This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Marre, M. Articles by Alhenc-Gelas, F. Search for Related Content PubMed PubMed Citation Articles by Marre, M. Articles by Alhenc-Gelas, F. Related Collections Cardio-renal physiology/pathophysiology Functional genomics Other etiology

(Hypertension. 1999;33:775-780.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Renal Changes on Hyperglycemia and Angiotensin-Converting Enzyme in Type 1 Diabetes

Michel Marre; Béatrice Bouhanick; Gilles Berrut; Yves Gallois; Jean-Jacques Le Jeune; Gilles Chatellier; Joël Menard; François Alhenc-Gelas

From Médecine B (M.M., B.B., G.B.), University Hospital, Angers; Institut National de la Santé et de la Recherche Médicale U367 (M.M, F.A.-G.), Paris; Biochemistry Department (Y.G.) and Nuclear Medicine Department (J.-J. Le J.), University Hospital, Angers; and Medical Informatics (G.C.), Broussais Hospital, Paris, France.

Abstract—Hyperglycemia causes capillary vasodilation and high glomerular capillary hydraulic pressure, which lead to glomerulosclerosis and hypertension in type 1 diabetic subjects. The insertion/deletion (I/D) polymorphism of the angiotensin I–converting enzyme (ACE) gene can modulate risk of nephropathy due to hyperglycemia, and the II genotype (producing low plasma ACE concentrations and probably reduced renal angiotensin II generation and kinin inactivation) may protect against diabetic nephropathy. We tested the possible interaction between ACE I/D polymorphism and uncontrolled type 1 diabetes by measuring glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) during normoglycemia (5 mmol/L) and hyperglycemia (15 mmol/L) in 9 normoalbuminuric, normotensive type 1 diabetic subjects with the II genotype and 18 matched controls with the ID or DD genotype. Baseline GFR (145±22 mL/min per 1.73 m²) and ERPF (636±69 mL/min per 1.73 m²) of II subjects declined by 8±10% and 10±9%, respectively, during hyperglycemia; whereas baseline GFR (138±16 mL/min per 1.73 m²) and ERPF (607±93 mL/min per 1.73 m²) increased by 4±7% and 6±11%, respectively, in ID and DD subjects (II versus ID or DD subjects: P=0.0007 and P=0.0005, for GFR and ERPF, respectively). The changes in renal hemodynamics of subjects carrying 1 or 2 D alleles were compatible, with a mainly preglomerular vasodilation induced by hyperglycemia, proportional to plasma ACE concentration (P=0.024); this was not observed in subjects with the II genotype. Thus, type 1 diabetic individuals with the II genotype are resistant to glomerular changes induced by hyperglycemia, providing a basis for their reduced risk of nephropathy.

Key Words: glomerular disease • diabetic nephropathy • genetics • angiotensin-converting enzyme

This article has been cited by other articles:

				B. Volkan-Salanci, S. Dagdelen, M. Alikasifoglu, T. Erbas, M. Hayran, and B. Erbas Impact of renin-angiotensin system polymorphisms on renal haemodynamic responsiveness to acute angiotensin-converting enzyme inhibition in type 2 diabetes mellitus Journal of Renin-Angiotensin-Aldosterone System, March 1, 2009; 10(1): 41 - 50. [Abstract] [PDF]

				P. Ruggenenti, P. Bettinaglio, F. Pinares, and G. Remuzzi Angiotensin Converting Enzyme Insertion/Deletion Polymorphism and Renoprotection in Diabetic and Nondiabetic Nephropathies Clin. J. Am. Soc. Nephrol., September 1, 2008; 3(5): 1511 - 1525. [Abstract] [Full Text] [PDF]

				L. Weekers, B. Bouhanick, S. Hadjadj, Y. Gallois, R. Roussel, F. Pean, A. Ankotche, G. Chatellier, F. Alhenc-Gelas, P. J. Lefebvre, et al. Modulation of the Renal Response to ACE Inhibition by ACE Insertion/Deletion Polymorphism During Hyperglycemia in Normotensive, Normoalbuminuric Type 1 Diabetic Patients Diabetes, October 1, 2005; 54(10): 2961 - 2967. [Abstract] [Full Text] [PDF]

				F. G. H. van der Kleij, P. E. de Jong, R. H. Henning, D. de Zeeuw, and G. Navis Enhanced Responses of Blood Pressure, Renal Function, and Aldosterone to Angiotensin I in the DD Genotype Are Blunted by Low Sodium Intake J. Am. Soc. Nephrol., April 1, 2002; 13(4): 1025 - 1033. [Abstract] [Full Text]

				S. HADJADJ, R. BELLOUM, B. BOUHANICK, Y. GALLOIS, G. GUILLOTEAU, G. CHATELLIER, F. ALHENC-GELAS, and M. MARRE Prognostic Value of Angiotensin-I Converting Enzyme I/D Polymorphism for Nephropathy in Type 1 Diabetes Mellitus: A Prospective Study J. Am. Soc. Nephrol., March 1, 2001; 12(3): 541 - 549. [Abstract] [Full Text]

				S. Y. Osei, D. A. Price, L. M. B. Laffel, M. C. Lansang, and N. K. Hollenberg Effect of Angiotensin II Antagonist Eprosartan on Hyperglycemia-Induced Activation of Intrarenal Renin-Angiotensin System in Healthy Humans Hypertension, July 1, 2000; 36(1): 122 - 126. [Abstract] [Full Text] [PDF]