Diabetes appears to be a disease written deeply in human genes, a feature millions of years old, which can emerge yet also retreat through the influence of environmental forces such as diet, a new study suggests.
Researchers looked at how obesity, in particular, can trigger the onset of Type 2 diabetes in both mice and humans by manipulating how genes are expressed.
They found that obesity, in effect, can change the chemical tags associated with DNA, called the epigenome. These epigenetic changes modify how genes behave and can alter the production of proteins necessary for proper metabolism and secretion of insulin, the hormone that controls blood sugar levels.
The good news is that diseases brought on by such epigenetic changes can be reversed, the scientists at Johns Hopkins University in Baltimore said in their study, published Jan. 6 in the journal Cell Metabolism.
The study may help explain why Type 2 diabetes, a disease that was hardly seen a few generations ago, now affects more than 300 million adults worldwide, with some populations far more affected than others — a conspiracy of both genetic and epigenetic factors. [8 Reasons Our Waistlines Are Expanding]
In people with Type 2 diabetes, the body has lost either the ability to produce enough insulin, or the ability to respond to the insulin that is produced. Insulin is the hormone that triggers the body's cells to take up sugar from the bloodstream, so in people with Type 2 diabetes, the level of sugar in the blood rises too high.
It is well established that people who are obese are at increased risk of developing Type 2 diabetes, so the Hopkins scientists first studied obese mice to understand how obesity is related to the disease. The mice in the study were clones — all had identical genetics. The researchers found that the mice placed on a high-fat diet grew obese and diabetic; mice on a regular diet stayed lean and healthy. This much was expected.
Yet although the mice started life with identical genes, it was clear that the lean and obese mice had radically different gene expression as adults. An analysis of DNA isolated from their fat cells revealed changes in the epigenome: at certain sites along their DNA, chemical tags called methyl groups were present in the lean mice but missing in the obese mice; at other sites, vice versa. These methyl groups prevent genes from making proteins.
The scientists then looked at a dataset of obese people who underwent gastric bypass surgery, and, to their surprise, found nearly the exact same pattern of epigenetic changes at key sites in DNA isolated from their fat cells.
"Mice and humans are separated by 50 million years of evolution, so it's interesting that obesity causes similar epigenetic changes to similar genes in both species," said Dr. Andrew Feinberg, director of the university's Center for Epigenetics, who led the study.
The findings mesh nicely with other recent discoveries about the role of diet in the development of diabetes.
A study published in April 2012 in The New England Journal of Medicine found that 75 percent of people with diabetes who underwent gastric-bypass surgery saw a reversal of their disease. The Hopkins study supports this by revealing how the epigenome in obese patients becomes more like the epigenome in lean people after this weight-loss surgery.
A study published in August 2014 in Cell Metabolism found that grizzly bears essentially become diabetic during hibernation, and then "recover" when they awaken. The bears' diabetes is induced by the accumulation of fat in the months preceding their winter sleep. Once in a diabetic state, insulin stops working, and, in the absence of more food while hibernating, the insulin resistance allows the bears to effectively break down their fat stores for energy.
This finding points to the idea that diabetes is a feature encoded in our DNA that can have evolutionary advantages in a feast-or-famine world, the researchers said.
"It's likely that when food supplies are highly variable, these epigenetic changes help our bodies adapt to temporary surges in calories," Feinberg said. "But if the high-calorie diet continues over the long term, the same epigenetic pattern raises the risk for disease."
Feinberg stressed, however, that the new findings highlight the "complementary nature of genetics and epigenetics in disease." Diet is still the main contributor to type 2 diabetes, he said.
Some of the epigenetic changes that the scientists discovered were associated with genes already known to raise diabetes risk. Many more were tied to genes not linked conclusively to the disease but rather metabolism in general.
Together, they offer "new potential targets for treating Type 2 diabetes," said G. William Wong, an associate professor of physiology at Johns Hopkins and a co-author on the paper. The study also suggests that researchers could develop an epigenetic test to identify people on the path to diabetes much earlier than can now be done.
Follow Christopher Wanjek @wanjek for daily tweets on health and science with a humorous edge. Wanjek is the author of "Food at Work" and "Bad Medicine." His column, Bad Medicine, appears regularly on Live Science.
Live Science newsletter
Stay up to date on the latest science news by signing up for our Essentials newsletter.
Christopher Wanjek is a Live Science contributor and a health and science writer. He is the author of three science books: Spacefarers (2020), Food at Work (2005) and Bad Medicine (2003). His "Food at Work" book and project, concerning workers' health, safety and productivity, was commissioned by the U.N.'s International Labor Organization. For Live Science, Christopher covers public health, nutrition and biology, and he has written extensively for The Washington Post and Sky & Telescope among others, as well as for the NASA Goddard Space Flight Center, where he was a senior writer. Christopher holds a Master of Health degree from Harvard School of Public Health and a degree in journalism from Temple University.
Stolen remains of Aboriginal people and Tasmanian tigers traced to grave-robbing Victorian naturalist
1,000-year-old skeleton of noblewoman with hollowed-out skull found buried next to 'husband' in Germany
Strange 'blob' circling Milky Way's central black hole is shooting powerful radiation at Earth every 76 minutes