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Our findings confirm the higher mortality and incidence of pump failure in acute myocardial infarction with co-morbid diabetes. They suggest that the less frequent use of thrombolytic therapy, lower reperfusion rates, and more advanced coronary artery disease might be contributory. The presence of autonomic neuropathy and microvascular disease probably also contribute to poor outcome; other major diabetic complications and diabetic control did not influence outcome.

OBJECTIVE -To investigate whether the DD genotype is a predictor of mortality and of the decline in renal function in patients with type 2 diabetes and established nephropathy. RESEARCH DESIGN AND METHODS-A total of 56 such patients of Maltese Caucasian descent were recruited, and their ACE genotype was determined. Serum creatinine was estimated approximately every 4 months. The glomerular filtration rate (GFR) was calculated according to the Cockroft-Gault formula, and rate of change was determined by regression analysis.RESULTS -The rate of change in calculated GFR was Ϫ7.76 ml ⅐ min -1 ⅐ year -1 in those with the DD genotype (n ϭ 31) and Ϫ1.17 ml ⅐ min -1 ⅐ h -1 in those with the ID or II genotype (n ϭ 25) (P Ͻ 0.01). The 3-year mortality was 45.2% in the DD group compared with 20.0% in the ID/II group (P Ͻ 0.05).CONCLUSIONS -The DD genotype of the ACE gene polymorphism is associated with a more rapid decline in renal function and higher mortality in type 2 diabetic patients with established nephropathy. Diabetes Care 24:2115-2120, 2001D iabetic nephropathy is one of the major long-term complications of diabetes. However, it is impossible to predict which patients will develop this complication. Although duration of diabetes, blood pressure, and glycemic control are undoubtedly important, other factors are probably also involved. There is considerable evidence of familial clustering of nephropathy in type 1 diabetes (1-3). Data on Pima Indians (4), as well as our own data in patients of Maltese Caucasian descent (5), have shown that familial clustering also occurs in type 2 diabetic nephropathy. This suggests that genetic factors may be involved in the etiology of renal disease in both major types of diabetes.One possible genetic factor that has attracted much attention is the ACE gene. This contains a polymorphism comprised of the presence (insertion, I) or absence (deletion, D) of a 287-bp sequence within intron 16 (6). The polymorphism has been associated with diabetic nephropathy in type 1 and type 2 diabetes by some but not all authors (7); however, two recent meta-analyses have confirmed an association of the DD genotype with diabetic nephropathy (8,9). The rate of decline of renal function has been shown to be more rapid in type 1 diabetic patients who have the DD genotype (10). Two studies in type 2 diabetes have had similar results (11,12). Patients with diabetic nephropathy are known to have a high mortality, mostly resulting from cardiovascular disease (13,14). Tarnow et al. (15) recently reported increased mortality in parents of type 1 diabetic patients with nephropathy compared with parents of type 1 diabetic patients without nephropathy, suggesting a genetic predisposition to the increased mortality observed in patients with diabetic nephropathy. The DD genotype of the ACE polymorphism has been associated with left ventricular hypertrophy (LVH) in the general population (16). It has also been associated with coronary artery disease in both type 1 (17) and type 2 (18,19) diabetes. In addition, ...

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