Natural History of Cardiovascular Disease in Patients With Diabetes
Role of hyperglycemia
- Zvonko Milicevic, MD, PHD1,
- Itamar Raz, MD2,
- Scott D. Beattie, PHD3,
- Barbara N. Campaigne, PHD3,
- Samiha Sarwat, MS3,
- Elwira Gromniak, MD4,
- Irina Kowalska, MD5,
- Edvard Galic, MD6,
- Meng Tan, MD3 and
- Markolf Hanefeld, MD, PHD7
- 1Eli Lilly Regional Operations, Vienna, Austria
- 2Department of Endocrinology, Hadassah Hospital, Ein Kerem, Jerusalem, Israel
- 3Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana
- 4Department of Endocrinology, Hypertension and Metabolic Diseases, Pomeranian Medical University, Szczecin, Poland
- 5Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
- 6Klinical Hospital Sveti Duh, Zagreb, Croatia
- 7Centre 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
Abstract
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.
- 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
Footnotes
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Z.M., S.D.B., B.N.C., S.S., and M.T. are employed by Eli Lilly and own stock in this company. E.G. has received honoraria for speaking engagements from Eli Lilly. I.K. has received honoraria for attending a symposium, speaking engagements, and consulting services from Eli Lilly. M.H. has received honoraria for speaking engagements from Bayer and has served on an advisory board for GlaxoSmithKline.
This article is based on a presentation at the 1st World Congress of Controversies in Diabetes, Obesity and Hypertension (CODHy). The Congress and the publication of this article were made possible by unrestricted educational grants from MSD, Roche, sanofi-aventis, Novo Nordisk, Medtronic, LifeScan, World Wide, Eli Lilly, Keryx, Abbott, Novartis, Pfizer, Generx Biotechnology, Schering, and Johnson & Johnson.
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