1332-P: Complement C3 and C4 Levels Predict Cardiometabolic Risk in Healthy Adolescents

Complement, in addition to its immunologic functions, also helps regulate inflammation and fat metabolism. Thus, complement may play a role in the development of the metabolic syndrome. In adults complement component C3 is a risk factor for the development of type 2 diabetes, and a determinant of cardiometabolic risk. Adult cardiometabolic disease has its origins in childhood and adolescence. Therefore, if we are to fully understand the role of complement in cardiometabolic disease we need to study this age group. 56 healthy, non-Hispanic white adolescents (28 F, age 15.4±1.7 years; BMI 22.0±4.9 kg/m2 (mean±SD) were studied. Cardiometabolic risk factors were studied in the fasting state and included measures of vascular function [reactive hyperemia (RH), augmentation index (AI)], lipids, inflammation [white blood cell (WBC) and neutrophil (ANC) count, c-reactive protein (CRP), interleukin 6 (IL6)], carbohydrate metabolism [OGTT: insulin sensitivity (ISEN), insulin secretion (ISEC), disposition index, DI], endothelin 1 and plasminogen activator inhibitor 1 (PAI-1). RH worsened, HDL decreased and ANC, LDL, triglycerides and ISEC increased with increasing C3. RH and HDL were also negatively related to C4 while WBC, ANC, IL6 and DI were positively related to C4. Adjustment for body habitus eliminated the relationships of HDL, LDL and ISEC but not ANC or triglycerides to C3 and/or C4. Adjusted PAI-1 was significantly related to C3. Except for the positive relationship between C4 and DI these relationships demonstrate that increasing levels of C3 and C4 are associated with increasing cardiometabolic risk in healthy, non-Hispanic white adolescents. Increasing C3 levels may influence increasing triglyceride levels while increasing C4 is more closely related to increasing inflammation.