The role of C-reactive protein, adiponectin and leptin in the association between abdominal adiposity and insulin resistance in middle-aged individuals

Background and aims In the present study, we assessed the extent of mediation by low-grade systemic inflammation and adipokines in the association between abdominal adiposity and insulin resistance. Methods and results In this cross-sectional analysis of baseline measurements of the Netherlands Epidemiology of Obesity study, total body fat (TBF) was measured in all (n = 5772) participants who did not have missing data and neither used glucose-lowering medication, and abdominal subcutaneous adipose tissue (aSAT) and visceral adipose tissue (VAT) were assessed by MRI in a random subgroup (n = 2448). C-reactive protein (CRP), adiponectin, and leptin were considered as potential mediators, and insulin resistance was assessed by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Mediation by CRP, adiponectin, and leptin was studied by including the mediators to the fully adjusted linear regression model. Participants had a mean (SD) age of 56 (6) years, TBF of 36 (9) %, VAT of 119 (61) cm2 and aSAT of 300 (111) cm2. Per SD of TBF, VAT and aSAT, HOMA-IR was 64% (95% confidence interval [CI]: 59–70), 33% (95%CI: 28–42) and 20% (95%CI: 14–26) higher, respectively. The association between aSAT and HOMA-IR fully disappeared after adjustment for leptin; the association between VAT and HOMA-IR attenuated after adjustment for leptin (22%) and adiponectin (15%). No mediation was observed by CRP, and mediation estimates were similar in men and women. Conclusion Where leptin fully explained the aSAT-HOMA-IR association, the VAT-HOMA-IR association was only partly explained by leptin and adiponectin similarly in men and women.