to address the high blood sugar. Patients are typically given blood sugar targets and are advised to check their glucose levels periodically.  

ADA guidelines indicate that weight loss surgery, also called bariatric surgery, is an option for individuals with inadequately controlled type 2 diabetes and a BMI of 35 or greater, according to Penn Medicine Lancaster General Health.

In 2016, the FDA approved the use of an "artificial pancreas" that automatically tests blood glucose levels periodically and releases insulin accordingly, Live Science previously reported. The product relies on a coin-size transmitter attached to a tiny needle that is inserted into the skin to continuously track glucose levels, a pump that delivers precise doses of insulin as needed through a separate catheter, and a computer chip that uses data from both components to optimize the delivery of insulin on a minute-by-minute basis.

Is diabetes curable?

Although research is ongoing, type 1 diabetes has no cure, says the Mayo Clinic. For example, researchers have found a way to convert human stem cells into insulin producing cells that at least in mice have shown to control blood sugar levels, according to a 2020 study published in the journal Nature Biotechnology.  

There is no cure for type 2 diabetes either, but with substantial and sustained weight loss, patients can go into remission, which means their blood sugar levels fall into the normal range again, according to the NIH. However, this doesn't mean the person has been "cured" or completely rid of diabetes for good, because blood glucose levels tend to fluctuate with weight, so if the person regains the weight, their blood sugar levels could elevate to a diabetic range back again.   

Some studies have shown that bariatric surgery can help some diabetes patients achieve remission.  For instance, in a UK study involving about 2500 patients with type 2 diabetes, researchers found an 18-fold increased chance of diabetes remission after bariatric surgery in comparison with patients not undergoing surgery, according to a 2015 study published in the journal JAMA Surgery.

Another study, published in the journal The Lancet Diabetes & Endocrinology in 2019, showed that more than a third (36%) of people with type 2 diabetes who took part in a weight management program were in remission two years later.

This article is for informational purposes only and is not meant to offer medical advice.

This article was updated on Apr. 14, 2022, by Live Science contributor Natalie Grover, with additional reporting by Stephanie Pappas, Live Science Contributor.

Additional resources

• Check out this primer on eating well to manage diabetes in this eating plan from the ADA.
• Learn more about preventing diabetes in this explainer focused on prediabetes, from the Cleveland Clinic.
• Get a deeper look into the science behind diabetes, and the impact of the disease on American society in this book “Cheating Destiny: Living With Diabetes, America's Biggest Epidemic,” by James Hirsch.

Bibliography

Cleveland Clinic. Insulin resistance.
https://my.clevelandclinic.org/health/diseases/22206-insulin-resistance

National Institutes of Health What is Diabetes
https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes

Centers for Disease Control and Prevention Gestational Diabetes and Pregnancy
https://www.cdc.gov/pregnancy/diabetes-gestational.html#:~:text=Gestational%20diabetes%20is%20a%20type,in%20the%20middle%20of%20pregnancy.

National Institutes of Health Symptoms & Causes of Diabetes
https://www.niddk.nih.gov/health-information/diabetes/overview/symptoms-causes 

Mayo Clinic Diabetes
https://www.mayoclinic.org/diseases-conditions/diabetes/symptoms-causes/syc-20371444

Centers for Disease Control and Prevention National Diabetes Statistics Report
https://www.cdc.gov/diabetes/data/statistics-report/index.html

Centers for Disease Control and Prevention Diabetes Symptoms
https://www.cdc.gov/diabetes/basics/symptoms.html

American Diabetes Association Diabetes Symptoms
https://www.diabetes.org/diabetes/type-1/symptoms

National Institutes of Health Diabetic ketoacidosis
https://medlineplus.gov/ency/article/000320.htm 

American Diabetes Association Diagnosis
https://www.diabetes.org/a1c/diagnosis?loc=db-slabnav

National Institutes of Health Insulin, Medicines, & Other Diabetes Treatments
https://www.niddk.nih.gov/health-information/diabetes/overview/insulin-medicines-treatments

National Institutes of Health Achieving Type 2 Diabetes Remission through Weight Loss
https://www.niddk.nih.gov/health-information/professionals/diabetes-discoveries-practice/achieving-type-2-diabetes-remission-through-weight-loss

Lean, M E. J (2019) Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial The Lancet
https://www.thelancet.com/journals/landia/article/PIIS2213-8587(19)30068-3/fulltext

Primavera, M (2020) Prediction and Prevention of Type 1 Diabetes, Frontiers in Endocrinology
https://www.frontiersin.org/articles/10.3389/fendo.2020.00248/full

Colberg, S. R (2010) Exercise and Type 2 Diabetes, Diabetes Care
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC2992225/

Schreiber, A. K (2015) Diabetic neuropathic pain: Physiopathology and treatment, World Journal of Diabetes
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4398900/

Fu, H (2019) Diabetic kidney diseases revisited: A new perspective for a new era, Molecular Metabolism
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6838932/

Hogrebe, N. J (2020) Targeting the cytoskeleton to direct pancreatic differentiation of human pluripotent stem cells Nature Biotechnology
https://www.nature.com/articles/s41587-020-0430-6 

Type 1 diabetes, once referred to as juvenile diabetes or insulin-dependent diabetes, is a chronic condition characterized by high blood sugar, or glucose.  

It occurs when the immune system mistakenly attacks the cells in the pancreas that make the hormone insulin, resulting in the inability of the body to produce enough insulin to keep blood sugars in check. Insulin is crucial for glucose metabolism; it helps shepherd sugar from the bloodstream into the body's cells for energy. Without insulin, glucose builds up in the blood, which, over time, can trigger life-threatening complications. (In people with type 2 diabetes, the body doesn't produce enough insulin, or does not use the insulin efficiently.) 

Type 1 diabetes is frequently diagnosed in children, adolescents or young adults, but it can develop at any age. People with this form of diabetes need to take insulin every day to stay alive. 

In 2019, 37.3 million Americans had diabetes (diagnosed and undiagnosed), of which 1.9 million had type 1 diabetes, according to the American Diabetes Association (ADA).

Causes & risk factors

The exact cause of type 1 diabetes is unclear, according to the National Library of Medicine (NLM). However, scientists think genetics and environmental factors, such as exposure to a virus, can cause the body to mistakenly attack key cells in the pancreas that make insulin.

Some known risk factors for this form of diabetes include a family history of type 1 diabetes, the presence of certain genes and geography; turns out,  the incidence of the disease is higher the farther away one is from the equator, possibly due to UV radiation and vitamin D deficiency, according to several scientific reports, such as a study published in 2017 in the journal Photochemical & Photobiological Sciences. And although the disease can develop at any age, it seems to often strike during two periods: in children between 4 and 7 years old, and in children between 10 and 14 years old, according to the Mayo Clinic.

• Related: Type 3 diabetes: Symptoms, causes and treatments

Symptoms & complications

The inability to produce insulin can result in a constellation of symptoms, which usually appear very quickly over a few days and weeks, according to the National Institute of Diabetes and Digestive and Kidney Diseases. These symptoms may include increased thirst, hunger and urination; blurred vision; fatigue; and unexplained weight loss.

"What we see in children is that they start being hungry and thirsty, and they're urinating a lot," Dr. Spyros Mezitis, an endocrinologist at Northwell Health in New York told Live Science. "They're feeling weak; they're losing weight."

Sometimes, the first sign of type 1 diabetes is a life-threatening condition called diabetic ketoacidosis (DKA), which occurs as a result of drastically low levels of insulin in the body, according to the NLM. Symptoms of DKA may include breath that smells fruity, dry or flushed skin, nausea or vomiting, stomach pain, breathing difficulties, confusion and inability to concentrate. DKA occurs when the body can't use sugar for energy, so it turns to fat instead. As a result of this process, compounds called ketones are released, causing the blood to become acidic and, in turn, toxic. If left untreated, DKA can be deadly.

Over time, uncontrolled blood sugar levels in people with diabetes can lead to a host of complications affecting major organs, triggering serious problems such as heart attack, stroke, blindness and kidney failure.

• Related: Which vegetables are good for diabetics?
• Related: Which fruits are good for diabetics? 

