Modulation of the Renal Response to ACE Inhibition by ACE Insertion/Deletion Polymorphism During Hyperglycemia in Normotensive, Normoalbuminuric Type 1 Diabetic Patients

• Published in: Diabetes (New York, N.Y.) Vol. 54; no. 10; pp. 2961 - 2967
• Main Authors: WEEKERS, Laurent, BOUHANICK, Béatrice, MARRE, Michel, HADJADJ, Samy, GALLOIS, Yves, ROUSSEL, Ronen, PEAN, Franck, ANKOTCHE, Amos, CHATELLIER, Gilles, ALHENC-GELAS, Francois, LEFEBVRE, Pierre J
• Format: Journal Article Web Resource
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.10.2005; Amer Diabetes Assoc
• Subjects: Adult; Albuminuria; Aldosterone - blood; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Biological and medical sciences; Blood Pressure; Chromosome aberrations; Diabetes; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - enzymology; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; Diabetic nephropathy; Drug therapy; Endocrine pancreas. Apud cells (diseases); Endocrinologie, métabolisme & nutrition; Endocrinology, metabolism & nutrition; Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Gene Deletion; Genetic polymorphisms; Genotype; Genotype & phenotype; Glomerular Filtration Rate; Glucose; Hemodynamics; Human health sciences; Humans; Hyperglycemia; Hyperglycemia - enzymology; Hypertension; Insulin; Kidney - blood supply; Kidney - drug effects; Male; Medical genetics; Medical sciences; Mutagenesis, Insertional; Peptidyl-Dipeptidase A - blood; Peptidyl-Dipeptidase A - genetics; Plasma; Polymorphism; Polymorphism, Genetic; Ramipril - therapeutic use; Renin - blood; Sciences de la santé humaine; Type 1 diabetes; Urine; France; Endocrinopathy; Human; Immunopathology; Hyperglycemia; Type 1 diabetes; Deletion; Autoimmune disease; Inhibition; Polymorphism
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/diabetes.54.10.2961

Modulation of the Renal Response to ACE Inhibition by ACE Insertion/Deletion Polymorphism During Hyperglycemia in Normotensive, Normoalbuminuric Type 1 Diabetic Patients Laurent Weekers 1 , Béatrice Bouhanick 2 , Samy Hadjadj 3 4 , Yves Gallois 5 , Ronen Roussel 6 7 , Franck Pean 7 , Amos Ankotche 6 , Gilles Chatellier 8 , François Alhenc-Gelas 9 , Pierre J. Lefebvre 1 and Michel Marre 6 7 1 Division of Diabetes, Nutrition, and Metabolic Disorders, Department of Medicine, Centre Hospitalier Universitaire du Sart Tilman, Liege, Belgium 2 Médecine Interne et Risque Vasculaire, Rangueil Hospital, Toulouse, France 3 Department of Endocrinology and Diabetology, University Hospital, Poitiers Cedex, France 4 Institut National de la Santé et de la Recherche Médicale (INSERM) ERM 324, University Hospital, Poitiers Cedex, France 5 Biochimie, Faculté de Médecine d’Angers, Angers Cedex, France 6 Department of Endocrinology, Diabetology and Nutrition, Bichat Hospital, Assistance Publique des Hôpitaux de Paris, Paris Cedex, France 7 INSERM U695, Université Paris VII Faculté de Médecine X Bichat, Paris, France 8 Department of Biostatistics, Georges Pompidou European Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France 9 INSERM U367/652, Paris, France Address correspondence and reprint requests to Michel Marre, Department of Endocrinology, Diabetology and Nutrition, Bichat Hospital, Assistance Publique des Hôpitaux de Paris, 46 rue Henri Huchard, 75877 Paris Cedex 18, France. E-mail: michel.marre{at}bch.ap-hop-paris.fr Abstract ACE inhibition protects kidney function, but ACE insertion/deletion (I/D) polymorphism affects renal prognosis in type 1 diabetic patients. ACE genotype may influence the renal benefits of ACE inhibition. We studied the impact of ACE I/D polymorphism on the renal hemodynamic changes induced by ACE inhibition in type 1 diabetes. We studied renal hemodynamics (glomerular filtration rate [GFR], effective renal plasma flow [ERPF], filtration fraction [GFR/ERPF], mean arterial pressure [MAP], and total renal resistances [MAP/ERPF]) repeatedly during normoglycemia and then hyperglycemia in 12 normotensive, normoalbuminuric type 1 diabetes and the II genotype (associated with nephroprotection) versus 22 age- and sex-matched subjects with the ACE D allele after three randomly allocated 2- to 6-week periods on placebo, 1.25 mg/day ramipril, and 5 mg/day ramipril in a double-blind, cross-over study. During normoglycemia, the hemodynamic changes induced by ramipril were similar in both genotypes. During hyperglycemia, the changes induced by ramipril were accentuated in the II genotype group and attenuated dose dependently in the D allele group (treatment-genotype interaction P values for ERPF, 0.018; MAP, 0.018; and total renal resistances, 0.055). These results provide a basis to different renal responses to ACE inhibition according to ACE genotype in type 1 diabetes. ERPF, effective renal plasma flow GFR, glomerular filtration rate I/D, insertion/deletion MAP, mean arterial pressure TRR, total renal resistance UAE, urinary albumin excretion Footnotes L.W., B.B., and S.H. contributed equally to this work. Accepted July 5, 2005. Received May 27, 2005. DIABETES