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American Journal of Epidemiology Advance Access originally published online on May 25, 2007
American Journal of Epidemiology 2007 166(4):393-402; doi:10.1093/aje/kwm096
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American Journal of Epidemiology © The Author 2007. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

ORIGINAL CONTRIBUTIONS

Association between Glycosylated Hemoglobin Level and Cardiovascular and All-Cause Mortality in Type 1 Diabetes

Anoop Shankar1, Ronald Klein2, Barbara E. K. Klein2 and Scot E. Moss2

1 Department of Community, Occupational, and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
2 Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, WI

Correspondence to Dr. Anoop Shankar, Department of Community, Occupational, and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Block MD3, 16 Medical Drive, Singapore 117597 (e-mail: ashankar{at}nus.edu.sg).

Received for publication June 22, 2006. Accepted for publication February 22, 2007.

Hyperglycemia is implicated in the development and progression of microvascular complications in type 1 diabetes. In contrast, the association between hyperglycemia and macrovascular complications or mortality in type 1 diabetes is not clear. The authors studied a population-based cohort of 879 individuals with type 1 diabetes from Wisconsin, free of cardiovascular disease and end-stage renal disease at the baseline examination (1980–1982). The main outcome of interest was all-cause (n = 201) and cardiovascular (n = 132) mortality as of December 31, 2001. Elevated glycosylated hemoglobin levels were associated with all-cause and cardiovascular mortality, independent of duration of diabetes, smoking, hypertension, and proteinuria. The multivariable relative risks comparing the highest quartile of glycosylated hemoglobin (≥12.1%) with the lowest quartile (≤9.4%) were 2.42 (95% confidence interval: 1.54, 3.82; p-trend = 0.0006) for all-cause mortality and 3.28 (95% confidence interval: 1.77, 6.08; p-trend < 0.0001) for cardiovascular mortality. This association was present among both sexes and persisted in subgroup analyses by categories of diabetes duration, smoking, body mass index, proteinuria, and retinopathy. These data suggest that hyperglycemia is associated with all-cause and cardiovascular mortality among individuals with type 1 diabetes.

cardiovascular diseases; diabetes mellitus, type 1; glycosylation; hyperglycemia; mortality; Wisconsin


Abbreviations: CI, confidence interval; DCCT, Diabetes Control and Complications Trial; EDIC, Epidemiology of Diabetes Interventions and Complications; eGFR, estimated glomerular filtration rate; WESDR, Wisconsin Epidemiologic Study of Diabetic Retinopathy


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