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Natural History of Cardiovascular Disease in Patients With Diabetes

Role of hyperglycemia

¹ Eli Lilly Regional Operations, Vienna, Austria
² Department of Endocrinology, Hadassah Hospital, Ein Kerem, Jerusalem, Israel
³ Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana
⁴ Department of Endocrinology, Hypertension and Metabolic Diseases, Pomeranian Medical University, Szczecin, Poland
⁵ Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
⁶ Klinical Hospital Sveti Duh, Zagreb, Croatia
⁷ Centre for Clinical Studies, GWT, Technical University Dresden, Dresden, Germany

Address correspondence and reprint requests to Zvonko Milicevic, MD, PhD, Eli Lilly Regional Operations, Vienna, Austria. E-mail: milicevic_zvonko{at}lilly.com

Atherosclerotic vascular disease is more common in diabetic than in nondiabetic individuals. Diabetic macrovascular disease also has a more severe course with greater prevalence of multiple-vessel coronary artery disease and more diffuse elongated atheromas in affected blood vessels. In this review, we discuss possible reasons for increased incidence of cardiovascular (CV) events in individuals with diabetes. Although an increased prevalence of standard CV risk factors has been clearly documented in association with diabetes, diabetes-related abnormalities, particularly hyperglycemia, also play an important role. Epidemiological studies suggest that the effect of hyperglycemia on CV risk is independent of other known risk factors, but no data from primary interventional trials are available yet. Analysis of datasets from populations that included individuals with impaired glucose tolerance and impaired fasting glucose suggest that the pathogenic role of hyperglycemia on the blood vessel wall already exists in the early stages of glucose intolerance. The effect of postprandial or postchallenge hyperglycemia seems to be greater than the effect of fasting blood glucose abnormalities. The relationship of postprandial glycemia, fasting blood glucose, and CV risk in individuals with diagnosed (or overt) diabetes is less clear, although most reports indicate a greater pathogenic potential of postprandial hyperglycemia rather than fasting hyperglycemia. Based on the results of epidemiological reports, the most appropriate targets in interventional trials are postprandial hyperglycemia or A1C.

Abbreviations: BG, blood glucose • CV, cardiovascular • DCCT, Diabetes Control and Complications Trial • EDIC, Epidemiology of Diabetes Interventions and Complications • FBG, fasting blood glucose • IGT, impaired glucose tolerance • MI, myocardial infarction

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