Type 1 Diabetes and Coronary Artery Disease
- Trevor J. Orchard, MBBCH, MMEDSCI1,
- Tina Costacou, PHD1,
- Adam Kretowski, MD23 and
- Richard W. Nesto, MD4
- 1Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania
- 2Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Aurora, Colorado
- 3Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
- 4Department of Cardiovascular Medicine, Lahey Clinic Medical Center, Burlington, Massachusetts
- Address correspondence and reprint requests to Trevor J. Orchard, MBBCh, MMedSci, Diabetes and Lipid Research Bldg., 3512 Fifth Ave., Pittsburgh, PA 15213. E-mail: tjo{at}pitt.edu
- ACS, acute coronary syndrome
- ADA, American Diabetes Association
- AHA, American Hearth Association
- ApoA-IV, Apolipoprotein A-IV
- CAC, coronary artery calcification
- CAD, coronary artery disease
- CHD, coronary heart disease
- CVD, cardiovascular disease
- DCCT, Diabetes Control and Complications Trial
- ECG, electrocardiogram
- EDC, Epidemiology of Diabetes Complications
- EDIC, Epidemiology of Diabetes Interventions and Complications
- eGDR, estimated glucose disposal rate
- IL, interleukin
- IMT, intima-media thickening
- MI, myocardial infarction
- SMR, standardized mortality ratio
- TNF, tumor necrosis factor
- WESDR, Wisconsin Epidemiologic Study of Diabetic Retinopathy
Although the increased risk of premature heart disease in type 1 diabetes has been recognized for some time, the underlying pathogenesis is still poorly understood. The most likely factor, a priori, to account for this increased risk is hyperglycemia. However, despite recent evidence from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study that prior intensive glycemic control reduces cardiovascular disease (CVD), the epidemiologic association between glycemia and coronary heart disease (CHD) is surprisingly weak. This paradox is a focus of the current review, which also evaluates other major determinants of coronary artery disease (CAD) in type 1 diabetes, including the roles of insulin resistance, cytokines, inflammatory biomarkers, and, briefly, genetic factors. Finally, the clinical implications of this information are discussed.
THE MAGNITUDE OF THE PROBLEM—
A high occurrence of, and mortality from, CHD in type 1 diabetes has been documented since the late 1970s (1,2). A 1984 registry reported a 10-fold or greater CHD mortality compared with that expected from U.S. national data (3). This very high relative risk, partly reflecting the extremely low CHD death rate in the general young-adult population, was subsequently confirmed by Joslin investigators (4), who reported that those with type 1 diabetes by 55 years of age experienced a sixfold greater cumulative CHD mortality compared with the rate expected using Framingham Study data. The Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) also reported a standardized mortality ratio (SMR) from ischemic heart disease of 9.1 (for men) and 13.5 (for women) for those with a diabetes diagnosis before 30 years of age (5).
Two recent prospective epidemiologic studies, the Pittsburgh Epidemiology of Diabetes Complications (EDC) study (6) and Eurodiab (7), a multicenter, clinic-based study in Europe, confirmed these earlier reports and reported an incidence of total coronary events (including electrocardiogram [ECG] changes) …
