C-peptide and the risk for incident complications and mortality in type 2 diabetic patients: a retrospective cohort study after a 14-year follow-up

Objective: C-peptide, a cleavage product of insulin, exerts biological effects in patients with type 1 diabetes mellitus, but its role in type 2 diabetes mellitus is controversial. Our aim was to examine the associations between fasting C-peptide levels and all-cause mortality, specific-cause mortality and the incidence of chronic complications in patients with type 2 diabetes. Design: Retrospective cohort study with a median follow-up of 14 years. Methods: A representative cohort of 2113 patients with type 2 diabetes mellitus and a subgroup of 931 individuals from this cohort without chronic complications at baseline from a diabetic clinic were studied. Results: Patients with higher C-peptide levels had higher baseline BMI and triglyceride and lower HDL-cholesterol values. During the follow-up, 46.1% of the patients died. In a Cox proportional hazard model, after multiple adjustments, no significant association was found between the C-peptide tertiles and all-cause mortality or mortality due to cancer, diabetes or cardiovascular diseases. In the subgroup of 931 patients without chronic complications at baseline, the incidence of microvascular complications decreased from the first to the third C-peptide level tertile, while the incidence of cardiovascular disease did not differ. The risks for incident retinopathy (hazard ratio (HR)=0.33; 95% confidence interval (CI) 0.23-0.47), nephropathy (HR=0.27; 95% CI 0.18-0.38) and neuropathy (HR=0.39; 95% CI 0.25-0.61) were negatively associated with the highest C-peptide tertile, after adjusting for multiple confounders. Conclusions: Higher baseline C-peptide levels were associated with a reduced risk of incident microvascular complications but imparted no survival benefit to patients with type 2 diabetes mellitus.