Diagnosis

If a doctor suspects diabetes, they will use a range of blood and other tests to make a diagnosis. For type 1 diabetes, in particular, the favored test is a random blood sugar test. The random blood sugar test measures blood sugar at the time of testing, and fasting is not required. A blood sugar level of 200 milligrams per deciliter (11.1 millimolar/liter) or higher indicates diabetes. But this measure and other blood tests don't discern whether the individual has type 1 or type 2 diabetes. 

Knowing the type of diabetes is crucial because it determines the treatment regimen, according to the Centers for Disease Control and Prevention (CDC). If type 1 diabetes is suspected, doctors may test for certain autoantibodies that attack the body' beta cells. Particular autoantibodies are common in type 1 diabetes, but not in type 2, and include: islet cell antibodies (ICA, against cytoplasmic proteins in the beta cell), antibodies to glutamic acid decarboxylase (GAD-65), insulin autoantibodies (IAA), and IA-2A, to protein tyrosine phosphatase, according to Johns Hopkins Medicine.) 

Other tests that help a doctor to diagnose diabetes, before determining the type, include:

• A fasting plasma glucose test reveals how effectively the body metabolizes glucose and requires the patient to fast for eight hours before taking the test. Normal blood sugar levels vary from person to person, but a normal range for fasting blood sugar is between 70 and 100 mg/dL (3.9 and 5.6 mmol/L), according to the World Health Organization. And a result of more than 126 mg/dL (7.0 mmol/L) of glucose in the blood signals diabetes.
• The oral glucose tolerance test requires the patient to consume an extra-sugary drink. Two hours later, the person undergoes a blood test. A result of 200 mg/dL or greater of glucose in the blood is considered a sign of diabetes.
• The A1C blood test shows average blood glucose over the preceding three months. The test measures glucose attached to hemoglobin, the oxygen-carrying protein in blood. The red blood cells that carry this protein live for about three months, so measuring them at a single time point provides a snapshot of the general level of glucose in the blood. An A1C result of less than 5.7% is normal; between 5.7% and 6.4% suggests prediabetes; and 6.5% or greater indicates diabetes.

Prevention & treatment

Scientists have not yet found a way to prevent type 1 diabetes, but researchers are currently working on ways to cease the destruction of insulin-producing cells in the pancreas in people who are newly diagnosed, the Mayo Clinic says. TrialNet — an international network of institutions and doctors working on type 1 diabetes research — has several clinical trials in the works for preventive measures. For instance, this network is testing whether a drug called Abatacept could delay or prevent the progression of the disease according to TrialNet. Another drug, called teplizumab, was found to delay the progression of type 1 diabetes for a median of two years, according to TrialNet.

Those who develop kidney failure and receive a kidney transplant, will sometimes also receive a transplant of pancreatic islet cells from an organ donor at the same time. Islet transplants may free them from the need to use insulin, potentially for many years, but requires taking lifelong immunosuppressive drugs according to the National Institute of Diabetes and Digestive and Kidney Disorders.

But the vast majority of people with type 1 diabetes require lifelong insulin therapy and will need to monitor their blood sugar levels frequently.

People with type 1 diabetes need to take insulin both to cover basic metabolic functions (called basal insulin) and to regulate the blood sugar produced by eating (called bolus insulin). To handle the blood sugar spikes caused by food, insulin shots are typically timed with meals and, once a routine is established, are done several times per day. Other options for administering insulin include a "pen," which allows for smaller doses (or boluses) of insulin to be injected, and a pump, which is attached to the body and delivers insulin throughout the day through a tiny tube that is inserted just beneath the skin surface, according to the ADA.

Insulin can cause low blood sugar, or hypoglycemia, which may cause feelings of weakness, hunger and headaches. Prolonged and severe low blood sugar can cause seizures, coma and death. 

There are several different types of insulin: Some last from about 18 hours to an entire day (called intermediate and long-acting, respectively); others, called rapid-acting insulin, enter the bloodstream in a few minutes and works most powerfully for an hour or twos; and regular- or short-acting insulin enters the bloodstream in about 30 minutes and is active for 3 to 6 hours, according to WebMD. People with type 1 diabetes may take long-acting insulin, which the body absorbs slowly, to provide the body’s basal metabolic need for insulin, while the rapid-acting insulin is used for meals.  

In 2016, the U.S. Food and Drug Administration approved the use of a so-called "artificial pancreas" — essentially a pump that uses a continuous glucose monitor to detect blood glucose levels and then automatically adjusts insulin dosing in response to those numbers, Live Science previously reported.

At the moment, there is no cure for type 1 diabetes, but research is ongoing. In order to rid someone of type 1 diabetes, the cure would need to both stop the immune system from destroying the body's beta cells and replace the already-lost beta cells successfully, according to the Juvenile Diabetes Research Foundation (JDRF). In 2021, the company Vertex announced a patient with type 1 diabetes was the recipient of a stem-cell therapy to replace their beta cells; and 90 days after the infusion, the person was using 91% less insulin, though the person also needs to continue immunosuppressive therapy to keep the body from killing off those replacement cells.

This article is for informational purposes only and is not meant to offer medical advice.

This article was updated on April 11, 2022, by Live Science contributor Natalie Grover, with additional reporting by Joseph Brownstein, MyHealthNewsDaily contributor.

Additional resources

• Learn more about the latest research on the hunt for a type 1 diabetes cure in this report by The New York Times.
• Read about how the prevalence of type 1 diabetes in American youth is on the rise in this report by the CDC.
• Check out the children's book "Year One with Type One: A True Story of a Boy with Type 1 Diabetes" (Owl Eye Books, 2018), by Mike Suarez, inspired by his son's journey with the disease.

Bibliography

"Statistics About Diabetes," American Diabetes Association
https://www.diabetes.org/resources/statistics/statistics-about-diabetes

"Type 1 diabetes," The Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/type-1-diabetes/diagnosis-treatment/drc-20353017

"Type 1 Diabetes," National Institute of Diabetes and Digestive and Kidney Diseases
https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes/type-1-diabetes

"Type 1 Diabetes," National Library of Medicine
https://medlineplus.gov/genetics/condition/type-1-diabetes/

"What Is Type 1 Diabetes?" Centers for Disease Control and Prevention
https://www.cdc.gov/diabetes/basics/what-is-type-1-diabetes.html

"Diabetic ketoacidosis," National Library of Medicine
https://medlineplus.gov/ency/article/000320.htm

"Diabetes Tests," Centers for Disease Control and Prevention
https://www.cdc.gov/diabetes/basics/getting-tested.html

If men take metformin, a common type 2 diabetes drug, during a critical period of sperm development, their offspring may be more likely to develop birth defects, a large study suggests. 

In particular, the study found that male babies born to fathers who took metformin during this critical period had a higher risk of genital birth defects than babies whose fathers took metformin outside of that key time window or had never taken the drug. The new research was published Monday (March 28) in the journal Annals of Internal Medicine.

"Given the prevalence of metformin use as first-line therapy for type 2 diabetes, corroboration of these findings is urgently needed," Germaine M. Buck Louis, Dean of the College of Health and Human Services at George Mason University in Virginia, wrote in a commentary on the study. "Meanwhile, clinical guidance is needed to help couples planning pregnancy weigh the risks and benefits of paternal metformin use relative to other medications."

More research is needed to understand whether and how metformin affects developing sperm and the resulting embryo, first author Dr. Maarten Wensink, an epidemiologist and biostatistician at the University of Southern Denmark, told Live Science in an email. In the meantime, diabetic men who plan to have children and are interested in alternative medications should consult a doctor before switching prescriptions, he said.

Related: 11 surprising facts about the reproductive system

"In general, metformin is effective, cheap and safe to the person who is taking it. Those are important factors to consider," Wensink said. "Whether or not to take metformin is a decision that every patient should [discuss] with their treating physician."

An increased risk 

Both type 1 diabetes, where the body doesn't produce enough insulin, and type 2 diabetes, where cells show insulin resistance, can impair male fertility. For example, diabetes and the associated high blood sugar can disrupt both testosterone and sperm production, contributing to low sperm counts and erectile dysfunction, and the disease has also been linked to DNA damage in sperm cells, studies suggest. 

