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

• Published in: Diabetes care Vol. 35; no. 4; pp. 894 - 899
• Main Authors: Somani, Riyaz, Richardson, Victoria R, Standeven, Kristina F, Grant, Peter J, Carter, Angela M
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.04.2012
• Subjects: Adult; analysis; Asia, Southeastern - epidemiology; Asian Continental Ancestry Group - statistics & numerical data; Asian People; Asians; Biological and medical sciences; biomarkers; Biomarkers - analysis; Biomarkers - metabolism; blood; C-reactive protein; Cardiovascular disease; Case-Control Studies; complement; Complement Activation; Complement Activation - physiology; Complement Membrane Attack Complex; Complement Membrane Attack Complex - analysis; Complement Membrane Attack Complex - metabolism; Diabetes; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - immunology; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; epidemiology; ethnology; etiology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Family; Family Health; Family medical history; fasting; Female; glucose; glucose tolerance; Health aspects; Heart attacks; homeostasis; Humans; immunology; Insulin; Insulin resistance; Male; Medical sciences; Metabolic diseases; Metabolic Syndrome; Metabolic Syndrome - epidemiology; Metabolic Syndrome - ethnology; Metabolic Syndrome - etiology; Metabolic Syndrome - immunology; metabolism; Miscellaneous; noninsulin-dependent diabetes mellitus; Original Research; pathogenesis; physiology; Plasma; Properdin; Properdin - analysis; Properdin - metabolism; Public health. Hygiene; Public health. Hygiene-occupational medicine; risk; Risk Factors; Severe acute respiratory syndrome; Southeast Asia; statistics & numerical data; Studies; Teaching hospitals; Type 2 diabetes; Up-Regulation; Asia; South Asia; Southeast Asia; Endocrinopathy; Type 2 diabetes; Human; Immunomodulator; Nutrition; Properdin; Metabolic diseases; Activation; Complement; Inheritance(genetics); Endocrinology
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc11-1483

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.