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 it, the team compared blood samples and fat biopsies from 46 people living with well-controlled HIV to those from 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. This fibrosis was obvious in HIV patients no matter their body weight or the specific kinds of HIV medications they were taking.
The research also discovered a blood marker of the scarred fat, which might eventually help identify the highest-risk patients. It also 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."
Suneil Koliwad, Chief of the Division of Endocrinology and Metabolism, UCSF Health
To understand the origins of the fat fibrosis, the researchers looked into gene expression in the fat biopsies. They saw that genes involved in remodeling the extracellular matrix - the supportive material surrounding fat cells - and an immune response were more active. On the other hand, pathways that control insulin signaling and lipid metabolism were less active.
These molecular changes were distinct from those seen in obesity-associated fibrosis.
The researchers also found that both fat fibrosis and insulin resistance in people with HIV were reflected by higher blood levels of a protein called 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.
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