Renal changes on hyperglycemia and angiotensin-converting enzyme in type 1diabetes

Hyperglycemia causes capillary vasodilation and high glomerular capillary h ydraulic pressure, which lead to glomerulosclerosis and hypertension in typ e 1 diabetic subjects. The insertion/deletion (I/D) polymorphism of the ang iotensin I-converting enzyme (ACE) gene can modulate risk of nephropathy du e to hyperglycemia, and the II genotype (producing low plasma ACE concentra tions and probably reduced renal angiotensin II generation and kinin inacti vation) may protect against diabetic nephropathy. We tested the possible in teraction between ACE I/D polymorphism and uncontrolled type I diabetes by measuring glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) during normoglycemia (approximate to 5 mmol/L) and hyperglycemia (ap proximate to 15 mmol/L) in 9 normoalbuminuric, normotensive type I diabetic subjects with the II genotype and 18 matched controls with the ID or DD ge notype, 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%, respecti vely, 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 he modynamics of subjects carrying 1 or 2 D alleles were compatible, with a ma inly preglomerular vasodilation induced by hyperglycemia, proportional to p lasma ACE concentration (P=0.024); this was not observed in subjects with t he II genotype. Thus, type I diabetic individuals with the II genotype are resistant to glomerular changes induced by hyperglycemia, providing a basis for their reduced risk of nephropathy.