C3 levels tied to incident T2DM; BMI plays a mediating role

Complement C3 levels may be used as a predictor of incident type 2 diabetes mellitus (T2DM), suggests a study. In addition, body mass index (BMI) may have a mediating role in the association between C3 and T2DM, offering clues for diabetes pathogenesis.

A group of researchers conducted a 10-year follow-up study to assess the relationship between C3 levels and incident T2DM, and further explore the potential role of BMI in such association. They determined serum C3 levels in 2,662 nondiabetic middle-aged and older individuals (mean age 64.62 years) from the Dongfeng‒Tongji cohort at baseline.

During 10 years of follow-up, the association between T2DM incidence and C3 levels was assessed using Cox regression. Mediation analysis was also conducted to examine the potential effect of BMI on the C3‒T2DM associations.

A total of 711 (26.7 percent) participants developed T2DM during 23,067 person-years of follow-up. After full adjustment, higher serum C3 significantly correlated with increased risk of incident T2DM (hazard ratio [HR], 1.16, 95 percent confidence interval [CI], 1.05‒1.27). Moreover, the HR in the fourth vs first quartile of C3 levels was 1.52 (95 percent CI, 1.14‒2.02; p_trend=0.029).

C3 levels also exhibited a robust and significant linear dose-responsive association with BMI (p_overall<0.001; p_nonlinear=0.96). On mediation analyses, BMI appeared to mediate 41.0 percent of the relationship between C3 levels and incident T2DM.

“Impairment of immune and inflammatory homeostasis is reported to be one of the causal factors of diabetes,” the researchers said.