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The Relationship of Fasting Serum Radioimmune Insulin Levels to Incident Coronary Heart Disease in an Insulin-Treated Diabetic Cohort

Department of Biostatistics, University of Washington (R.A.K.), Seattle, Washington 98115; Kaiser Permanente of Georgia and Division of Endocrinology, Emory University (J.I.B.), Atlanta, Georgia 30082; Department of Pathology and Biochemistry, University of Vermont College of Medicine (R.P.T.), Colchester, Vermont 05446; Division of Epidemiology and Clinical Applications, National Heart, Lung, Blood Institute, National Institutes of Health (P.J.S.), Bethesda, Maryland 20892; Department of Epidemiology, Graduate School of Public Health (T.J.O.), University of Pittsburgh, Pittsburgh, Pennsylvania 15251; and Department of Public Health Sciences, Wake Forest University School of Medicine (G.L.B.), Winston-Salem, North Carolina 27157

Address all correspondence and requests for reprints to: Richard A. Kronmal, Ph.D., University of Washington, Department of Biostatistics Cardiovascular Health Study Coordinating Center Building 29, Suite 310, 6200 NE 74th Street, Seattle, Washington 98115. E-mail: kronmal{at}u.washington.edu.

It is not known whether insulin levels, in the setting of insulin treatment, are an independent risk factor for coronary heart disease (CHD). We studied a cohort of 116 insulin-treated individuals, 65 yr or older, who were followed for 5.6–9 yr. All were free of CHD at baseline.

There were 47 incident CHD events. In Cox proportional hazards modeling, with fasting immune-reactive insulin levels as a continuous variable, the hazard ratio for CHD was statistically significant (P < 0.0001). When insulin levels were divided into intervals, those in the third interval [43–150 µU/ml (258–900 pmol/liter)] had an adjusted 30% increased relative risk (95% confidence interval, 0.57, 2.98) compared with those in the first interval [<20 µU/ml (<120 pmol/liter)]. Those in the fourth interval [151–400 µU/ml (906–2400 pmol/liter)] had an adjusted 5.6-fold increased risk (2.3–13.1; P < 0.0001). Approximately 15% of the cohort had such elevated insulin levels. Immune-reactive insulin levels were strongly correlated with specific insulin, proinsulin, and insulin antibody levels.

Markedly elevated fasting immune-reactive insulin levels were an independent risk factor for CHD in this study of insulin-treated older adults. These observational findings should be confirmed through larger prospective studies, given their implications for insulin therapy.

This work was supported by contracts NO1-HC-85079 through NO1-HC-85086, NO1-HC-35129, and NO1-HC-15103 from the National Heart, Lung, and Blood Institute.

Abbreviations: CHD, Coronary heart disease; CHS, Cardiovascular Health Study; CV, coefficient of variance; DM, diabetes mellitus; ECG, electrocardiogram; HDL, high-density lipoprotein; IMT, intimal-medial thickness; MI, myocardial infarction; PAI-1, type-1 plasminogen activator inhibitor.

This article has been cited by other articles:

				R. Kronmal and J. Barzilay Authors' Response: The Relationship of Fasting Serum Radioimmune Insulin Levels to Incident Coronary Heart Disease in an Insulin-Treated Diabetic Cohort J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5869 - 5869. [Full Text] [PDF]

				P. Dandona, A. Chaudhuri, and A. Aljada The Relationship of Fasting Serum Radioimmune Insulin Levels to Incident Coronary Heart Disease in an Insulin-Treated Diabetic Cohort J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5868 - 5869. [Full Text] [PDF]