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The Relationship of Glycemic Control, Exogenous Insulin, and C-peptide Levels to Ischemic Heart Disease Mortality Over a 16-year period in Persons with Older-Onset Diabetes: Wisconsin Epidemiologic Study of Diabetic Retinopathy

¹ Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
² Ophthalmology Federal University of Sao Paulo, Brazil

kleinr{at}epi.ophth.wisc.edu

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 is an ongoing prospective population-based cohort study of individuals with diabetes first examined in 1980-82. A stratified sample of all individuals with diabetes diagnosed at 30 years of age or older were labeled "older-onset" (n=1370). Those participating in the 1984-86 examination phase (n=1007) were included in the analysis. Endogenous insulin was determined by measurements of plasma c-peptide (nmol/l) and exogenous insulin was calculated in units/kg/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. Hazard ratios (95% CI) 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/day increase in exogenous insulin, and 1.15 (1.04-1.29) per 1 nmol/l increase in c-peptide. For ischemic heart disease mortality: 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.

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