But although it's known that persistently elevated blood sugar can undermine male reproductive health, the effects of diabetes drugs on male fertility and birth outcomes remain uncertain, the study authors noted in their report. 

The enormous study included data from more than 1.1 million births in Denmark between 1997 and 2016; these births were cataloged in the nationwide Medical Birth Registry. The research excluded newborns born to mothers diagnosed with diabetes or high blood pressure, so that the analysis could specifically zoom in on how the fathers' diabetes status and medication use affected the offspring.   

To determine the rate of birth defects among these babies, the team then checked the nationwide Patient Registry, which includes all diagnoses made in inpatient and outpatient settings. They also used the Prescription Registry to review all the prescriptions the fathers redeemed during the study period. Sperm development and maturation takes about three months, start to finish, so babies were considered "exposed" to a diabetes drug if their father filled at least one prescription in the three-month window before conception.

The team included three classes of diabetes drugs in this analysis: insulin, metformin and sulfonylureas, a class of drugs used to treat type 2 diabetes that work differently from metformin. Metformin works by decreasing the amount of sugar released into the bloodstream by the liver, while also sensitizing cells to insulin, according to the U.K. National Health Service (NHS). Sulfonylureas both sensitize cells to insulin and drive cells in the pancreas to produce more of the hormone, according to the medical database StatPearls.

Related: 25 scientific tips for raising happy (& healthy) kids

Of the 1.1 million babies included in the analysis, more than 36,500, or 3.3%, had at least one major birth defect, the analysis showed. More than 7,000 babies out of the total had been exposed to one of the three diabetes medications.

The rate of birth defects among insulin-exposed babies matched that of the general population, indicating insulin was not linked to any increase in risk. But babies whose fathers had filled a metformin prescription had a higher rate of birth defects: 5.2% compared with the baseline rate of 3.3%. Among the metformin-exposed infants, the rate of genital birth defects was particularly high compared with the rest of the study population, and these genital birth defects only appeared in male babies.  

Notably, the authors didn't see an increased rate of birth defects among the unexposed siblings of these babies, Buck Louis wrote in her commentary. And in addition, the elevated risk did not affect babies whose fathers took metformin outside the critical three-month window of sperm development.

The number of babies exposed to sulfonylureas was relatively small — about 650 compared with 1,450 in the metformin group — so the authors could not confidently determine whether the drugs carried an associated risk of birth defects, Wensink said. And "many of the fathers who used [sulfonylureas] also used metformin, again complicating the interpretation," he added.

Another limitation of the study is that the data can't reveal how well each father adhered to his diabetes medication or how his blood sugar levels fluctuated through time, Buck Louis wrote. Both of these factors could also influence male fertility and the risk of birth defects, she said.

Although somewhat limited, the study results do hint that metformin increases the risk of birth defects by somehow interfering with sperm development in the father. Future studies in different populations will be needed to confirm the finding and to unpack why the drug might be linked to such a risk, Wensink said.

"Wensink and colleagues' work supports a global call for more conclusive study of the potential risks for paternal use of diabetes drugs to offspring," Buck Louis wrote.

Originally published on Live Science.

They say that being a mother changes you, and they aren't kidding. After birth, a woman’s body can display many physical changes. At no other time in your life will you grow a whole new organ, force your heart to pump 50% more blood, according to the National Library of Medicine, and have alien cells hijack your brain.

While most of those odd changes disappear after birth, a few of them, like your little one, are for keeps. From bigger feet to diabetes, here are 18 things that may never go back to the way they were before you got pregnant.

1. Shoe size

There are two main reasons for the change in shoe size during pregnancy: weight gain and hormones.

The American College of Obstetricians and Gynecologists (ACOG) says that women of a normal weight should gain from 25 to 35 lbs. (11 to 16 kilograms) during pregnancy. "That extra weight that's carried around for the ten lunar months of pregnancy, and even longer, flattens out the [foot's] arch," which is why some women gain about half a shoe size during pregnancy, said Dr. Michael Cackovic, the obstetrics director of cardiac disease and pregnancy at The Ohio State University Wexner Medical Center.

The hormone relaxin also plays a role, according to the Journal of Bone and Joint Surgery. As its name suggests, relaxin helps relax ligaments and bones in the pelvis, so the body can be elastic during childbirth. But relaxin also affects ligaments all over the body, including in the feet, which can make a woman's feet looser and more spread out, said Dr. Leena Nathan, an assistant clinical professor of obstetrics and gynecology at the University of California, Los Angeles.

New moms should get used to sporting a larger shoe size, as these changes are permanent after birth, even after you lose weight and relaxin production stops, Cackovic said.

2. Extra pounds

Speaking of weight gain, while those extra pounds don't have to be permanent, they are for many women.

One in 4 women will hang onto 11 lbs. (5 kg) or more a year after giving birth, Live Science previously reported. After having a baby, a woman will be, on average, 2.5 to 5 lbs. (1 to 2 kg) heavier than she was prior to pregnancy, Kathleen Rasmussen, a professor of maternal and child nutrition at Cornell University, told Live Science. While that's not a large gain, this number can become more significant when repeated  for four or five babies.

3. Vaginal changes

This one shouldn't be a surprise, given the average dimensions of a newborn's head, but women often have vaginal changes postpartum. While the vagina will contract down to almost its original size after birth, most women will have a permanently wider vagina, according to NHS UK..

"There are many factors that contribute, including type of delivery, size of baby, genetic factors [and] being overweight, to name a few," gynecologist Dr. Alyssa Dweck told Live Science.

4. Wee problem

While not all women face one of the more unpleasant problems associated with squeezing an 8-lb. (3.6 kg) human out of their body, giving birth — unfortunately — puts mothers at increased risk for incontinence, or loss of bladder control. That's because vaginal delivery can weaken the muscles needed for bladder control and can damage bladder nerves and supportive tissue, leading to a dropped (prolapsed) pelvic floor, according to the Mayo Clinic.

C-sections can also increase the risk of incontinence, Cackovic said.

Women with incontinence can practice Kegel exercises to strengthen these pelvic floor muscles, he said. There is also at least one Bluetooth-enabled device that enables people to do pelvic floor exercises and get biofeedback with an app on their phone and a small intravaginal device, according to Dweck.

5. Gain a child, lose a tooth

There may be some truth to the saying, "gain a child and lose a tooth." 

A 2008 study of 2,635 women in the American Journal of Public Health found that the more children women had, the more likely they were to have lost teeth. Women between the ages of 35 and 49 with one child had lost an average of two teeth, while women with two children lost an average of four. Meanwhile, women with four or more children had lost an average of seven teeth. It's not clear exactly why, as frequency of dental care didn't seem to be tied to this association.

Other dental problems include enlarged gums and more bleeding from gums during pregnancy because of increased blood flow, Nathan told Live Science. The acid from vomiting, if women have morning sickness, can also wear away the enamel on teeth, Nathan said.

Hormonal changes during pregnancy can also affect the bacteria population, or microbiome, of your mouth, so it's important to practice good dental hygiene during this time, Cackovic said.

"We know that women who don't have good dental health are actually at risk for preterm delivery, so it's very important for women to see their dentists during pregnancy and get their teeth cleaned according to schedule," Nathan said. "If it's not taken care of, it can definitely persist postpartum."

6. Growing and shrinking breasts

A woman's breasts go through some big (and little) changes during and after pregnancy.

"They get bigger at first, because the dormant fat tissue in the breast gets replaced by functional tissue" in preparation for breastfeeding, Cackovic said.

But these larger breasts don't last forever. "After a woman stops breastfeeding, that functional tissue atrophies, because it's not being used anymore," Cackovic said. "And then it's not immediately replaced by fat, because the fat is already gone."

If the woman gets pregnant again, then the process will repeat, and if she gains a lot of weight after a pregnancy, then she'll replace those fat cells in her breasts. "But generally, if somebody is a very fit person and doesn't gain weight, then [her breasts] are going to stay smaller at that point," Cackovic said.

7. Sagging breasts

The technical term for this side effect of pregnancy is ptosis. Once breasts droop, they will not perk up again, because the cause of breast drooping is the stretching of the ligaments and elastin that hold the fatty tissue in place, according to 2008 study in the Aesthetic Surgery Journal.

