Key result
Higher C-peptide linked to ~19% higher ischemic heart disease mortality per 1 nmol/l.
Cohort (n=1,007)
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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.
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Hirai et al. (2008) conducted a cohort in Older-onset diabetes (diagnosed at ≥30 years of age) (n=1,007). Plasma C-peptide, HbA1, and exogenous insulin levels vs. Per 1 nmol/l increase in C-peptide, 1% increase in HbA1, and 1 unit/kg/day increase in exogenous insulin was evaluated on Ischemic heart disease mortality (per 1 nmol/l increase in C-peptide) (HR 1.19, 95% CI 1.02-1.39). Higher C-peptide and HbA1 levels were associated with increased ischemic heart disease mortality over 16 years (HR 1.19, 95% CI 1.02-1.39 per 1 nmol/l; HR 1.14, 95% CI 1.06-1.22 per 1%).
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