Why some obese people don’t develop diabetes

"This research demonstrates that some obese people are protected from the adverse metabolic effects of moderate weight gain, whereas others are predisposed to develop these problems," says senior investigator Samuel Klein. (Credit: Arti Sandhu/Flickr)

For some people, obesity does not come with metabolic changes that can lead to diabetes, heart disease, and stroke—even after they gain more weight.

To find out why, researchers studied 20 obese participants who were asked to gain about 15 pounds over several months to determine how the extra pounds affected their metabolic functions.

Listen to Samuel Klein discuss the findings:


“Our goal was to have research participants consume 1,000 extra calories every day until each gained 6 percent of his or her body weight,” says Elisa Fabbrini, an assistant professor at Washington University School of Medicine in St. Louis.

“This was not easy to do. It is just as difficult to get people to gain weight as it is to get them to lose weight,” adds Fabbrini, who is first author of a study published in the Journal of Clinical Investigation.

All of the subjects gained weight by eating at fast-food restaurants, under the supervision of a dietitian. The researchers chose fast-food chain restaurants that provide rigorously regulated portion sizes and nutritional information.

25% of obese people

Before and after weight gain, the researchers carefully evaluated each study subject’s body composition, insulin sensitivity, and ability to regulate blood sugar, liver fat, and other measures of metabolic health.

After gaining weight, the metabolic profiles of obese subjects remained normal if they were in the normal range when the study began. But the metabolic profiles significantly worsened after weight gain in obese subjects whose metabolic profiles already were abnormal when the study got under way.

“This research demonstrates that some obese people are protected from the adverse metabolic effects of moderate weight gain, whereas others are predisposed to develop these problems,” says senior investigator Samuel Klein, a professor of medicine and nutritional science and director of Washington University’s Center for Human Nutrition.

“This observation is important clinically because about 25 percent of obese people do not have metabolic complications,” he adds. “Our data shows that these people remain metabolically normal even after they gain additional weight.”

As part of the study, the researchers then helped the subjects lose the weight they had gained.

“It’s important to point out that once the study was completed, we enrolled all subjects in our weight-loss program to make sure they lost all of the weight they had gained, or more,” says Klein.

The key differences

“We need more studies to try to understand why obesity causes specific diseases in some people but not in others,” Klein says. “Could it be genetics, specific dietary intake, physical lifestyle, emotional health, or even the microbes that live in the gut?”


The researchers identified some key measurements that distinguished metabolically normal obese subjects from those with problems. One was the presence of fat inside the liver. Those with abnormal metabolism accumulated fat there.

Another difference involved gene function in fat tissue. People with normal metabolism in spite of their obesity expressed more genes that regulate fat production and accumulation.

And the activity of those genes increased even more when the metabolically normal people gained weight. That wasn’t true for people with abnormal metabolism.

“These results suggest that the ability of body fat to expand and increase in a healthy way may protect some people from the metabolic problems associated with obesity and weight gain,” notes Klein.

Klein and his colleagues plan to more closely analyze fat, muscle, and liver tissue and to include lean people in future studies so that the researchers can learn more about how and why some individuals are protected from metabolic problems while others are vulnerable.

The National Institute of Diabetes and Digestive and Kidney Diseases and the National Center for Research Resources of the National Institutes of Health, the Longer Life Foundation, and the Kilo Foundation funded the study.

Source: Washington University in St. Louis