People living with well-controlled HIV face an elevated risk of developing type 2 diabetes due to increased scarring in their fat tissues, according to a University of California – San Francisco study published June 30 in JCI Insight.
Fat Fibrosis and Insulin Resistance in HIV
Researchers at UCSF investigated why patients with suppressed HIV maintain a higher vulnerability to metabolic complications. According to the study, the team compared blood samples and fat biopsies from 46 people living with well-controlled HIV against samples from 74 people without HIV. None of the participants in either group had obesity or diabetes.
The analysis revealed that participants with HIV had significantly more fibrosis, or scarring, in their fat tissues. This scarring directly correlated with insulin resistance, a primary predictor of type 2 diabetes. The presence of this fibrosis remained consistent regardless of the patients’ body weight or the specific HIV medications they were taking.
Did you know? In a few decades, medical advancements have transformed HIV from an often-tragic disease into a manageable, chronic condition, according to Dr. Suneil Koliwad, chief of the Division of Endocrinology and Metabolism at UCSF Health and senior author of the study. However, this success has brought new clinical challenges, including emerging metabolic health problems.
Molecular Changes in Adipose Tissue
To uncover the root causes of the tissue scarring, the study examined gene expression within the fat biopsies. Investigators observed that genes responsible for remodeling the extracellular matrix—the supportive material surrounding fat cells—along with immune response genes, showed higher activity levels. Conversely, molecular pathways that control insulin signaling and lipid metabolism were less active.
These specific molecular shifts differed from the patterns typically observed in obesity-associated tissue fibrosis. Because the researchers measured participants only once during the project, they could not definitively determine whether fat scarring directly triggers insulin resistance or subsequent diabetes. Even so, the findings establish an essential baseline for understanding and eventually treating metabolic dysfunction in patients with HIV, according to Dr. Koliwad.
Blood Marker Identifies High-Risk Patients
The research team also identified a potential screening tool in the blood. Higher blood levels of a protein called endotrophin accurately reflected both the presence of fat fibrosis and insulin resistance in study participants with HIV.
“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 Dr. Diana Alba, an assistant professor of medicine in the Division of Endocrinology at UCSF and first author of the study.
This blood marker could eventually help clinicians identify patients at the highest risk for type 2 diabetes before clinical symptoms appear. It also highlights the reality that metabolic risk in this population cannot always be assessed through body weight alone.
Frequently Asked Questions
Why are people with well-controlled HIV at higher risk for type 2 diabetes?
Research shows that individuals with HIV can develop increased scarring, or fibrosis, in their fat tissues. This scarring is associated with insulin resistance, a key predictor of type 2 diabetes, even when the virus is effectively suppressed by modern medications.
Does body weight determine diabetes risk in patients with HIV?
Not entirely. The UCSF study found that fat fibrosis and associated insulin resistance occurred in patients with HIV regardless of their body weight.
What is endotrophin?
Endotrophin is a protein found in the blood. Researchers discovered that higher levels of endotrophin serve as a blood marker for scarred fat tissue and insulin resistance in people living with HIV.
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