Serum C-peptide levels and risk of death among adults without diabetes mellitus.

BACKGROUND Connecting peptide (C-peptide) plays a role in early atherogenesis in patients with diabetes mellitus and may be a marker for cardiovascular morbidity and mortality in patients without diabetes. We investigated whether serum C-peptide levels are associated with all-cause, cardiovascular-related and coronary artery disease-related mortality in adults without diabetes. METHODS We used data from the Third Nutrition and Health Examination Survey (NHANES III) and the NHANES III Linked Mortality File in the United States. We analyzed mortality data for 5902 participants aged 40 years and older with no history of diabetes and who had available serum C-peptide levels from the baseline examination. We grouped the participants by C-peptide quartile, and we performed Cox proportional hazards regression analysis. The primary outcome was all-cause, cardiovascular-related and coronary artery disease-related mortality. RESULTS The mean serum C-peptide level in the study sample was 0.78 (± standard deviation 0.47) nmol/L. The adjusted hazards ratio comparing the highest quartile with the lowest quartile was 1.80 (95% confidence interval [CI] 1.33-2.43) for all-cause mortality, 3.20 (95% CI 2.07-4.93) for cardiovascular-related mortality, and 2.73 (95% CI 1.55-4.82) for coronary artery disease-related mortality. Higher C-peptide levels were associated with increased mortality among strata of glycated hemoglobin and fasting serum glucose. INTERPRETATION We found an association between serum C-peptide levels and all-cause and cause-specific mortality among adults without diabetes at baseline. Our finding suggests that elevated C-peptide levels may be a predictor of death.