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.

Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.