Sex hormones, insulin resistance, and diabetes mellitus among men with or at risk for HIV infection
Monroe AK, Dobs AS, Xu X, Palella FJ, Kingsley LA, Witt MD, Brown TT. J Acquir Immune Defic Syndr. 2011 Jun 23. [Epub ahead of print]
The objective of this study was to examine the relationship of free testosterone and sex hormone-binding globulin with insulin resistance and diabetes mellitus in HIV disease. The design was a cross-sectional analysis of 322 HIV-uninfected and 534 HIV-infected men in the Multicenter AIDS Cohort Study. The main outcomes were diabetes mellitus and homeostasis model assessment (HOMA)-insulin resistance. Diabetes mellitus was defined as fasting serum glucose ≥ 126 or self-reported diabetes mellitus and use of diabetes mellitus medications. HOMA-insulin resistance was calculated from fasting serum glucose and fasting insulin. Compared with HIV-uninfected men in this sample, HIV-infected men were younger, with lower body mass index, and more often black. HIV-infected men had lower free testosterone (p < 0.001) and higher sex hormone-binding globulin (p < 0.0001). The adjusted odds ratio for diabetes mellitus was 1.98 (95% CI 1.04-3.78); mean adjusted log HOMA-insulin resistance was 0.21 units higher in HIV-infected men (p < 0.0001). Log sex hormone-binding globuline, but not log free testosterone, was associated with diabetes mellitus (OR = 0.44, 95% CI 0.25, 0.80) in both groups. Log free testosterone and log sex hormone-binding globuline were inversely related to insulin resistance (p < 0.05 for both), independent of HIV. Compared to HIV-uninfected men, HIV-infected men had lower free testosterone, higher sex hormone-binding globulin, and more insulin resistance and diabetes mellitus. Lower free testosterone and lower sex hormone-binding resistance were associated with insulin resistance regardless of HIV serostatus. This suggests that sex hormones play a role in the pathogenesis of glucose abnormalities among HIV-infected men.
Editor’s note: The higher sex hormone-binding globulin levels seen in men with HIV infection in this cross-sectional study should confer a protective effect against insulin resistance but the converse was seen: HIV-positive men were more insulin resistant and more likely to have diabetes mellitus than HIV-negative men. Hepatitis C infection was associated with insulin resistance in this study and ever having used the antiretroviral stavudine (d4T) was strongly associated with both insulin resistance and diabetes mellitus, as were lower levels of the sex hormone testosterone. The latter association is likely mediated by body fat, particularly visceral adipose tissue. Diabetes is a common problem among people living with HIV and preventing its development will reduce the risk of cardiovascular and kidney disease. Getting rid of central fat through lifestyle changes to promote weight loss would improve both insulin sensitivity and increase testosterone levels. What would be the down side of that?