Sex differences in insulin resistance and associated metabolic and inflammatory markers among adults with and without HIV in Zambia

Insulin resistance (IR) contributes substantially to cardiovascular disease and type 2 diabetes mellitus, with increasing concern among people living with HIV (PLWH). However, sex‐specific factors of IR in sub‐Saharan Africa remain poorly understood. This study evaluated sex‐specific associations between IR and clinical, metabolic, and inflammatory markers among adults with and without HIV in Zambia. A cross‐sectional study was conducted among 233 adults in Zambia. Insulin resistance was assessed using the Homeostatic Model Assessment for Insulin Resistance (HOMA‐IR). Sex‐stratified multivariable linear regression models were used to identify factors associated with IR. Females had higher body mass index (26.9 vs. 23.5 kg/m 2 , p < 0.001), waist circumference (88.3 vs. 83.2 cm, p = 0.008), fasting insulin, and HOMA‐IR compared with males. In the adjusted overall model, female sex was associated with higher HOMA‐IR ( β = 0.95, 95% CI: 0.06–1.84; p = 0.037), while HIV‐positive status was associated with lower HOMA‐IR ( β = −1.54, 95% CI: −3.06 to −0.02; p = 0.046). Among males, hypertension was associated with higher HOMA‐IR ( β = 0.61; p = 0.019), whereas among females, HIV‐positive status was inversely associated with HOMA‐IR ( β = −2.31; p = 0.049). Insulin resistance highlighted sex‐specific patterns, with greater metabolic risk among females and distinct clinical factors among males. Future studies incorporating lifestyle and hormonal factors are needed to clarify these relationships.