Genetic changes in diabetes are induced by obesity

Four functional genes with roles in insulin resistance have now been detected by an experimental epigenetic analysis of obesity. These study findings suggest that an epigenetic test could be created to identify those individuals early in the process of developing diabetes mellitus, providing hope for preventing the disease.

Andrew P. Feinberg, MD, and coworkers from Johns Hopkins University School of Medicine undertook a comparison of cells from mice that were overfed to mice that were lean to determine obesity-associated changes in epigenetic chemical tags on DNA. These chemical tags affect if and how much genes are used without actually changing the genetic code. 

Mice were fed either a normal diet or a high-calorie diet; mice on the high-calorie diet became obese and diabetic. Clear differences were observed between the obese and normal mice through analysis of epigenetic markers at more than 7 million sites in the DNA of their fat cells. Some sites with chemical tags called methyl groups were found in the lean mice but were missing in the obese mice, and vice versa. Methyl groups prevent genes from making proteins, which are needed for insulin secretion and proper metabolism. 

Researchers extended the analysis to humans, using adipose samples from lean and obese patients before and after gastric bypass surgery. The same pattern of differences was found.

As Feinberg comments, “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.” He adds, “It’s likely that when food supplies are highly variable, these epigenetic changes help our bodies adapt to temporary surges in calories. But if the high-calorie diet continues over the long term, the same epigenetic pattern raises the risk for disease.”

Some of the epigenetic changes associated with obesity affected genes known to elevate diabetes risk. Other epigenetic changes affected genes not definitively linked to diabetes, but connected to metabolism-how the body breaks down and uses nutrients. Further tests showed that some of these genes regulate insulin action on sugar uptake.

These research results point the way forward in diabetes research with regard to new potential drug targets for treating type 2 diabetes.