Synergistic association of high-sensitivity C-reactive protein and body mass index with insulin resistance in non-diabetic adults

Epidemiological evidence has indicated that inflammatory markers and obesity are strongly correlated with insulin resistance (IR). However, there is a paucity of studies assessing the complex interaction between elevated hs-CRP and body mass index (BMI), particularly among Asians. This study investigated the additive interaction between hs-CRP and BMI on IR, using cross-sectional data from the 7th Korea National Health and Nutrition Examination Survey (2016-2018). A total of 5706 men and 6707 women aged 20 years or older were evaluated, and a multiple logistic regression analysis was used to assess the association of serum hs-CRP and BMI with IR, as measured by the triglyceride-glucose index (TyG index). Sex-specific median values were used to dichotomise the continuous TyG index variable into insulin-sensitive and IR categories. Biological interaction was evaluated using the Relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI). The joint effects of high hs-CRP and overweight/obesity on IR were greater than would be expected from the effects of the individual exposures alone. Relative to those with low hs-CRP and BMI < 23, having both exposures was related to increased IR with an adjusted OR of 2.97 (95% CI 2.50-3.52) in men and 3.08 (95% CI 2.67-3.56) in women with significant additive interactions. These findings demonstrate that IR prevention strategies that reduce both systematic inflammation and BMI may exceed the expected benefits based on targeting these risk factors separately.