Comparison of Insulin Resistance to Coronary Atherosclerosis in Human Immunodeficiency Virus Infected and Uninfected Men (from the Multicenter AIDS Cohort Study)

Abstract

The relation between insulin resistance (IR) and coronary artery disease in patients with human immunodeficiency virus (HIV) infection remains incompletely defined. Fasting serum insulin and glucose measurements from 448 HIV-infected and 306 uninfected men enrolled in the Multicenter AIDS Cohort Study were collected at semiannual visits from 2003 to 2013 and used to compute the homeostatic model assessment of IR (HOMA-IR). Coronary computed tomographic angiography (CTA) was performed at the end of the study period to characterize coronary pathology. Associations between HOMA-IR (categorized into tertiles and assessed near the time of the CTA and over the 10-year study period) and the prevalence of coronary plaque or stenosis ≥50% were assessed with multivariate logistic regression. HOMA-IR was higher in HIV-infected men than HIV-uninfected men when measured near the time of CTA (3.2 vs 2.7, p = 0.002) and when averaged over the study period (3.4 vs 3.0, p <0.001). The prevalence of coronary stenosis ≥50% was similar between both groups (17% vs 15%, p = 0.41). Both measurements of HOMA-IR were associated with greater odds of coronary stenosis ≥50% in models comparing men with values in the highest versus the lowest tertiles, although the effect of mean HOMA-IR was stronger than the single measurement of HOMA-IR before CTA (odds ratio 2.46, 95% CI 1.95 to 3.11, vs odds ratio 1.43, 1.20 to 1.70). This effect was not significantly modified by HIV serostatus. In conclusion, IR over nearly a decade was greater in HIV-infected men than HIV-uninfected men, and in both groups, was associated with significant coronary artery stenosis.

Figure 1

The effect of HIV-infection on HOMA-IR tertile, presented as odds ratios relative to first, and lowest, tertile of HOMA-IR. Among 8,033 person-visits included in this analysis, 37% belonged to the first tertile, 32% to the second tertile, and 30% to the third tertile. Using a multivariable model, a graded association between HIV-infection and HOMA-IR measured near the time the CTA was performed was observed. HIV-infected men had 1.5 fold greater odds of having a HOMA-IR value in the second compared to the first tertile and 2.5 fold greater odds of having a HOMA-IR value in the third compared to the first tertile.

Figure 2

HOMA-IR (log transformed) in HIV-infected and HIV-uninfected men over the study interval. The solid lines represent the average change of log-transformed HOMA-IR over calendar time with the confidence interval estimated from the multivariate models, and dashed lines represent the same outcome estimated from the Loess fitting of raw data. Results from HIV-infected men include the red dashed and solid lines, while the blue dashed and solid lines represent uninfected men. There was no significant change in HOMA-IR levels among both HIV-infected and uninfected men, but HOMA-IR levels were higher among HIV-infected men than in uninfected men.