Department of Internal Medicine, Catharina Hospital, Eindhoven, the NetherlandsCARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the NetherlandsDepartment of Internal Medicine/Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands
CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the NetherlandsDepartment of Internal Medicine/Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.
Diabetes Care. 2014 Jul;37(7):1900-9. doi: 10.2337/dc13-2804. Epub 2014 Apr 23.
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.
免疫失调可影响胰岛素抵抗（IR）和β细胞功能，从而促成 2 型糖尿病（T2DM）的发生。补体系统作为免疫和炎症内稳的调节剂，可能是其中的一个相关因素。然而，针对补体作为 T2DM 和 IR 决定因素的纵向研究还很少。因此，我们前瞻性地研究了血浆补体因子 3（C3）与肌肉、肝脏和脂肪细胞中（IR 的估计值）的关系，以及与葡萄糖耐量的关系，包括 T2DM 的发生。
在一项前瞻性队列研究中，在基线时（n = 545）和 7 年随访后（n = 394）测量空腹 C3、非酯化脂肪酸、血糖和胰岛素（后者在口服葡萄糖耐量试验时测量）。
在 7 年期间，C3 水平（每 0.1 g/L）与更高的稳态模型评估的 IR（HOMA2-IR；β = 15.2%[95%CI 12.9-17.6]）、肝 IR（β = 6.1%[95%CI 4.7-7.4]）、脂肪细胞 IR（β = 16.0%[95%CI 13.0-19.1]）、空腹血糖（β = 1.8%[95%CI 1.2-2.4]）、2 小时血糖（β = 5.2%[95%CI 3.7-6.7]）和血糖曲线下面积（β = 3.6%[95%CI 2.7-4.6]）呈纵向相关。此外，C3（每 0.1 g/L）的变化与 HOMA2-IR（β = 0.08[95%CI 0.02-0.15]）和肝 IR（β = 0.87[95%CI 0.12-1.61]）的变化呈正相关，而与葡萄糖耐量无关。此外，基线 C3 与 T2DM 7 年发生率相关（比值比 1.5[95%CI 1.1-2.0]）。
C3 的变化与 IR 的多个指标的变化相关，可能反映了代谢失调的进展，最终导致葡萄糖耐量异常和 T2DM。