Once you've had your baby, breastfeeding is unlikely to make breast sagging worse. According to the Mayo Clinic, breastfeeding isn’t the cause of changes in breast size or shape, but weight gain, smoking status and additional pregnancies can worsen droopiness.

8. Lower breast-cancer risk

While breasts may be losing their fight against gravity, here's one fact that may perk you up: Breastfeeding may lower the lifetime risk of developing breast cancer. For every 12 months a woman nurses a baby, her relative risk of breast cancer drops by 4 percent, according to a 2002 review in The Lancet.

Crunching the numbers, the authors suggested that up to half of the breast cancer risk in developed countries could be cut if women had as many babies as they did in developing countries, and two-thirds of that risk reduction was due to breastfeeding. There are, however, other benefits associated with having fewer kids.

9. Stretch marks

Pregnant women might notice pink or red stretch marks on their skin during pregnancy, according to the British Journal of Dermatology. Granted, this condition isn't unique to pregnancy; people can get stretch marks any time they experience a big increase or decrease in weight, Cackovic said.

The good news is that while stretch marks stick around, they do get much lighter over time. "They usually do fade out in one to two years," Cackovic said. However, "if the woman gets pregnant again, or gains or loses a lot of weight again, they may become more pronounced."

10. Hair growth

Women often notice that the hair on their head is lusher and denser during pregnancy, according to the International Journal of Dermatology. But why does this happen?

The answer has to do with hormones. Increased levels of hormones can translate into fewer hairs lost during pregnancy. That's why women may have a thicker head of hair during pregnancy.

After hormone levels return to normal post-pregnancy, that luscious hair goes away. "It's not uncommon for women to complain at six months that their hair is falling out," Cackovic told Live Science. "But [hair loss] is really just a temporary thing and usually resolves by about 12 to 18 months."

11. Skin changes

Pregnancy comes with all kinds of skin changes. For instance, the linea nigra — Latin for "black line" — is a dark, vertical line that runs over the belly to the pubic hair region during pregnancy. According to the Journal of the National Medical Association, new levels of sex hormones is likely to play a role in this change.

Women may also develop the "mask of pregnancy," known as melasma, which are brown patches that color the face. Freckles and moles can also darken during pregnancy.

The linea nigra and melasma are caused by an increase in melanin, the pigment that adds color to your skin and hair, according to ACOG. The dark areas usually fade after the woman gives birth, but some women with melasma can have dark patches for years, ACOG said. Some women with melasma are extra-careful to use sunscreen or wear a hat if they're going outside, and others use skin lighteners after giving birth to address the dark patches, Cackovic said.

12. Diabetes

Gestational diabetes — that is, elevated blood sugar during pregnancy — develops in up to 10 percent of pregnancies in the United States, according to the Centers for Disease Control and Prevention. But the mother's diabetes risk doesn't end when the pregnancy does. After giving birth, up to half of the women who had gestational diabetes will develop type 2 diabetes later in life, Cackovic said.

"Usually, those women already know they're at risk, because they have family members that have diabetes," he said.

If a woman has gestational diabetes, it's important that she maintain a healthy weight and diet, monitor her blood sugar, and get screened for diabetes in the years following her pregnancy so she can be aware if she's becoming prediabetic, according to the Mayo Clinic.

13. Sex drive

After a woman gives birth, it can take a year for her sex drive to return to her normal levels, Cackovic said. Sheer fatigue from caring for a newborn is one reason why. Another has to do with breastfeeding.

If the woman breastfeeds, a decision ACOG supports, then she'll have lower estrogen levels, which can diminish sex drive, Cackovic said.

14. Varicose veins and hemorrhoids

Some pregnant women might notice swollen, sore and blue veins — called varicose veins — on their legs, as well as on the vulva and in the vagina, according to the British Medical Journal. When these sore-feeling veins occur on the rectum, they're called hemorrhoids.

Varicose veins and hemorrhoids develop because the uterus's heavy weight and pressure can reduce blood flow from the lower part of the body, ACOG said. In addition, increased blood flow and a weakening of the blood vessels' lining can contribute to these conditions, Cackovic said.

Usually, varicose veins and hemorrhoids go away within six to 12 months of the birth, Cackovic said. Pregnant women who want to prevent varicose veins from getting worse should exercise regularly, avoid sitting with their legs crossed for a long time, wear support hose, and avoid constipation by eating high-fiber foods and drinking plenty of liquids, ACOG said.

15. Slightly larger uterus

Normally, the uterus is about a pear-size, but during pregnancy, the organ swells to the size of a watermelon, according to the American Pregnancy Association. Afterwards, it deflates and shrinks again over the course of six weeks in a process called involution — but this contraction isn't necessarily 100 percent.

A 1996 study in the journal Ultrasound in Obstetrics & Gynecology found that premenopausal women who had children had slightly larger uteruses than women who had never given birth, even after this postpartum period had passed. However, it's perhaps inaccurate to call it permanent, just long-lasting, as the uterus will then shrink to an even smaller size after menopause.

16. Abdominal separation

One surprisingly common, and ultimately permanent, change associated with pregnancy is a condition called diastasis recti abdominis, according to the journal Current Women’s Health Reviews. It's when the abdominal muscles separate, creating a gap between the stomach muscles.

All women will have this separation at the late stages of pregnancy to make room for the growing belly. But by a year postpartum, somewhere between a third to more than two-thirds of women will retain some separation between their abdominal muscles, various studies suggest.

17. You become a chimera

When a woman is pregnant, her body is filled with cells from her growing baby. But those cells don't all leave with the baby. At least some of those cells travel through the placenta into the rest of the mother's body — where some may remain for the rest of her life. Autopsies of women who had children decades before have found evidence of male DNA in the woman's brains, presumably from gestating their sons, according to a 2012 study in PLOS One.

The purpose of these chimeric cells isn't clear. Some doctors think they can help a mom, while other researchers think the cells are potentially harmful, Live Science previously reported.

18. Wider hips

Some women may notice that their hips are wider following childbirth. But why?

You may think it has to do with the hormone relaxin — largely because relaxin relaxes and softens the joints and ligaments in the pelvis to help the mother push out the baby during labor. But that's likely not the real reason behind wider hips, Cackovic said.

Rather, wider hips are "most probably due to the deposition of fat into areas of the body that have extra fat cells," he told Live Science. In other words, some women get bigger because of accumulating fat cells, not because their hip bones are actually wider.

Additional resources

You can read more about your body after birth by visiting the NHS website. Additionally, to find out what helps your body bounce back after pregnancy, read this article on the John Hopkins website.

Bibliography

"Blood volume changes in normal pregnancy". National Library of Medicine. https://pubmed.ncbi.nlm.nih.gov/4075604/

"Weight Gain During Pregnancy". The American College of Obstetricians and Gynecologists. (2020). https://www.acog.org/clinical/clinical-guidance

"Dimensional changes of the feet in pregnancy". The Journal of Bone and Joint Surgery (2008). http://www.uvm.edu/~istokes/pdfs/footdim.pdf

"Exploring Potential Pathways Between Parity and Tooth Loss Among American Women". American Public Health Associations (2008). https://ajph.aphapublications.org/doi/full/10.2105/AJPH.2007.124735

"The Effect of Breastfeeding on Breast Aesthetics". Aesthetic Surgery Journal (2008). https://academic.oup.com/asj/article/28/5/534/202938

"Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50302 women with breast cancer and 96973 women without the disease". National Library of Medicine (2002). https://pubmed.ncbi.nlm.nih.gov/12133652/

"Stretch marks during pregnancy: a review of topical prevention". British Journal of Dermatology (2014). https://onlinelibrary.wiley.com/doi/abs/10.1111/bjd.13426

"Morphology, growth rate, and thickness of the nail plate during the pregnancy". International Journal of Dermatology (2018). https://onlinelibrary.wiley.com/doi/abs/10.1111/ijd.14152

"The incidence of lower mid-trunk hyperpigmentation (linea nigra) is affected by sex hormone levels". Journal of the National Medical Association (2005). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569341/

"Vulval Varicose Veins in Pregnancy". British Medical Journal (1959). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1992824/?page=1

"Sonographic size of uterus and ovaries in pre- and postmenopausal women". Ultrasound in Obstetrics and Gynecology (1996). https://obgyn.onlinelibrary.wiley.com/doi/abs/10.1046/j.1469-0705.1996.07010038.x

"Diastasis Recti Abdominis-diagnosis, Risk Factors, Effect on Musculoskeletal Function, Framework for Treatment and Implications for the Pelvic Floor". Current Women’s Health Reviews (2019). https://www.ingentaconnect.com/content/ben/cwhr/2019/00000015/00000002/art00003

Insulin resistance is a condition in which the hormone insulin, which regulates blood sugar levels, is unable to do its job. 

