Relationship of glycemic control, exogenous insulin, and C-peptide levels to ischemic heart disease mortality over a 16-year period in people with older-onset diabetes: the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR)

Diabetes Care. 2008 Mar;31(3):493-7. doi: 10.2337/dc07-1161. Epub 2007 Nov 19.


Objective: The purpose of this study was to examine the relationship of glycemic control and exogenous and endogenous insulin levels with all-cause and cause-specific mortality (ischemic heart disease and stroke) in an older-onset diabetic population.

Research design and methods: The Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) is an ongoing, prospective, population-based cohort study of individuals with diabetes first examined in 1980-1982. A stratified sample of all individuals with diabetes diagnosed at 30 years of age or older was labeled "older-onset" (n = 1,370). Those participating in the 1984-1986 examination phase (n = 1,007) were included in the analysis. Endogenous insulin was determined by measurements of plasma C-peptide (in nanomoles per liter), and exogenous insulin was calculated in units per kilogram per day. Glycemic control was determined by levels of glycosylated hemoglobin (HbA(1)).

Results: After 16 years of follow-up, 824 individuals died (all-cause mortality); 358 deaths involved ischemic heart disease and 137 involved stroke. C-peptide and HbA(1) were significantly associated with all-cause and ischemic heart disease mortality in our study. The hazard ratio (95% CI) values for all-cause mortality were 1.12 (1.07-1.17) per 1% increase in HbA(1), 1.20 (0.85-1.69) per 1 unit x kg(-1) x day(-1) increase in exogenous insulin, and 1.15 (1.04-1.29) per 1 nmol/l increase in C-peptide and for ischemic heart disease mortality were 1.14 (1.06-1.22), 1.50 (0.92-2.46), and 1.19 (1.02-1.39) for HbA(1), exogenous insulin, and C-peptide, respectively, after adjusting for relevant confounders. C-peptide was associated with stroke mortality only among men (1.65 [1.07-2.53]).

Conclusions: Our results show that individuals with higher endogenous insulin levels are at higher risk of all-cause, ischemic heart disease, and stroke mortality.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • C-Peptide / blood*
  • Cohort Studies
  • Diabetes Mellitus / blood*
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / epidemiology
  • Diabetic Retinopathy / blood
  • Diabetic Retinopathy / epidemiology
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / therapeutic use*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myocardial Ischemia / epidemiology
  • Myocardial Ischemia / mortality*
  • Prospective Studies
  • Survival Rate
  • Wisconsin / epidemiology


  • C-Peptide
  • Hypoglycemic Agents
  • Insulin