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

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Abstract
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 (HbA1). 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 HbA1 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 HbA1, 1.20 (0.85–1.69) per 1 unit · kg−1 · 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 HbA1, 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.