Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Diabetes care, 2014-07, Vol.37 (7), p.1900-1909

Ort / Verlag

Alexandria, VA: American Diabetes Association

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.