Complement and Cardiometabolic Risk in Adolescents

Abstract

Background: Adipocytes produce complement C3 and respond to activation products of the complement cascade. Increased complement levels in adults predict future cardiometabolic disease such as type 2 diabetes and myocardial infarction. Since these diseases have their origins in childhood we studied the relationships of complement components, C3 and C4, to cardiometabolic risk factors in healthy, nonHispanic white adolescents. Methods: C3 and C4 levels, endothelial function (reactive hyperemia (RH), venous occlusion plethysmography), arterial stiffness (augmentation index (AI), arterial tonometry), lipids, interleukin-6 (IL-6), c-reactive protein, plasminogen activator inhibitor 1 (PAI1) insulin sensitivity and secretion (oral glucose tolerance test) were measured in 59 subjects (29 female, age=15.3±1.7 years, BMI=22.4.1±5.9 kg/m2, mean±SD). BMI percentile, waist circumference and percent body fat (air displacement) were measured to assess adiposity. Results: C3 correlated with multiple cardiometabolic risk factors including reactive hyperemia (r=0.41, p=0.002), LDL (r=0.34 p=0.012), triglycerides (r=0.56, p<0.001), PAI1 (r=0.30, p=0.023) insulin sensitivity (r=-0.31, p=0.024). C3 tended to correlated with AIX (r=0.25, p=0.074) and insulin secretion (r=0.24, p=0.079). C4 levels correlated with RH (r=0.28, p=0.043), AI (r=0.26, p=0.074) and IL-6 (r=0.41, p=0.003). Stepwise regression found that C3 levels predicted LDL independent of measures of adiposity and triglycerides in conjunction with waist circumference while C4 levels in conjunction with BMI%tile predicted AI, and IL-6 in conjunction with waist circumference. Adiposity measures alone predicted RH, HDL, PAI1 and insulin secretion and sensitivity. Conclusions: These results indicate that obesity induced increases in C3 are likely to play a significant role in the development of adverse lipids with increased plasma triglyceride and LDL levels while C4 plays a role in the development of increased arterial stiffness and inflammation. Disclosure R.P. Hoffman: None. M.M. Copenhaver: None. C. Yu: None.