Elsevier

Metabolism

Volume 61, Issue 12, December 2012, Pages 1787-1796
Metabolism

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

https://doi.org/10.1016/j.metabol.2012.05.015Get rights and content
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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.

Abbreviations

ALT
alanine aminotransferase
BMI
body mass index
C3
complement factor 3
CVD
cardiovascular disease
eGFR
estimated glomerular filtration rate
HC
hip circumference
HOMA2-IR
homeostasis model assessment insulin resistance
hs-CRP
high sensitivity C-reactive protein
IL-1
interleukin-1
IL-6
interleukin-6
IFN-γ
interferon-γ
TNF-α
tumour necrosis factor-α
SAA
serum amlyoid A
sICAM-1
soluble inter-cellular adhesion molecule-1
T2DM
type 2 diabetes mellitus
WC
waist circumference
WHR
waist-to-hip ratio

Keywords

Complement C3
Adiposity
Body fat
Insulin resistance
Inflammation

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