title: [Effect of ACE gene polymorphism on carbohydrate metabolism, on oxidative stress and on end-organ damage in type-2 diabetes mellitus].
abstract: ACE gene insertion/deletion (I/D) polymorphism is a well-known risk factor of hypertension, cardiovascular diseases and progression of diabetic nephropathy. In carriers of allele D, serum level of angiotensin-II is higher, which can be associated with increased oxidative stress and subsequent endothelial damage. Albuminuria is a sensitive marker of endothelial damage, while serum activity of the enzyme gamma-glutamyl transferase--that plays important role in the antioxidant defense--may refer to the level of oxidative stress. The present paper reports on a cross-sectional clinical study, where authors have examined on the relation between ACE gene insertion/deletion polymorphism and carbohydrate metabolism, hypertension as well as albuminuria in type 2 diabetics (n = 145). In patients carrying allele D, fructosamine levels were significantly higher (p = 0.007) than in carriers of allele I. Patients with II + ID genotypes and those who were treated with insulin took more antihypertensive drugs than the ones with II genotype or orally treated (p = 0.015). They found a significant association between genotype and fructosamine level (p = 0.023). Association between genotype or modality of treatment of diabetes (oral vs, insulin) and combined treatment of hypertension (number of antihypertensive drugs) was of borderline significance. They found that fructosamin level of patients receiving ACE inhibitor was lower than that of patients not receiving ACE inhibitors. In patients with allele D, they have also found higher activity of gamma-GT and higher albuminuria. From this results and data of the literature the authors conclude that because of insulin resistance (in connection with the presence of allele D), these patients tend to have a worse metabolic state, more advanced glycation products, due to which oxidative stress and endothelial cell damage may develop. As albuminuria and activity of gamma-GT were both found higher in patients with allele D, and our patients did not suffer of any hepatic disease, authors take the consequence that gamma-GT is a marker of the oxidative stress caused by allele D. Endothelial damage may explain that these patients take a higher number of antihypertensive combination. Based on this, D allele may contribute--via increased glycation and oxidative stress--to the target organ damage in type 2 diabetes.
authors.affiliation: Pécsi Tudományegyetem, Altalános Orvostudományi Kar, II. Belgyógyászati Klinika és Nephrologiai Centrum. gergo.molnar@aok.pte.hu
authors.forename: Gergö Attila
authors.initials: GA
authors.lastname: Molnár
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Wagner
authors.forename: László
authors.initials: L
authors.lastname: Wagner
authors.forename: Béla
authors.initials: B
authors.lastname: Melegh
authors.forename: Tamás
authors.initials: T
authors.lastname: Kószegi
authors.forename: Péter
authors.initials: P
authors.lastname: Degrell
authors.forename: Judit
authors.initials: J
authors.lastname: Bene
authors.forename: Mónika
authors.initials: M
authors.lastname: Tamaskó
authors.forename: Boglárka
authors.initials: B
authors.lastname: Laczy
authors.forename: Judit
authors.initials: J
authors.lastname: Nagy
authors.forename: István
authors.initials: I
authors.lastname: Wittmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D050260:Carbohydrate Metabolism; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D019270:Fructosamine / Q000097:blood; D017353:Gene Deletion; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D006978:Hypertension, Renovascular / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D018384:Oxidative Stress / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D000959:Antihypertensive Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D019270:Fructosamine; D007703:Peptidyl-Dipeptidase A