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

  1. Laurent Weekers1,
  2. Béatrice Bouhanick2,
  3. Samy Hadjadj34,
  4. Yves Gallois5,
  5. Ronen Roussel67,
  6. Franck Pean7,
  7. Amos Ankotche6,
  8. Gilles Chatellier8,
  9. François Alhenc-Gelas9,
  10. Pierre J. Lefebvre1 and
  11. Michel Marre67
  1. 1Division of Diabetes, Nutrition, and Metabolic Disorders, Department of Medicine, Centre Hospitalier Universitaire du Sart Tilman, Liege, Belgium
  2. 2Médecine Interne et Risque Vasculaire, Rangueil Hospital, Toulouse, France
  3. 3Department of Endocrinology and Diabetology, University Hospital, Poitiers Cedex, France
  4. 4Institut National de la Santé et de la Recherche Médicale (INSERM) ERM 324, University Hospital, Poitiers Cedex, France
  5. 5Biochimie, Faculté de Médecine d’Angers, Angers Cedex, France
  6. 6Department of Endocrinology, Diabetology and Nutrition, Bichat Hospital, Assistance Publique des Hôpitaux de Paris, Paris Cedex, France
  7. 7INSERM U695, Université Paris VII Faculté de Médecine X Bichat, Paris, France
  8. 8Department of Biostatistics, Georges Pompidou European Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France
  9. 9INSERM U367/652, Paris, France
  1. 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.

Footnotes

  • L.W., B.B., and S.H. contributed equally to this work.

    • Accepted July 5, 2005.
    • Received May 27, 2005.
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This Article

  1. doi: 10.2337/diabetes.54.10.2961 Diabetes vol. 54 no. 10 2961-2967
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