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More Than 25% in HIV-Positive SUN Study Cohort Have Insulin Resistance
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6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 17-20, 2011, Rome
Mark Mascolini
Slightly more than one quarter of HIV-positive participants in the US SUN Study have insulin resistance, according to a 646-person analysis [1]. Current low-dose ritonavir raised the risk of insulin resistance 65% in this largely male study group.
US researchers designed the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) to analyze risk factors for antiretroviral-related complications in the context of longer survival in a prospective cohort. This analysis, however, is cross-sectional and reports cohort baseline insulin resistance. SUN cohort members come from 7 HIV clinics in St. Louis, Missouri, Providence, Rhode Island, Minneapolis, Minnesota, and Denver, Colorado. Cohort members are at least 18 years old and either antiretroviral naive with a CD4 count between 100 and 500 or antiretroviral experienced with a CD4 count above 100.
In this study SUN investigators used the homeostasis model assessment of insulin resistance (HOMA-IR) method (fasting glucose x fasting insulin), defining insulin resistance a HOMA-IR above 3. The study group included 646 people, 492 of them (76%) men. While 57% of cohort members were white, 30% were African American and 10% Hispanic.
The study group's age averaged 40.9 years and body mass index 26.5 kg/m(2). Only 10% of cohort members ever smoked, 13% had chronic hepatitis C virus (HCV) infection, and 6% had hepatitis B virus (HBV) infection. Insulin averaged 12.2 mcU/dL and glucose 94.5 mg/dL. Median HOMA-IR stood at 1.97 (interquartile range [IQR] 1.17 to 3.23). Total cholesterol averaged 185 mg/dL, low-density lipoprotein cholesterol 108 mg/dL, high-density lipoprotein (HDL) cholesterol 45 mg/dL, and triglycerides 172 mg/dL.
Median nadir CD4 count was 203 (IQR 87 to 313) and current CD4 count 468 (IQR 333 to 681). Most cohort members (79%) were taking antiretrovirals, and most (78%) had a viral load under 400 copies. Equivalent proportions were taking a protease inhibitor (36%) or a nonnucleoside (39%). More people were taking tenofovir (38%) than abacavir (21%).
The SUN team determined that 181 cohort members (28%) had insulin resistance on their first measure. (The study did not indicate whether or how much insulin resistance rates changed over time.) A multivariate model identified seven predictors of initial insulin resistance, at the following adjusted odds ratios (OR) (and 95% confidence intervals):
--Body mass index above 25 kg/m(2): OR 4.50 (2.89 to 7.00), P < 0.001
--HCV infection: OR 2.59 (1.50 to 4.48), P = 0.001
--Black (non-Hispanic) race: OR 2.25 (1.46 to 3.48), P < 0.001
--Systolic blood pressure over 140 mm Hg: OR 2.12 (1.21 to 3.71), P = 0.009
--Triglycerides at or above 150 mg/dL: OR 1.87 (1.22 to 2.88), P = 0.004
--Current ritonavir: OR 1.65 (1.07 to 2.53), P = 0.022
--HDL cholesterol below 40 mg/dL: OR 1.47 (0.98 to 2.21), P = 0.064 (not significant)
The SUN team believes "screening for insulin resistance should be a priority among aging adults chronically infected with HIV to prevent progression to diabetes mellitus and other co-morbidities."
A 137-person prospective study at two centers in Spain found an initial prevalence of insulin resistance in antiretroviral-naive people about half that in the SUN study's largely antiretroviral-experienced group: 12.4% [2]. The Spanish study also used HOMA-IR to determine insulin resistance but had a higher (stricter) cutoff of 3.8. In an analysis that excluded people with pretreatment insulin resistance, after 48 weeks of combination antiretroviral therapy, insulin resistance developed in 15 people, for an incidence of 13%. In this 2006 study, exposure to indinavir and HCV coinfection independently raised the risk of insulin resistance.
In a 1999-2003 prospective study of 533 men with HIV and 755 without HIV, Multicenter AIDS Cohort Study (MACS) investigators determined that cumulative exposure to nucleosides (but not nonnucleosides or protease inhibitors) independently raised the risk of insulin resistance measured by the QUICKI index [3]. A 2011 comparison of 322 MACS men with HIV and 534 without HIV found a significantly higher (worse) HOMA-IR score in the HIV group, which had a doubled risk of diabetes mellitus compared with the HIV-negative group (OR 1.98, 95% confidence interval 1.04 to 3.78) [4].
A 2009 cross-sectional comparison of 3227 HIV-positive men and 3240 HIV-negative men in the Veterans Aging Cohort Study found that HIV infection itself did not raise the risk of diabetes [5]. But three traditional diabetes risk factors--older age, HCV coinfection, and higher body mass index--had a stronger impact on diabetes risk in the HIV group.
References
1. Overton ET, Grubb JR, Baker J, et al. Prevalence and risk factors for insulin resistance in Study to Understand the Natural History of HIV (SUN study) cohort. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 17-20, 2011. Rome. Abstract TUPE132.
2. Palacios R, Merchante N, Macias J, et al. Incidence of and risk factors for insulin resistance in treatment-naive HIV-infected patients 48 weeks after starting highly active antiretroviral therapy. Antivir Ther. 2006;11:529-535.
3. Brown TT, Li X, Cole SR, et al. Cumulative exposure to nucleoside analogue reverse transcriptase inhibitors is associated with insulin resistance markers in the Multicenter AIDS Cohort Study. AIDS. 2005;19:1375-1383. http://pdfs.journals.lww.com/aidsonline/2005/09020/Cumulative_exposure_to_nucleoside_analogue_reverse.5.pdf.
4. Monroe AK, Dobs AS, Xu X, Palella FJ, Kingsley LA, Witt MD, Brown TT. Sex hormones, insulin resistance, and diabetes mellitus among men with or at risk for HIV infection. J Acquir Immune Defic Syndr. 2011. June 23. Epub ahead of print.
5. Butt AA, McGinnis K, Rodriguez-Barradas MC, et al; Veterans Aging Cohort Study. HIV infection and the risk of diabetes mellitus. AIDS. 2009;23:1227-1234.
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