Under normal circumstances, glucose (or sugar) enters the bloodstream after the body breaks down food that has been consumed. The pancreas secretes insulin to help glucose (the body's main source of energy) enter muscle, fat and liver cells so the glucose can be used for energy or stored for later use. 

But when a person has insulin resistance, this process goes awry.

"Think of insulin as the key that unlocks the door to their cells. That door needs to be opened in order for glucose to exit the blood into the cell," said Kimber Stanhope, a nutrition research scientist at the University of California at Davis. 

When people are insulin resistant, their pancreas is still making those "keys," but they don't work so well to unlock cells and let in glucose, Stanhope said.

Related: What is normal blood sugar?

In the early stages of insulin resistance, cells start to ignore the signal from insulin to take in glucose from the blood. So the pancreas pumps out more insulin to shepherd glucose into cells and blood sugar mostly stays at a normal level. But over time, the cells stop responding even to those higher levels of insulin. 

"It's not like you suddenly don't respond to insulin," said Calum Sutherland, a professor of molecular and cellular diabetes at the University of Dundee in the U.K. "Maybe in the initial stages, you drop 10% of your response, and then after a few months it may drop 30%, and after a few years it may drop 60%. And so, progressively your body loses its ability to respond appropriately to insulin."

Eventually, the pancreas can't keep up, and blood sugar levels rise. 

People with persistently elevated blood sugar are diagnosed with either prediabetes (in which blood sugar levels are high but not high enough to meet the benchmark for diabetes) or type 2 diabetes, which can lead to a host of life-threatening complications if left untreated, according to the CDC. In 2019, about 96 million U.S. adults had prediabetes, according to data from the Centers for Disease Control and Prevention. (CDC)

Causes of insulin resistance

It's not totally clear what causes insulin resistance, according to the American Diabetes Association (ADA).

However, several risk factors have been linked with insulin resistance, including being overweight or obese and having a family history of type 2 diabetes, according to the CDC. 

Some researchers suspect that extra fat tissue may cause inflammation, physiological stress or other changes that contribute to insulin resistance, according to the ADA. 

(Separately, insulin resistance also contributes to weight gain, leading to a vicious cycle.)

Although being overweight is a risk factor for insulin resistance and diabetes, some people with insulin resistance or diabetes are not overweight. In fact, about 10% to 15% of people with type 2 diabetes are at a healthy weight, according to WebMD. 

Inactivity is also a risk factor for insulin resistance, according to the National Diabetes Information Clearinghouse. Inactivity may lead to insulin resistance because muscle tissue uses more glucose than other types of tissue, and muscle becomes better at taking up sugar after exercise. People who exercise infrequently do not benefit from this effect. 

Aging is also tied to insulin resistance, because people typically lose muscle mass as they age, according to a 2021 review article in the journal Comprehensive Physiology. Lower muscle mass means fewer cells that can take in large amounts of glucose.

Symptoms and diagnosis

Most people in the early stages of insulin resistance have no symptoms and no idea that they are on the pathway to disease. And doctors do not diagnose insulin resistance — also referred to as impaired insulin sensitivity —  it is usually only measured in research studies.

"We don't have a threshold where we say someone is insulin resistant," Sutherland told Live Science.

Doctors may instead diagnose a related condition known as metabolic syndrome, which includes high blood sugar, high cholesterol and high blood pressure levels and excess belly fat, according to the National Heart, Lung and Blood Institute. 

Many people only find out about their blood sugar-processing problems when they start showing symptoms of prediabetes and type 2 diabetes, which is a lifelong, progressive condition. These symptoms include increased thirst, hunger and urination, blurred vision, and slow healing of cuts and sores, according to the Cleveland Clinic. 

To diagnose high blood sugar, doctors may order an A1C blood test, which measures a person's average blood glucose over the preceding three months, or the fasting plasma glucose test, which reveals how effectively the body metabolizes glucose after a person has fasted for eight hours.

Doctors may also order tests that help to diagnose other conditions associated with insulin resistance, such as cardiovascular disease and polycystic ovary syndrome (PCOS), which is a hormonal disorder that can affect women of reproductive age, according to the Cleveland Clinic.

Insulin resistance and diet

Insulin resistance is common nowadays in part because of our Western diets, Sutherland told Live Science. (Western diets are typically high in calories, refined grains and ultraprocessed foods and low in fiber.)

Although no single diet has shown to be most effective, certain diets may improve insulin sensitivity. For instance, diets low in simple or processed sugars but high in fiber and complex carbohydrates may be helpful, according to a review study published in 2019 in the journal Advances in Clinical and Experimental Medicine.

The Mediterranean diet — which emphasizes eating vegetables and fruits, nuts, whole grains, fish and extra virgin olive oil— has been shown in several studies to reduce insulin resistance.

And the Dietary Interventions to Stop Hypertension (DASH) diet — which emphasizes vegetables and fruits, low-fat dairy foods and limits sweets, salt and saturated fats — has also been associated with lower insulin resistance, several studies show.

Can insulin resistance be reversed?

In some people, insulin resistance can be reversed, said Richard Mackenzie, a researcher who studies insulin resistance and metabolism at the University of Roehampton in the U.K. 

"We know with weight/fat loss that insulin resistance improves," Mackenzie told Live Science in an email. "We know that gastric bypass surgery [a type of weight loss surgery] can completely reverse insulin resistance in the matter of days."

To aid such weight loss, doctors may recommend eating fewer processed carbohydrates and less unhealthy fat, sugar, red meat and processed starches, according to the Cleveland Clinic. 

The Diabetes Prevention Program, a long-running study funded by the National Institutes of Health, found that for people at high risk of developing diabetes, losing 5% to 7% of their starting weight helped reduce their chances of developing the disease. (Participants in the study lost weight by changing their diet and being more physically active.)

Physical activity — both high-intensity interval training and moderate physical activity — also increases glucose energy usage and improves muscle insulin sensitivity, a clinical trial published in 2020 found.

Some people with insulin resistance may benefit from a drug called metformin, which reduces the amount of glucose the liver makes and prompts the muscles and other tissues to take up more blood sugar. The results of the Diabetes Prevention Program showed that metformin worked best for younger adults, people with obesity and people with a history of gestational diabetes. 

This article is for informational purposes only and is not meant to offer medical advice.

This article was updated on Feb. 8, 2022, by Live Science contributor Natalie Grover.

Additional resources

• Check out this report by Yale on the latest research linking insulin resistance to fatty liver disease.
• Learn more about metformin in this review published by the Mayo Clinic.

Bibliography

American Diabetes Association. Understanding insulin resistance. https://www.diabetes.org/healthy-living/medication-treatments/insulin-resistance

Centers for Disease Control and Prevention. Insulin resistance and diabetes.
https://www.cdc.gov/diabetes/basics/insulin-resistance.html

Cleveland Clinic. Insulin resistance. https://my.clevelandclinic.org/health/diseases/22206-insulin-resistance

National Institute of Diabetes and Digestive and Kidney Diseases. Diabetes Prevention Program (DPP). U.S. Department of Health and Human Services, National Institutes of Health. https://www.niddk.nih.gov/about-niddk/research-areas/diabetes/diabetes-prevention-program-dpp 

National Institute of Diabetes and Digestive and Kidney Diseases.Insulin resistance & prediabetes. U.S. Department of Health and Human Services, National Institutes of Health.https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes/prediabetes-insulin-resistance#:~:text=Insulin%20resistance%20is%20when%20cells,help%20glucose%20enter%20your%20cells

Additional reporting by Amanda Chan, Live Science contributor

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Insulin-producing cells in the pancreas carry a "death receptor" that, when activated, causes the cells to self-destruct. This cellular self-destruct button may in turn contribute to the development of type 1 diabetes, according to a new study in mice and human tissues.

