Affiliation:
1. 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
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 m
2
) and ERPF (636±69 mL/min per 1.73 m
2
) of II subjects declined by 8±10% and 10±9%, respectively, during hyperglycemia; whereas baseline GFR (138±16 mL/min per 1.73 m
2
) and ERPF (607±93 mL/min per 1.73 m
2
) 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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Cited by
31 articles.
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