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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 Ն50%, 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 Ն50% 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 Ͻ 0.01, trend analysis, all variables), although estimated glucose disposal rate (eGDR) and physical activity showed inverse associations (P Ͻ 0.01, trend analysis, both variables). In addition, depressive symptomatology predicted angina (P ϭ 0.016), whereas HbA 1 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. Diabetes Care 26:1374 -1379, 2003B oth type 1 and type 2 diabetes increase the risk of coronary artery disease (CAD) (1). However, the reasons underlying this are largely unknown, although renal disease (2) and the standard CAD risk factors seem important (3). The role of glycemic control is controversial; two studies (3,4) suggest little relationship to CAD, although others report such an association (5).Although it has been an accepted practice to consider all CAD manifestations together, because they are believed to be linked by the same underlying atherosclerosis, important differences have been noted in the Pittsburgh Epidemiology of Diabetes Complications (EDC) study of type 1 diabetes. This study suggested somewhat distinct pathophysiologic mechanisms; for example, depressive symptomatology was more related to morbidity than mortality (3).To further address these issues, risk factors, including glycemic control, for angina, ischemic electrocardiogram (ECG), and hard CAD (myocardial infarction [MI], CAD death, or angiographically proven stenosis) were investigated in this prospective study of type 1 diabetes using, for the first time, the ...

The inflammation of aging hypothesis purports that aging is the accumulation of damage, which results, in part, from chronic activation of inflammation process. We tested this hypothesis in relationship to fractures in 2985 men and women enrolled in the Health ABC study. Results showed that subjects with the greatest number of inflammatory markers have the highest risk of fracture.Introduction: Cytokines play major roles in regulating bone remodeling in the bone microenvironment, but their relationship to fractures is uncertain. Materials and Methods: The study population includes 2985 well-functioning white and black women and men (42%, black; 51%, women) 70-79 yr of age enrolled in the Health Aging and Body Composition Study. Inflammatory markers were measured in frozen serum using standardized assays. We measured interleukin (IL-6), TNF␣, C-reactive protein (CRP), and soluble receptors (IL-2 sR, IL-6 sR, TNF sR1and TNF sR2).Cytokine-soluble receptors were measured in a subset (n ‫ס‬ 1430). Total hip BMD was measured by DXA. During 5.8 ± 1.6 yr of 95% complete follow-up, incident fractures were confirmed in 268 subjects. The risk of fracture was compared among subjects with the highest inflammatory markers (quartile 4) versus lower levels (quartiles 1, 2, and 3) using proportional hazard models. Results and Conclusions: Subjects who fractured were more likely to be white and female. Baseline markers of inflammation were higher among subjects who subsequently experienced an incident fracture. In multivariate models, the relative risk of fracture (95% CIs) for subjects with the highest inflammatory markers (quartile 4) compared with those with lower inflammatory markers (quartiles 1, 2, and 3) was 1.34 (0.99, 1.82) for CRP; 1.28 (0.95-1.74) for IL-6; 1.28 (0.97-1.70) for TNF␣; 1.52 (1.04-2.21) for IL-2 sR; 1.33 (0.90-1.96) for IL-6 sR; 1.73 (1.18-2.55) for TNF sR1 and 1.48 (1.01-2.20) for TNF sR2. In subjects with three or more (out of seven) high inflammatory markers, the relative risk of fracture was 2.65 (1.44-4.89) in comparison with subjects with no elevated markers. (p trend ‫ס‬ 0.001). We conclude that elevated inflammatory markers are prognostic for fractures, extending the inflammation hypothesis of aging to osteoporotic fractures.