Insulin Resistance–Related Factors, but not Glycemia, Predict Coronary Artery Disease in Type 1 Diabetes
10-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications study
- Trevor J. Orchard, MBBCH, MMEDSCI1,
- Jon C. Olson, DRPH1,
- John R. Erbey, PHD1,
- Katherine Williams, MD1,
- Kimberly Y.-Z. Forrest, PHD1,
- Leslie Smithline Kinder, PHD2,
- Demetrius Ellis, MD3 and
- Dorothy J. Becker, MBBCH3
- 1Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
- 2School of Medicine, Stanford University, Palo Alto, California
- 3Department of Pediatrics, Division of Endocrinology and Metabolism, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
OBJECTIVE—To determine the independent risk factors for coronary artery disease (CAD) in type 1 diabetes by type of CAD at first presentation.
RESEARCH DESIGN AND METHODS—This is a historical prospective cohort study of 603 patients with type 1 diabetes diagnosed before 18 years of age between 1950 and 1980. The mean age and duration of diabetes at baseline were 28 (range 8–47) and 19 years (7–37), respectively, and patients were followed for 10 years. Patients with prevalent CAD were excluded from the study. Electrocardiogram (ECG) ischemia was defined by Minnesota Code (MC) 1.3, 4.1–3, 5.1–3, or 7.1; angina was determined by Pittsburgh Epidemiology of Diabetes Complications (EDC) study physician diagnosis; and hard CAD was determined by angiographic stenosis ≥50%, revascularization procedure, Q waves (MC 1.1–1.2), nonfatal myocardial infarction (MI), or CAD death.
RESULTS—A total of 108 incident CAD events occurred during the 10-year follow-up: 17 cases of ECG ischemia, 49 cases of angina, and 42 cases of hard CAD (5 CAD deaths, 25 nonfatal MI or major Q waves, and 12 revascularization or ≥50% stenosis). Blood pressure, lipid levels, inflammatory markers, renal disease, and peripheral vascular disease showed a positive gradient across the groups of no CAD, angina, and hard CAD (P < 0.01, trend analysis, all variables), although estimated glucose disposal rate (eGDR) and physical activity showed inverse associations (P < 0.01, trend analysis, both variables). In addition, depressive symptomatology predicted angina (P = 0.016), whereas HbA1 showed no association with subsequent CAD.
CONCLUSIONS—These data suggest that although the standard CAD risk factors are still operative in type 1 diabetes, greater glycemia does not seem to predict future CAD events. In addition, depressive symptomatology predicts angina and insulin resistance (eGDR) predicts hard CAD end points.
- ABD, ankle-brachial difference
- ABI, ankle-brachial index
- AER, albumin excretion rate
- ApoA1, apolipoprotein A1
- BDI, Beck Depression Inventory
- CAD, coronary artery disease
- DCCT, Diabetes Control and Complications Trial
- DSP, distal symmetric polyneuropathy
- ECG, electrocardiogram
- EDC, Epidemiology of Diabetes Complications
- eGDR, estimated glucose disposal rate
- E/I, expiration/inspiration
- LEAD, lower extremity arterial disease
- MA, microalbuminuria
- MC, Minnesota Code
- ON, overt nephropathy
- WBC, white blood cell count
Address correspondence and reprint requests to Trevor J. Orchard, MBBCh, MMedSci, Diabetes and Lipid Research Building, 3512 Fifth Ave., Pittsburgh, PA 15213. E-mail:.
Received for publication 10 October 2002 and accepted in revised form 20 December 2002.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
See accompanying editorial, p. 1629.
- DIABETES CARE