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

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 and Stehouwer, Coen D. A. (2012) Low-grade inflammation and insulin resistance independently explain substantial parts of the association between body fat and serum C3: The CODAM study. Metabolism: Clinical and Experimental, 61 12: 1787-1796. doi:10.1016/j.metabol.2012.05.015


Author 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.
Title Low-grade inflammation and insulin resistance independently explain substantial parts of the association between body fat and serum C3: The CODAM study
Journal name Metabolism: Clinical and Experimental   Check publisher's open access policy
ISSN 0026-0495
Publication date 2012-01-01
Sub-type Article (original research)
DOI 10.1016/j.metabol.2012.05.015
Volume 61
Issue 12
Start page 1787
End page 1796
Total pages 10
Place of publication Maryland Heights, MO United States
Publisher W.B. Saunders
Language eng
Abstract 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. 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. Results: Adiposity measurements were significantly associated with C3 levels, with the strongest (adjusted) associations found for WC (β = 0.383; 95%CI 0.302-0.464) and sagittal diameter (β = 0.412; 95%CI 0.333-0.490). Further adjustment for inflammation and HOMA2-IR attenuated these associations to β = 0.115 (95%CI 0.030-0.200) and β = 0.163 (95%CI 0.082-0.244) respectively. Multiple mediation analyses showed that inflammation [β = 0.090 (95%CI 0.060-0.126)] and HOMA2-IR [β = 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. Conclusion: Systemic low-grade inflammation and insulin resistance may represent two independent pathways by which body fat leads to elevated C3 levels.
Keyword Adiposity
Body fat
Complement C3
Inflammation
Insulin resistance
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Public Health Publications
 
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Created: Thu, 21 May 2015, 01:34:22 EST by Isabel Ferreira on behalf of School of Public Health