Introduction Hyperglycaemia occurs in every patient with diabetes mellitus. It is one of the leading factors in the development of diabetic complications. However, even in patients with similar blood glu- cose control, onset, severity and the progression of macrovascu- lar complications show large interindividual variations. The fa- milial occurrence of diabetic nephropathy in type 1 [1] and type 2 [2] diabetes and the finding that only 25 % ± 40 % of patients with diabetes mellitus develop diabetic nephropathy [3 ± 4] both suggest a genetic predisposition towards diabetic nephro- pathy. Since cardiovascular complications of diabetes mellitus are the main reasons for diabetes associated deaths especially due to silent ischemia or sudden cardiac death [5 ± 7], the identi- fication of coronary heart disease risk stratification parameters in these patients is of great interest. The introduction of angiotensin-converting-enzyme inhibitors into the therapy of hypertension and heart failure resulted in a 22% reduction in myocardial infarction, stroke or death from car- diovascular causes, especially in patients with diabetes mellitus [8 ± 9]. ACE inhibitors also seem to prevent cardiovascular events in patients with diabetes mellitus [10]. However, 27% to 50% non-responders to the ACE-Inhibitor therapy, as determined by lack of blood pressure-lowering effects, have been reported [11±13]. A polymorphism in the angiotensin-converting-en- zyme gene ACE gene) results in either the presence Insertion, I) or the absence Deletion, D) of a 287 base-pair fragment in in- No Association Between the Angiotensin-Converting- Enzyme Gene Insertion/Deletion Polymorphism and the Occurrence of Macroangiopathy in Patients with Diabetes Mellitus Type 2 T. Klemm 1 S. Mittrach-Schorin 1 S. Neumann 1 T. Gerike 2 H. Krankenberg 3 G. Schuler 3 R. Paschke 1 Affiliation 1 III. Medical Department, Leipzig University, Leipzig, Germany 2 Institute of Medical Informatics, Statistics and Epidemiology, Leipzig University, Leipzig, Germany 3 Leipzig Heart Centre GmbH, Leipzig, Germany Correspondence R. Paschke, M.D. ´ III. Medical Department ´ Leipzig University ´ Philipp-Rosenthal-Strasse 27 ´ 04103 Leipzig ´ Germany ´ Phone: + 49 341) 971 32 00 ´ Fax: + 49 341) 971 32 09 ´ E-Mail: Pasr@server3.medizin.uni-leipzig.de Received 16 May 2002 ´ Accepted after revision 30 July 2002 Bibliography Horm Metab Res 2003; 35: 43±47  Georg Thieme Verlag Stuttgart ´ New York ´ ISSN 0018-5043 Abstract Previous studies have reported an association between the ACE- I/D-polymorphism and coronary heart disease CHD) in patients with diabetes mellitus. However, ACE inhibitor treatment, which could have compensated for negative effects of the D/D form of the ACE gene polymorphism, was not considered in the studies. We investigated the influence of the ACE-I/D polymorphism and the ACE inhibitor treatment in patients with diabetes mellitus on the occurrence of CHD by multiple-regression analysis. Distribu- tion of the ACE gene I/D-polymorphism was investigated in 691 patients with diabetes mellitus prospectively characterised for the presence/absence of coronary heart disease. The distribution of DD; ID; II genotypes was 105 vs. 202 vs. 102 25.7% vs. 49.4% vs. 24.9) in the CHD + group and 55 vs. 160 vs. 67 19.5 % vs. 56.7 % vs. 23.8 %) in the CHD ± group, respectively p = 0.1). A multiple logistic regression analysis introducing the typical risk factors for CHD age, gender, smoking, BMI > 26 kg/m 2 , LDL elevation, HbA1c > 7 %) could not identify the ACE gene I/D-polymorphism as an independent risk factor for CHD p = 0.87). Our data there- fore suggest that the ACE gene I/D polymorphism is not associat- ed with the occurrence of diabetic macroangiopathy in patients with or without treatment of ACE inhibitors. Key words Diabetes ´ Genetics ´ Complications of Diabetes Original Clinical 43