Elevated Properdin and Enhanced Complement Activation in First-Degree Relatives of South Asian Subjects With Type 2 Diabetes

OBJECTIVE Emerging data implicate activation of the complement cascade in the pathogenesis of type 2 diabetes. The objective of the current study was to evaluate the relationships between components of the complement system, metabolic risk factors, and family history of type 2 diabetes in healthy South Asians. RESEARCH DESIGN AND METHODS We recruited 119 healthy, first-degree relatives of South Asian subjects with type 2 diabetes (SARs) and 119 age- and sex-matched, healthy South Asian control subjects (SACs). Fasting blood samples were taken for measurement of complement factors and standard metabolic risk factors. RESULTS SARs were characterized by significantly higher properdin (mean concentration 12.6 [95% CI 12.2-13.1] mg/L vs. SACs 10.1 [9.7-10.5] mg/L, P < 0.0001), factor B (187.4 [180.1-195.0] mg/L vs. SACs 165.0 [158.0-172.2] mg/L, P < 0.0001), and SC5b-9 (92.0 [86.1-98.3] ng/mL vs. SACs 75.3 [71.9-78.9] ng/mL, P < 0.0001) and increased homeostasis model assessment of insulin resistance (2.86 [2.61-3.13] vs. SACs 2.31 [2.05-2.61], P = 0.007). C-reactive protein did not differ between SARs and SACs (P = 0.17). In subgroup analysis of 25 SARs and 25 SACs with normal oral glucose tolerance tests, properdin, factor B, and SC5b-9 remained significantly elevated in SARs. CONCLUSIONS Increased properdin and complement activation are associated with a family history of type 2 diabetes in South Asians independent of insulin resistance, and predate the development of impaired fasting glucose and impaired glucose tolerance. Properdin and SC5b-9 may be novel biomarkers for future risk of type 2 diabetes in this high-risk population and warrant further investigation.