The cross-sectional association between insulin resistance and circulating complement C3 is partly explained by plasma alanine aminotransferase, independent of central obesity and general inflammation (the CODAM study)
P>Background Complement C3, a central component of the innate immune system is increased in subjects with obesity and type 2 diabetes and is a novel risk factor for cardiovascular disease. We hypothesized that the strong association between insulin resistance and circulating amounts of C3 may be related to hepatic fat accumulation -independent of central obesity itself and of a general low-grade inflammatory response. Research question To what extent is the association between insulin resistance and C3 explained by plasma levels of alanine aminotransferase (ALT) as a surrogate of hepatic fat accumulation. Methods Cross-sectional analyses conducted in the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study. Analyses were restricted to subjects with none-to-moderate alcohol consumption (n = 453, 61 center dot 4% men). Multiple linear regression analyses were used to investigate the association between HOMA2IR (main determinant) and circulating complement C3 (main outcome), and the mediating role of ALT herein. All analyses were adjusted for age, sex, presence of type 2 diabetes mellitus or heart disease, use of medication, smoking, alcohol consumption, waist circumference and inflammation. Results Insulin resistance (estimated as HOMA2IR) was strongly associated with circulating C3 (standardized regression coefficient beta 0 center dot 40 [95% CI: 0 center dot 30; 0 center dot 49]) and also with ALT (beta 0 center dot 44 [0 center dot 34; 0 center dot 54]), both adjusted for the above-mentioned covariates. The association between HOMA2IR and C3 was attenuated after further adjustment for ALT (beta decreased to 0 center dot 34 [0 center dot 24; 0 center dot 44]). Concluding Remarks Plasma ALT can explain 14 center dot 2% of the strong association between insulin resistance and circulating concentrations of complement C3, independent of central obesity and general inflammation.
| Main Authors: | , , , , , , , , |
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| Format: | Article/Letter to editor biblioteca |
| Language: | English |
| Subjects: | component-3, endothelial-cells, fatty liver-disease, metabolic syndrome, myocardial-infarction, nonalcoholic steatohepatitis, population-based cohort, reactive protein, risk-factor, serum c3, |
| Online Access: | https://research.wur.nl/en/publications/the-cross-sectional-association-between-insulin-resistance-and-ci |
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