Adults Living with HIV Are at High Risk for Diabetes. Here’s Why
UCSF study links scarred fat tissue to insulin resistance in people with HIV, even when they aren’t obese.
A new UC San Francisco study helps explain why people with HIV remain at elevated risk for type 2 diabetes despite effective suppression of the virus with modern medications.
To investigate, the team compared blood samples and fat biopsies of 46 people living with well-controlled HIV to those of 74 people without HIV. None of the participants were obese or had diabetes.
The researchers 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.
The researchers 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.
“In a few decades, we’ve turned HIV from an often-tragic disease into a manageable, chronic condition,” said Suneil Koliwad, MD, PhD, chief of the Division of Endocrinology and Metabolism at UCSF Health and senior author of the paper, which appeared online in JCI Insight on June 30. “These findings get us closer to preventing the unique and emerging metabolic health problems of this growing population.”
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.
“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 Diana Alba, MD, an assistant professor of Medicine in the Division of Endocrinology at UCSF and first author of the study.
Authors: UCSF authors are Alaa Abdellatif, MS; Moon K. Choi, MD; Stephen Brown Mayfield; Thuy An T. Pham; David Berrios; Antonio E. Rodriguez; Marin Ewing; Tony Figueroa; Judy Gonzalez-Vargas; Steven G. Deeks, MD; and Peter W. Hunt, PhD. For all authors see the paper.
Funding: National Institutes of Health (R01DK141041, R01DK112304, R56DK133997, K08DK124679, T32DK007418, P30DK098722, P30AI027763); Robert Wood Johnson Foundation.