Gender differences in the association of insulin resistance and high-sensitivity c-reactive protein in obese adolescents

Background: Low-grade vascular inflammation is believed to initiate early atherosclerotic process by inducing insulin resistance (IR), with significant gender differences in adults. We evaluated the relationship between surrogate measures of inflammation and IR in obese adolescents. Methods: The association among markers of inflammation [high-sensitivity c-reactive protein (hs-CRP)] and IR, cardiometabolic risk factors and body composition was retrospectively examined in 199 obese adolescents [(111 F/88 M), aged 15.5 +/- 1.2 years]. Insulin resistance was assessed using homeostatic model assessment for insulin resistance (HOMA-IR). Results: Males had higher body mass index SD-score (BMI-SDS), fat mass (FM), glucose, insulin, HOMA-IR, HbA(1c), hs-CRP, triglycerides: HDL-C (TG: HDL-C) ratio than females (p < 0.05), whereas females had higher c-peptide: insulin ratio than males (p < 0.05). Also, 50.8% of subjects were identified with metabolic syndrome with similar gender distribution (M: 57.9% vs. F: 45.1%, p = 0.32). Hs-CRP was correlated with HOMA-IR in the cohort, even when controlling for FM (r = 0.26; p < 0.0001). However, hs-CRP and HOMA-IR displayed a significant correlation only in females (r = 0.37; p < 0.0001) when adjusting for FM and pubertal status. Also, c-peptide: insulin ratio was inversely correlated with hs-CRP (r = -0.32; p < 0.001) and HOMA-IR (r = -0.62; p < 0.0001) and partially mediated the relationship between these biomarkers only among females (beta = 0.36, p < 0.001 to beta = 0.18, p < 0.05; Sobel Test: p < 0.01). Conclusions: A positive association between hs-CRP and HOMA-IR was observed only in adolescent girls which was influenced by altered hepatic insulin clearance. This implies that obese adolescent girls may be at greatest risk of developing early atherosclerosis and diabetes.