The following is a summary of “Association of Complement C3 With Incident Type 2 Diabetes and the Mediating Role of BMI: A 10-Year Follow-Up Study,” published in the March 2023 issue of Endocrinology & Metabolism by Jiang, et al.

For a study, researchers sought to investigate the association between complement C3 levels and the incidence of type 2 diabetes mellitus (T2DM) and to explore the potential mediating role of body mass index (BMI) in the association.

The prospective study included 2,662 middle-aged and elderly (64.62 ± 7.25 years) nondiabetic individuals from the Dongfeng-Tongji cohort. The participants’ serum C3 levels were measured at baseline, and they were followed up for 10 years to monitor the incidence of T2DM. Cox regression analysis examined the relationship between C3 levels and T2DM incidence. In addition, mediation analysis was conducted to assess the mediating effect of BMI on the C3-T2DM association.

During the follow-up period, 711 (26.7%) participants developed T2DM. After adjusting for relevant covariates, a significant positive association was found between serum C3 levels and incident T2DM (HR [95% CI] = 1.16 [1.05, 1.27]; per SD higher). Moreover, the incidence of T2DM was significantly higher in the fourth quartile of C3 levels compared to the first quartile (HR [95% CI] = 1.52 [1.14, 2.02]; Ptrend = 0.029). There was also a significant linear dose-response relationship between C3 levels and BMI (Poverall < 0.001, Pnonlinear = 0.96). Furthermore, BMI was found to mediate 41.0% of the association between C3 and T2DM.

Complement C3 may be an early biomarker for incident T2DM, and BMI may mediate the association between C3 levels and T2DM incidence. These findings provide insights into the pathogenesis of T2DM and suggest that targeting complement C3 levels may be a promising approach to preventing or treat T2DM.