Clinical and cardiometabolic factors associated with insulin resistance in an adult population from a high HIV-burden setting in Zambia.
Liweleya Situmbeko S, Halubanza Brian B, Hanzooma Hatwiko H, Tembo Taonga T et al.
Insulin resistance (IR) is a key pathophysiological link between metabolic syndrome and type 2 diabetes. Among people living with HIV (PLWH), both antiretroviral therapy (ART) and chronic immune activation may potentiate IR. This study aimed to identify clinical and cardiometabolic correlates of IR. We conducted a cross-sectional study among 233 adults (142 PLWH and 91 people without HIV) attending routine medical checkups at Livingstone University Teaching Hospital, Zambia. Fasting glucose and insulin were used to calculate HOMA2-IR, with values >1.9 defining IR. Anthropometry, blood pressure, lipid parameters, hs-CRP, renal function, and echocardiographic measures were assessed. Multivariable logistic regression estimated adjusted odds ratios (aORs) and 95% confidence intervals, with HIV status retained a priori. Model selection emphasized parsimony, while multicollinearity was assessed using Spearman correlations and variance inflation factors (VIFs). Highly correlated predictors were not entered simultaneously. Model discrimination and calibration were assessed using the AUC and Hosmer-Lemeshow goodness-of-fit test, respectively. IR was present in 37 of 233 participants (15.9%). Compared with participants without IR, those with IR had higher BMI (28.4 vs. 24.45 kg/m2, p = 0.0002), waist circumference (99.7 vs. 82.5 cm, p < 0.0001), total cholesterol (4.87 vs. 4.31 mmol/L, p = 0.046), triglycerides (0.950 vs. 0.755 mmol/L, p = 0.0068), and VLDL cholesterol (0.400 vs. 0.300 mmol/L, p = 0.005), as well as higher hs-CRP concentrations (p = 0.0008). IVSD and LVPWD were also greater among participants with IR (p = 0.002 and p = 0.016, respectively). In the parsimonious multivariable model, waist circumference was independently associated with higher odds of IR (aOR 1.045 per cm; 95% CI: 1.012-1.080; p = 0.008), while HIV status, hypertension, triglycerides, and IVSD were not independently associated with IR. The model demonstrated moderate discrimination (AUC = 0.767; 95% CI: 0.676-0.858) with no evidence of significant lack of calibration (Hosmer-Lemeshow p = 0.164). IR was present in approximately one in six adults in this high HIV-burden setting and was characterized by greater adiposity, dyslipidemia, inflammation, and cardiac structural differences. After adjustment, WC was the only independent correlate of IR, while HIV status was not independently associated. These findings underscore the importance of incorporating adiposity and broader cardiometabolic assessment into routine care, including HIV care, and support prospective studies to clarify the temporal and mechanistic relationships between these factors.