Drugs called thiazolidinediones (TZDs) reverse insulin resistance in patients with type 2 diabetes by targeting the activity of a receptor protein. However, an array of side effects including weight gain, edema, and high cholesterol, limits their use in the clinic.

In a new study published in Cell Stem Cell, a team of researchers led by Mitchell Lazar, director of the Institute for Diabetes, Obesity, and Metabolism in the Perelman School of Medicine, have demonstrated—using fat cells derived from human stem cells—that individual genetic variation can be used to predict whether the TZD rosiglitazone will produce the unwanted side effect of increasing cholesterol levels in certain individuals.

“Obesity has reached global epidemic proportions and is a major risk factor for type 2 diabetes, so any steps we can take toward understanding how patients respond to treatment is crucial,” Lazar says. “We found that genetic variation impacts how PPARγ [a receptor protein] interacts with the genome DNA in fat cells. This determines an individual's responses to anti-diabetic drugs and has direct implications for developing personalized therapies for diabetes.”