The findings also suggest a potential way to rescue some of these cells from certain death — by locking those cellular doorways, according to a new study.

Type 1 diabetes is an autoimmune disorder where the immune system attacks the insulin-producing beta cells in the pancreas. A hallmark of type 1 diabetes is the death of these beta cells, but exactly why those cells die isn't entirely clear; scientists suspect multiple mechanisms are at play, according to a 2016 report in The Journal of Autoimmunity. 

Related: 12 amazing images in medicine 

The new study identifies the death receptor, called transmembrane protein 219 (TMEM219), which sits within the outer membrane of beta cells, as a key player in this process, according to a statement. A protein called insulin-like growth factor binding protein 3 (IGFBP3) binds to the portion of the death receptor that juts off the cell surface, and by doing so, it sets off a chain of events inside the cell. This chain of events spells certain doom for the beta cell — it triggers apoptosis, or cellular suicide, the new study found.

In several laboratory studies with mice, the researchers tried different ways of preventing this chain of events from unfolding; the mice used in the study were genetically modified such that they're prone to type 1 diabetes. 

In one experiment, for example, the team deleted the death receptor altogether using genetic modification, and in another they blocked the receptor using a protein that had been modified for that purpose. The team found that, when they temporarily blocked the death receptor in mice, a larger number of beta cells survived than did in untreated mice, and insulin production increased. This, in turn, delayed or prevented the onset of diabetes in the mice. When the team blocked the death receptor for an extended period of time, the animals' beta cells increased in number. 

The team also ran experiments with human beta cells. Applying IGFBP3 to the tissues triggered rampant beta cell death, but by blocking the death receptors on the cells, the researchers could stop this damage from occurring and allow the cells to keep producing insulin.

Supporting what they found in the laboratory, the team also found that people diagnosed with diabetes and those at high risk of diabetes both carried high levels of IGFBP3, as compared with those who did not have diabetes. This was also true of diabetic and prediabetic mice, compared with healthy mice, they found. 

"We think that in disease, IGFBP3 production may be increased, so there is a loss of beta cells," Dr. Paolo Fiorina, a research associate and assistant professor at Harvard Medical School and Boston Children's Hospital, said in the statement. Fiorina is the founder of a biotechnology company, Enthera, that's developing treatments to block the beta cell death receptor. The first human trials of such a treatment could begin by fall 2022, according to the statement. 

"The common thought for type 1 diabetes is that it [is] autoimmune," Fiorina said. "But immunotherapy doesn't completely cure diabetes." We think that IGFBP3 acts as a "betatoxin" and disrupts the normal function of beta cells, and thus also contributes to the development of diabetes, he said. 

The new study was published Thursday (Feb. 3) in the journal Nature Communications. 

Originally published on Live Science. 

Scientists may be zeroing in on why catching COVID-19 raises people's risk of developing diabetes, Science News reported.

Several studies have hinted that COVID-19 infections can trigger diabetes in some people, but exactly why remained a mystery, Live Science previously reported. The new diabetes cases linked to COVID-19 include both type 1 diabetes, in which the body attacks the cells in the pancreas that produce insulin, and type 2 diabetes, in which the body still produces some insulin, though often not enough, and its cells don't respond properly to the hormone. Insulin lowers the amount of glucose, or sugar, in the blood by telling cells to absorb that sugar and use it as fuel.

Some evidence suggests that SARS-CoV-2, the virus that causes COVID-19, may infiltrate insulin-producing cells in the pancreas. That would mean the virus sends some people's blood sugar levels skyrocketing by damaging these cells and reducing how much insulin they secrete. But more recent research suggests that, in many COVID-19 patients with ultrahigh blood sugar, these pancreatic cells are still working fine — so there must be another explanation, Science News reported.  

Related: What is normal blood sugar? 

The recent work, led by Dr. James Lo, a physician-scientist and associate professor of medicine at Weill Cornell Medicine in New York City, suggests that blood sugar spikes  may be tied to low levels of a hormone called adiponectin. Adiponectin sensitizes cells to insulin, essentially working synergistically with insulin to regulate blood sugar levels. The hormone is produced primarily by fat cells, but in patients with severe COVID-19 and high blood sugar, fat cells seem to malfunction and produce far less adiponectin than normal, Lo and his colleagues found. 

The severe coronavirus infections the team studied were associated with acute respiratory distress syndrome, or ARDS, where fluid builds up in the air sacs of the lungs. The team compared this group of COVID-19 patients to other people with ARDS, who had developed the syndrome from different infections. The incidence of super high blood sugar was similar between the two groups, but only the COVID-19 patients had low adiponectin, hinting that the coronavirus somehow affected the hormone, the researchers reported in a recent study, published in 2021 in the journal Cell Metabolism. 

And adiponectin wasn't the only fat-derived hormone that went helter-skelter in these COVID-19 patients, the team found. This suggests that, in general, the function of their fat cells had been compromised.

This malfunction, in turn, may drive COVID-19 patients to become insulin resistant, because adiponectin is no longer sensitizing their cells to insulin, the team concluded.

Studies suggest that SARS-CoV-2 can infect fat cells directly, Live Science previously reported, and Lo's team confirmed this finding in experiments with hamsters and cells in lab dishes. This viral infiltration of fat cells could mess up their hormone production. In addition, infections drive inflammation, which may also undermine fat cells' ability to produce adiponectin, Science News reported. 

The team's work adds to a growing body of evidence that SARS-CoV-2 damages fat cells and alters their function and that these functional changes may contribute to the onset of diabetes in some people. That said, on its own, the work cannot prove that a dip in fat-derived hormones is triggering COVID-19-related diabetes; more work will be needed to confirm this underlying mechanism. 

Read more about the research in Science News. 

Originally published on Live Science. 

The coronavirus that causes COVID-19 can infect insulin-producing cells in the pancreas, reducing their ability to secrete insulin and sometimes causing cell death, a new study suggests.

Damaging these insulin-producing cells, known as beta cells, can potentially worsen symptoms of diabetes, particularly type 1 diabetes, wherein the pancreas already makes little to no insulin, according to the study authors. "If you imagine that there are some patients who already have diabetes, if the virus comes in and nails the remaining beta cells you have, that's not good," said co-senior author Peter Jackson, a professor in the department of microbiology and immunology at Stanford University School of Medicine. 

In addition, some studies suggest that severe COVID-19 may trigger diabetes in people with no previous history of the condition, again raising the possibility that the virus infects beta cells, Live Science previously reported. This trend is still being investigated, but given the new data, Jackson said that he thinks the virus may sometimes induce diabetes by injuring beta cells; this would be most likely to occur when people with prediabetes, or other health conditions that raise the risk of diabetes, develop a severe case of COVID-19. 

Related: 20 of the worst epidemics and pandemics in history 

People with either type 1 or type 2 diabetes — where the body makes some insulin but the tissue can't take it up due to insulin resistance — face a greater risk of developing severe COVID-19 symptoms than the general population, according to the Centers for Disease Control and Prevention (CDC). In general, people with diabetes are more likely than those without the disease to experience complications when infected with any virus, since the condition can impair immune function. 

That said, no one knew whether SARS-CoV-2, the virus that causes COVID-19, can directly attack the pancreas, Jackson said. 

To probe this question, Jackson and his colleagues ran experiments on pancreatic tissue from organ donors, nine of whom had died from severe COVID-19 infections and 18 who died of other causes and tested negative for the virus. In the first group, they found SARS-CoV-2 had directly infected the beta cells of some individuals, and in several lab dish experiments, they found that the virus could infect, damage and kill beta cells drawn from the other donors who died from non-COVID-19 causes, according to a report published May 18 in the journal Cell Metabolism. 

