Low-grade inflammation and insulin resistance independently explain substantial parts of the association between body fat and serum C3: The CODAM study

作者：Wlazlo Nick^*; van Greevenbroek Marleen M J; Ferreira Isabel; Jansen Eugene J H M; Feskens Edith J M; van der Kallen Carla J H; Schalkwijk Casper G; Bravenboer Bert; Stehouwer Coen D A

来源：Metabolism-Clinical and Experimental, 2012, 61(12): 1787-1796.

DOI：10.1016/j.metabol.2012.05.015

• Complement C3
• Adiposity
• Body fat
• Insulin resistance
• Inflammation

Objective. To investigate the role of low-grade inflammation and insulin resistance (HOMA2-IR) in adiposity-related increases in serum complement factor 3 (C3). Although C3 has been linked to type 2 diabetes and cardiovascular diseases, and C3 levels are closely related to body fat, the underlying mechanisms explaining this association are still unknown. %26lt;br%26gt;Methods. Adiposity measures (including BMI, waist circumference (WC), sagittal diameter and several skinfolds), HOmA2-IR and markers of inflammation (hs-CRP, IL-6, SAA, haptoglobin, ceruloplasmin, sICAM-1) were determined in 532 individuals (62% men, mean age 59 +/- 6.9 yrs) from the Cohort on Diabetes and Atherosclerosis Maastricht study. Markers of inflammation were standardized and compiled into an averaged inflammation score. Cross-sectional associations between adiposity measures and C3 and the mediating role of low-grade inflammation and/or HOMA2-IR herein were analysed with multiple linear regression models. %26lt;br%26gt;Results. Adiposity measurements were significantly associated with C3 levels, with the strongest (adjusted) associations found for WC (beta =0.383; 95%CI 0.302-0.464) and sagittal diameter (beta =0.412; 95%CI 0.333-0.490). Further adjustment for inflammation and HOMA2-IR attenuated these associations to beta=0.115 (95%CI 0.030-0.200) and beta =0.163 (95%CI 0.082-0.244) respectively. Multiple mediation analyses showed that inflammation [beta=0.090 (95%CI0.060-0.126)] and HOMA2-IR beta=0.179 (95%CI 0.128-0.236)] each explained, independently of one another, a significant portion of the association between WC and C3 (23% and 47%, respectively). Similar mediation by inflammation (19-27%) and HOMA2-IR (37-56%) was found for other adiposity measures. %26lt;br%26gt;Conclusion. Systemic low-grade inflammation and insulin resistance may represent two independent pathways by which body fat leads to elevated C3 levels.

• 出版日期2012-12