Complement Factor 3 Is Associated With Insulin Resistance and With Incident Type 2 Diabetes Over a 7-Year Follow-up Period: The CODAM Study

• Published in: Diabetes care Vol. 37; no. 7; pp. 1900 - 1909
• Main Authors: WLAZLO, Nick, VAN GREEVENBROEK, Marleen M. J, FERREIRA, Isabel, FESKENS, Edith J. M, VAN DER KALLEN, Carla J. H, SCHALKWIJK, Casper G, BRAVENBOER, Bert, STEHOUWER, Coen D. A
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.07.2014
• Subjects: Adipocytes - metabolism; Aged; Biological and medical sciences; Blood Glucose; Cohort Studies; Complement C3 - metabolism; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fasting; Fatty acids; Fatty Acids, Nonesterified - metabolism; Female; Follow-Up Studies; Glucose; Glucose Tolerance Test; Homeostasis; Humans; Insulin - blood; Insulin resistance; Insulin Resistance - physiology; Insulin-Secreting Cells - metabolism; Longitudinal Studies; Male; Medical sciences; Metabolic diseases; Middle Aged; Prospective Studies; Endocrinopathy; Type 2 diabetes; Human; Pancreatic hormone; Mishap; Nutrition; Metabolic diseases; Complement; Insulin; Target tissue resistance; Surveillance; Cause; Insulin resistance; Endocrinology
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc13-2804

Immune dysregulation can affect insulin resistance (IR) and β-cell function and hence contribute to development of type 2 diabetes mellitus (T2DM). The complement system, as a regulator of immune and inflammatory homeostasis, may be a relevant contributor therein. However, longitudinal studies focusing on complement as a determinant of T2DM and IR are scarce. Therefore, we prospectively investigated the association of plasma complement factor 3 (C3) with (estimates of) IR in muscle, liver, and adipocytes, as well as with glucose tolerance, including incident T2DM. Fasting C3, nonesterified fatty acids, glucose, and insulin (the latter two during oral glucose tolerance tests) were measured at baseline (n = 545) and after 7 years of follow-up (n = 394) in a prospective cohort study. Over the 7-year period, C3 levels (per 0.1 g/L) were longitudinally associated with higher homeostasis model assessment of IR (HOMA2-IR; β = 15.2% [95% CI 12.9-17.6]), hepatic IR (β = 6.1% [95% CI 4.7-7.4]), adipocyte IR (β = 16.0% [95% CI 13.0-19.1]), fasting glucose (β = 1.8% [95% CI 1.2-2.4]), 2-h glucose (β = 5.2% [95% CI 3.7-6.7]), and area under the curve for glucose (β = 3.6% [95% CI 2.7-4.6]). In addition, greater changes in C3 (per 0.1 g/L) were associated with greater changes in HOMA2-IR (β = 0.08 [95% CI 0.02-0.15]) and greater changes in hepatic IR (β = 0.87 [95% CI 0.12-1.61]) over 7 years, but not glucose tolerance. Moreover, baseline C3 was associated with the 7-year incidence of T2DM (odds ratio 1.5 [95% CI 1.1-2.0]). Changes in C3 were associated with changes in several measures of IR and may reflect progression of metabolic dysregulation, which eventually leads to abnormalities in glucose tolerance and T2DM.