However, even with this new evidence, the central question of whether SARS-CoV-2 directly infects beta cells in vivo remains unsettled, said Dr. Alvin Powers, director of the Vanderbilt Diabetes Center in Nashville, who was not involved in the study. The new study shows that pancreatic cells can be infected in a lab dish, but the same has not been definitively shown in humans, he said; to reach a solid conclusion, scientists will need to examine many more pancreas samples from patients who died of COVID-19.

In regards to the reports of COVID-19 triggering diabetes, "we know that people who have borderline diabetes, or prediabetes, when they get [critically] ill with anything, with pneumonia, with a heart attack, with a stroke … diabetes sometimes appears," Powers told Live Science. So it's possible that there may be uptick in diabetes cases, "not because of direct toxicity from the SARS-CoV-2 virus," but because critically ill people sometimes develop diabetes. In general, reports of COVID-19-related diabetes have been conflicting and still warrant further investigation, Powers wrote in a recent commentary, published April 7 in The Lancet. 

How the virus might break into beta cells 

To determine whether SARS-CoV-2 infects beta cells, the first step is to figure out how the virus would infiltrate those cells in the first place. 

The virus primarily uses a receptor protein called ACE2 to sneak into cells, but several other proteins on the cell surface appear to help prime the virus to plug into ACE2, Powers said. For a recent study, published Dec. 1, 2020, in Cell Metabolism, Powers and his colleagues went hunting for ACE2 and one of these proteins, called transmembrane serine protease 2 (TMPRSS2), in beta cells, but found little of either.  In another independent study, published in the same journal, researchers reached the same conclusion, making it seem like SARS-CoV-2 had few doorways into beta cells. 

"The controversy comes from, 'Hey there's not so much receptor here, so it must not be that the virus infects beta cells,'" said co-senior author Raul Andino, a professor in the department of microbiology and immunology at the University of California, San Francisco. However, there's a question as to how much ACE2 the virus needs to break into cells, and still other proteins may help boost its ability to latch onto the ACE2 receptor, Andino said. 

For instance, receptor proteins called neuropilin 1 (NRP1) and transferrin receptor (TFRC) have both been linked to SARS-CoV-2 infection; normally, the former binds to various growth factors and the latter helps import iron into cells, but studies have found that both receptors may be exploited by the coronavirus. The team looked for these proteins, as well as ACE2 and TMPRSS2, in beta cells from five COVID-negative organ donors. 

"We isolate islets [groups of pancreatic cells] from human cadavers as they come in," Jackson said, noting that the tissue must be collected and used quickly to be useful for experiments.

As in previous studies, they found low levels of ACE2 and TMPRSS2 in beta cells from the donors, but interestingly, they found an abundance of NRP1 and TRFC. Compared with alpha cells, another kind of pancreatic cell, beta cells expressed far more NRP1 and TRFC, hinting that the virus might show a selectivity for the beta cell if it does infect the pancreas.

Related: Why COVID-19 kills some people and spares others. Here's what scientists are finding. 

The team then isolated more islets from COVID-negative donors and exposed the tissue to SARS-CoV-2 in the lab. After several days, they exposed the cells to antibodies that latch onto part of the coronavirus, to see which cells had been infected, and found evidence of SARS-CoV-2 mostly in beta cells. They found that they could somewhat block this infection by blocking the NRP1 receptor with a small molecule called EG00229. This fact hints that NRP1 may be key to the coronavirus entering beta cells, Jackson said.

"Imagine you're trying to catch a basketball: A one-handed catch is tricky and … you flub the ball a lot of the time. A two-hand catch is a much more accurate and efficient event," he said. To infect cells, a structure on the coronavirus called the spike must plug into ACE2; in this analogy, NRP1 may be helping to "catch" the coronavirus and insert the spike, despite there being relatively few of ACE2 receptors available, he explained. Some studies suggest that NRP1 grabs onto a specific fragment of the spike, and that blocking this interaction somewhat hobbles the virus's ability to infect cells in culture, according to a November report in the journal Science. 

The team also found that infected beta cells produced significantly less insulin than uninfected cells when exposed to a meal's worth of glucose; and in infected cells, molecular signals related to cell death began to spike. These effects could again be blocked with EG00229, underscoring the potential importance of NRP1 to infection.

After seeing that the virus could infect beta cells from COVID-negative donors, the team wanted to see if the virus cropped up in people who had died of COVID-19. They found coronavirus genetic material in seven out of the nine donors' pancreases. Using antibodies, as in the previous experiments, the team confirmed that SARS-CoV-2 appeared in four out of the seven donors' beta cells; inside those beta cells, they also found genetic instructions coding for the spike protein.

The other three donors' pancreases showed extensive damage, resulting from digestive enzymes that quickly eat away at the organ after death, the authors noted in their report. So it may be that the antibody test came back negative for three donors due to the severity of that damage, Jackson suggested. On the other hand, the negative tests could be accurate, as not all patients with severe COVID-19 necessarily have infected beta cells.

"We would really need to power a much larger study to get a real number as to the infection rate in pancreatic beta cells for patients with severe COVID," Jackson said.

The study raises other questions. Assuming the virus attacks beta cells in living people as it does in lab dishes, how does the virus first reach the pancreas? The onset of pneumonia may help the virus escape the airways and trigger secondary infection elsewhere, such as in the pancreas, but for now that's unclear, Jackson said. The study also only included people with severe disease, so it's unclear whether pancreatic infection ever takes place in mild COVID-19 infections. 

And if and when the virus pervades the pancreas, "how does infection of the pancreas correlate with … decreases in insulin?" Andino said. The team observed that in the lab dish, beta cells produced less insulin after infection, but the extent of that decrease may be different in a living person. "I think that's a critical question, obviously … and that's something to me that the paper does not address." 

In addition, more research will be needed to understand the role of the immune system in pancreatic infection, he noted. In theory, direct infection could trigger extensive inflammation in the pancreas, causing extra damage, and in people susceptible to type 1 diabetes, this could trigger or worsen the autoimmune attack on the the organ. But for now, that's all speculation, Andino said. 

Given the limitations of the lab dish study, researchers need large studies of well-preserved pancreases from people who died COVID-19 to confirm the organ is directly infected, Powers said. "Whether or not their approach to infecting cells mimics what happens when a person has SARS-CoV-2 infection is not clear."

Originally published on Live Science.

In a small, early study, a vaccine for type 1 diabetes helped preserve the body's natural production of insulin, at least in a subset of newly diagnosed patients.

In patients with type 1 diabetes, the body's immune system attacks the beta cells in the pancreas that produce insulin, a hormone that's necessary for cells to absorb glucose from the bloodstream. These patients need lifelong insulin injections to stay alive. 

And because so many hidden factors inside the body can affect how much insulin a person needs, people who are insulin-dependent often have high and low blood sugar. High blood sugar, or hyperglycemia, damages the organs over the long term, while low blood sugar, or hypoglycemia, can lead to seizures or death in the short term.

Related: 5 ways gut bacteria affect your health

In the current study, the researchers wanted to test whether a vaccine might be able to stop or slow the destruction of these insulin-producing beta cells.

"Studies have shown that even an extremely small production of insulin in the body is highly beneficial for patient health," lead author Dr. Johnny Ludvigsson, a senior professor in the Department of Biomedical and Clinical Sciences at Linköping University in Sweden, said in a statement. "People with diabetes who produce a certain amount of insulin naturally do not develop low blood sugar levels, hypoglycemia, so easily."

Ludvigsson and his team developed a vaccine made from glutamic acid decarboxylase (GAD), a protein anchored to the surface of beta cells that many people with type 1 diabetes form antibodies against. (The treatment is called GAD-alum).

People with certain versions of immune system genes, known as human leukocyte antigen (HLA) genes, are at higher risk of developing type 1 diabetes. Several HLA types increase the risk of the autoimmune disorder, but one genetic variant, known as "HLA-DR3-DQ2," exposes a form of the GAD protein (GAD65) to the immune system on the surface of beta cells, according to the statement. This triggers the immune system to produce antibodies against the protein and target the beta cells for destruction. 

The researchers wanted to see if a vaccine that exposed the body to more GAD would help the immune system better tolerate the body's natural GAD65 and thus stop attacking the insulin-producing cells.

