UCSF Study Reveals Fat Tissue Fibrosis Drives Hidden Diabetes Risk in Non-Obese HIV Patients
核心洞察
A UCSF study found that people with well-controlled HIV (搜索) have more fibrosis in their fat tissues, which is associated with insulin resistance — a key predictor of type 2 diabetes (搜索).
The findings were consistent regardless of body weight or HIV (搜索) medication type, revealing that diabetes risk may not be apparent from body weight alone.
Researchers identified endotrophin (搜索), a blood marker of scarred fat, which could eventually help identify patients at highest risk for metabolic complications.
A new study from UC San Francisco has uncovered a mechanism that helps explain why people living with HIV (搜索) remain at elevated risk for type 2 diabetes (搜索), even when the virus is effectively suppressed with modern antiretroviral medications. The research, published online in JCI Insight on June 30, reveals that fat tissue fibrosis — scarring in adipose tissue — is strongly associated with insulin resistance in HIV patients, independent of body weight or specific drug regimens.
The study compared blood samples and fat biopsies from 46 people living with well-controlled HIV (搜索) to those from 74 people without HIV. None of the participants were obese or had diabetes at the time of assessment.
Fat Fibrosis Emerges as a Key Culprit
The researchers found that people with HIV (搜索) had significantly more fibrosis in their fat tissues, and this scarring was associated with insulin resistance — a critical predictor of type 2 diabetes (搜索). Notably, this fibrosis was evident in HIV patients regardless of their body weight or the particular types of HIV medications they were taking.
"In a few decades, we've turned HIV (搜索) 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. "These findings get us closer to preventing the unique and emerging metabolic health problems of this growing population."
Molecular Pathways Differ from Obesity-Related Fibrosis
To understand the origins of the fat fibrosis, the research team examined gene expression in the fat biopsies. They observed that genes involved in remodeling the extracellular matrix — the supportive material surrounding fat cells — and genes associated with an immune response were more active in HIV (搜索) patients. Conversely, pathways that control insulin signaling and lipid metabolism were less active.
These molecular changes were distinct from those seen in obesity-associated fibrosis, suggesting a unique pathophysiology underlying metabolic risk in the HIV (搜索) population.
Endotrophin (搜索): A Potential Blood-Based Biomarker
The study also discovered that both fat fibrosis and insulin resistance in people with HIV (搜索) were reflected by higher blood levels of a protein called endotrophin (搜索). This finding raises the possibility that a simple blood test could one day help clinicians identify patients at highest risk for developing diabetes.
"We think that fat fibrosis, detectable via endotrophin (搜索), could someday give us a lens into predicting the metabolic future of people living with HIV (搜索)," said Diana Alba, MD, an assistant professor of Medicine in the Division of Endocrinology at UCSF and first author of the study.
Limitations and Future Directions
Because the researchers measured participants only once, they could not determine whether scarring of fat directly leads to insulin resistance or diabetes. However, the findings represent an important first step toward understanding and eventually treating diabetes in the context of HIV (搜索), according to Koliwad. The research also suggests that diabetes risk in people with HIV may not always be apparent from body weight alone, underscoring the need for more nuanced screening approaches in this population.