title: Fasting serum C-peptide levels predict cardiovascular and overall death in nondiabetic adults.
abstract: BACKGROUND
  Insulin resistance, characterized by hyperinsulinemia and normal or elevated serum glucose, is an established precursor to diabetes and cardiovascular disease. Despite fasting serum C-peptide levels being an accurate and stable marker of endogenous insulin production used in patients with diabetes, it is unknown whether C-peptide could serve as a marker of insulin resistance and predict outcomes in patients without diabetes.
  
  
  RESULTS
  This is a retrospective cohort study using data from the NHANES-3 (1988-1994) survey with mortality follow-up through December 31, 2006. Participants included 5153 subjects, 40 to 74 years of age with fasting glucose ≥ 70 mg/dL, without diabetes by history or laboratory testing. Receiver-operating-curve analysis compared fasting C-peptide against known insulin resistance measures such as fasting plasma glucose, serum insulin, HOMA-IR, quantitative-insulin-sensitivity-check-index, and metabolic syndrome for the prediction of cardiovascular and overall death. Subjects were then stratified by quartiles of C-peptide levels. Cox proportional-hazards modeling compared hazards of cardiovascular and overall death amongst C-peptide quartiles and adjusted for potential confounders of cardiovascular and diabetes risk. Fasting serum C-peptide levels predicted cardiovascular and overall death better than other studied measures (AUC=0.62 and 0.60 respectively vs the rest, with AUC ≤ 0.58 and ≤ 0.57 respectively, P<0.001). When compared with the lowest C-peptide quartile, subjects in the highest quartile had significantly higher adjusted hazard ratios (HR) of cardiovascular death (HR=1.60, 95%CI 1.07 to 2.39) and overall mortality (HR=1.72, 95%CI 1.34 to 2.21) after controlling for confounders.
  
  
  CONCLUSIONS
  C-peptide levels significantly related to hazards of cardiovascular and overall death in nondiabetic adults and was a better predictor of these outcomes than serum insulin and/or glucose derived measures.
authors: Research Enhancement Award Program, Providence Veterans Affairs Medical Center, Providence, RI 02908, USA.
authors: Nileshkumar
authors: N
authors: Patel
authors: Tracey H
authors: TH
authors: Taveira
authors: Gaurav
authors: G
authors: Choudhary
authors: Hilary
authors: H
authors: Whitlatch
authors: Wen-Chih
authors: WC
authors: Wu
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose; D002096:C-Peptide / Q000097:blood*; D002318:Cardiovascular Diseases / Q000401:mortality*; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000097:blood; D005215:Fasting; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009749:Nutrition Surveys; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin
keywords: cardiovascular risk; glucose intolerance; insulin resistance