For the phase 2 clinical study, the researchers recruited 109 patients between the ages of 12 and 24 who had been diagnosed with type 1 diabetes within the past six months. About half of the patients carried the  HLA-DR3-DQ2 gene variant. 

The researchers divided the participants into two groups: Half of the participants, assigned randomly, were given three shots of the vaccine into their lymph nodes, each one month apart, and the other half were given a placebo. 

The researchers analyzed how much natural insulin the participants produced at the start of the study and after 15 months. They also analyzed changes to long-term blood sugar levels and how much supplementary insulin they needed to take daily.

As a whole, there was no difference in the treatment and placebo groups. But the subset of patients who had the HLA-DR3-DQ2 variant did not lose insulin production as quickly as other patients did. 

"Treatment with GAD-alum seems to be a promising, simple and safe way to preserve insulin production in around half of patients with type 1 diabetes, the ones who have the right type of HLA," Ludvigsson said. "This is why we are looking forward to carrying out larger studies, and we hope these will lead to a drug that can change the progress of type 1 diabetes."

The study, published online May 21 in the journal Diabetes Care, was funded by the pharmaceutical company Diamyd Medical AB, which was also involved in planning and collecting data in the trial, the Swedish Child Diabetes Foundation and the Swedish Diabetes Foundation.

Originally published on Live Science.

Some COVID-19 patients in India have developed a rare and potentially fatal fungal infection called mucormycosis, also known as "black fungus," according to news reports.

Mucormycosis is caused by a group of molds called mucormycetes, which grow in soil and decaying organic matter, such as rotting leaves and wood, according to the Centers for Disease Control and Prevention (CDC). 

"It is ubiquitous and found in soil and air and even in the nose and mucus of healthy people," Dr. Akshay Nair, a Mumbai-based eye surgeon, told BBC News. The mold can enter the body through cuts and other abrasions in the skin, or the infection can take hold in the sinuses or lungs after people breathe in the fungal spores. Once inside the body, the fungus can sometimes spread through the bloodstream and affect other organs, such as the brain, eyes, spleen and heart.

Related: 20 of the worst epidemics and pandemics in history

Most commonly, mucormycosis strikes those with weakened immune systems, including those with diabetes and those taking medicines that suppress immune activity, according to the CDC. Now, an increasing number of COVID-19 patients in India appear to be contracting the infection, The New York Times reported.

For instance, in the state of Maharashtra, where Mumbai is located, 200 individuals caught mucormycosis after recovering from COVID-19, and eight have died from the black fungus, the Times reported, citing local news coverage. Cases are also appearing in the capital city of Delhi and in the state of Gujarat, where the state government has ordered 5,000 doses of the antifungal drug amphotericin B to treat the disease.

"We have heard that in some areas, people who are COVID-infected or recovered suffer from mucormycosis, but there is not a big outbreak of it," Dr. V.K. Paul, head of India's Covid task force, said at a press conference last week, according to the Times. "We are watching and monitoring."

The rise in cases may be connected to the use of steroids in hospitalized COVID-19 patients, since the drugs suppress the immune system, BBC News reported. And those with diabetes start out at increased risk for the infection, even before taking steroids. "Diabetes lowers the body's immune defenses, coronavirus exacerbates it, and then steroids which help fight COVID-19 act like fuel to the fire," Nair told BBC News. 

In addition, many families have had to treat relatives for COVID-19 at home, meaning people may become exposed to the mold after receiving medicine or oxygen therapy in less-than-sterile conditions, the Times reported.

Nair saw several dozen Mumbai-based patients with the black fungus in April; many of them had diabetes and had recently recovered from COVID-19 at home, since hospitals were overrun with patients, BBC News reported. Eleven of the patients needed to have an eye surgically removed due to the fungal infection, since the mold can easily spread from the eyes to the brain.

In the early stages of infection, patients often present with a stuffy or bleeding nose; swollen eyes; droopy eyelids; or blurred vision, BBC News reported. Black patches can also appear on the skin around the nose.

Read more about the cases of mucormycosis in The New York Times and BBC News. 

Originally published on Live Science.

Emerging data hint that COVID-19 can trigger diabetes in some people, although the exact reason remains unknown.

Scientists around the world noticed an uptick in new diabetes cases last year and, in particular, saw that some COVID-19 patients with no history of diabetes were suddenly developing the condition, Scientific American reported. The trend prompted many research groups to launch studies of the phenomenon; for instance, researchers at King's College London in England and Monash University in Australia established the CoviDiab Registry, a resource where doctors can submit reports about patients with a confirmed history of COVID-19 and newly diagnosed diabetes. 

More than 350 clinicians have submitted reports to the registry, The Guardian reported. They've reported both type 1 diabetes, in which the body attacks the cells in the pancreas that produce insulin, and type 2 diabetes, in which the body still produces some insulin, though often not enough, and its cells don't respond properly to the hormone.

Related: 20 of the worst epidemics and pandemics in history 

"Over the last few months, we've seen more cases of patients that had either developed diabetes during the COVID-19 experience or shortly after that," Dr. Francesco Rubino, a professor and chair of metabolic and bariatric surgery at King's College London, told The Guardian. "We are now starting to think the link is probably true — there is an ability of the virus to cause a malfunctioning of sugar metabolism."

Other studies have found a link between COVID-19 and diabetes.

For example, a review of eight studies, which included more than 3,700 hospitalized COVID-19 patients, showed that roughly 14% of these patients developed diabetes, Scientific American reported. A preliminary study of 47,000 U.K. patients found that 4.9% developed diabetes, The Guardian reported.

"We clearly see people without previous diabetes developing diabetes," Dr. Remi Rabasa-Lhoret, a physician and metabolic diseases researcher with the Montreal Clinical Research Institute, told CTV News. "It is highly probable that COVID-19 is triggering the disease." 

The big question is why, and scientists have several theories.

It may be that SARS-CoV-2, the virus that causes COVID-19, directly attacks insulin-producing cells in the pancreas, Scientific American reported. Alternatively, the virus may damage these cells indirectly by infecting other parts of the pancreas or the blood vessels that supply the organ with oxygen and nutrients. Still another theory suggests that the virus infects other organs involved with blood sugar regulation, such as the intestines, and somehow undermines the body's ability to break down glucose, more generally.  

Other types of viruses — such as certain enteroviruses, which cause various conditions, including hand, foot, and mouth disease — have been linked to diabetes in the past, The Guardian reported. In addition, a subset of patients who caught the coronavirus SARS-CoV, which caused outbreaks of severe acute respiratory syndrome in the early 2000s, also developed diabetes afterward, Dr. Mihail Zilbermint, an endocrinologist and associate professor at the Johns Hopkins School of Medicine, told CTV News.

In general, acute viral infections can spark severe inflammation in the body, and in response, the body produces stress-related hormones, such as cortisol, to tamp down that inflammation. Stress hormones can cause blood sugar levels to spike, and that rise doesn't always subside after the infection clears, Scientific American reported. 

In addition, COVID-19 patients are often treated with steroid medications, such as dexamethasone, which can also drive up blood sugar levels. Therefore, it's possible that these steroids also contribute to the onset of diabetes in COVID-19 patients, Zilbermint told CTV News. Steroid-induced diabetes may subside after the patient stops taking the drugs, but sometimes, the condition becomes chronic, according to Diabetes.co.uk.

Another factor contributing to uncertainty about the link, however, is how many of the patients already had prediabetes, meaning they have higher-than-average blood sugar levels, when they caught COVID-19. "It's possible that [a] patient lives with prediabetes for many years and didn't know that," Zilbermint told CTV News. "Now they have COVID-19 infection, and the infection is pushing them towards developing diabetes."

Scientists aren't sure whether the people who developed diabetes after getting COVID-19 will have the condition permanently, Rabasa-Lhoret told CTV News. In at least some patients who developed diabetes after a SARS infection, their diabetic symptoms eventually subsided and their blood sugar returned to normal levels after the infection, according to a 2010 report in the journal Acta Diabetologica. Patients infected with SARS-CoV-2 may experience similar, short-lived diabetic symptoms, but this will need to be confirmed with further studies.

Originally published on Live Science.