A new study published in JCI Insight from Suneil Koliwad MD PhD and his team helps explain why non-obese people with HIV remain at elevated risk for type 2 diabetes despite effective suppression of the virus with modern medications. It marks the collective spirit of Diabetes Center, with members of Anderson, Parent, and Valdearcos labs included in the paper.
When comparing blood samples and fat biopsies of 46 people living with well-controlled HIV to those of 74 people without HIV, none of whom were obese or had diabetes, they found that the people with HIV had more fibrosis, or scarring, in their fat tissues, and this was associated with insulin resistance, a key predictor of type 2 diabetes.
The scarring was obvious in HIV patients no matter their body weight or the specific kinds of HIV medications they were taking. They also discovered a blood marker of the scarred fat, the protein endotrophin, which might eventually help identify the highest-risk patients. It suggests that diabetes risk in people with HIV may not always be apparent from body weight alone.
To understand the origins of fat scarring in HIV, the researchers looked into gene expression in fat biopsies. They saw that genes that control the tissue around fat cells as well as genes involved in inflammation were more active, changes that jibed with scarring. On the other hand, pathways that control insulin signaling and fat metabolism were less active. These pathways are often disrupted in diabetes.
The molecular changes in HIV-associated scarring were distinct from the changes known in obesity-associated scarring.
The researchers then found that both fat scarring and insulin resistance in people with HIV were reflected by higher blood levels of endotrophin.
Because the researchers measured participants only once, they couldn’t determine whether scarring of fat directly leads to insulin resistance or diabetes. But the findings are an important first step toward understanding and eventually treating diabetes in the context of HIV, according to Koliwad.
The finding puts us closer in touch with UCSF Center for AIDS Research (CFAR), as we approach broad collaboration positively. “We think that fat fibrosis, detectable via endotrophin, could someday give us a lens into predicting the metabolic future of people living with HIV,” said the paper's first author Diana Alba MD, Diabetes Center alum and now Assistant Professor of Medicine in Endocrinology.