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(Circulation. 2002;105:2008.)
© 2002 American Heart Association, Inc.

Editorial

Do Increased Proinsulin Concentrations Explain the Excess Risk of Coronary Heart Disease in Diabetic and Prediabetic Subjects?

Steven M. Haffner, MD; Anthony J.G. Hanley, PhD

University of Texas Health Science Center at San Antonio, San Antonio, Tex, and Leadership Sinai Centre for Diabetes, Mt Sinai Hospital, Toronto, Ontario, Canada.

Reprint requests to Steven M. Haffner, MD, Professor, University of Texas Health Science Center at San Antonio, Department of Medicine, 7703 Floyd Curl Drive MC 7873, San Antonio, TX 78229-3900. E-mail haffner@uthscsa.edu

Key Words: Editorials • epidemiology • coronary disease • diabetes

Type 2 diabetes is associated with a marked increase in the risk of coronary heart disease (CHD).¹ In addition, small increases in glucose concentrations in the nondiabetic range also may be associated with an increased risk of CHD (see the Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Europe [DECODE] study²). However, the increase in CHD in diabetic subjects may not be entirely due to increases in glucose levels per se, because in many studies, including the United Kingdom Prospective Diabetes Study (UKPDS),³ although glucose levels were significantly related to CHD, the magnitude of the association is only modest. One explanation for the increased risk of CHD in diabetics may be the insulin resistance syndrome.⁴ A related possibility may be the atherogenicity of the prediabetic state.⁴ Indeed, insulin resistance, rather than decreased insulin secretion, seems to be most responsible for the increased cardiovascular risk factors in the prediabetic state (ie, increased triglyceride and blood pressure and decreased high-density lipoprotein cholesterol [HDL-C] even before the onset of diabetes).⁵ In some studies, insulin concentrations (as a surrogate for insulin resistance) have been strongly related to CHD⁶; however, in other studies that include meta-analysis, insulin concentrations have been only modestly associated with CHD.⁷

See Circulation. 2002;105:1311–1316

Until recently, most insulin immunoassays cross-reacted with proinsulin. Proinsulin is a precursor of insulin that is enzymatically cleaved to form insulin. Several studies have suggested that proinsulin concentrations may be more strongly related to cardiovascular risk factors (especially increased blood pressure and higher triglyceride . . . [Full Text of this Article]

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				J. S. Yudkin Increased Proinsulin Concentrations and Excess Risk of Coronary Heart Disease in Patients With Diabetes and Prediabetes Circulation, December 10, 2002; 106 (24): e202 - e202. [Full Text] [PDF]