ANGIOTENSIN-CONVERTING ENZYME GENE POLYMORPHISM AND RENAL HEMODYNAMICFUNCTION IN EARLY DIABETES

An insertion/deletion (VD) of the human angiotensin converting enzyme (ACE) gene is a major determinant of circulating ACE levels. Recent st udies suggest that the ACE I/D polymorphism may influence the risk of developing nephropathy in patients with insulin dependent diabetes mel litus (IDDM), although the mechanism responsible for the effect is unk nown. Since an early increase in glomerular filtration rate (GFR) may also be a risk factor for the development of diabetic nephropathy, we sought to determine if the ACE I/D polymorphism influenced renal hemod ynamic function in patients with IDDM. Genomic DNA was obtained from 3 9 normotensive male and female patients with uncomplicated IDDM (mean duration 3.4 years; range 1 to 6 years), and from 20 non diabetic cont rol subjects. The ACE IID polymorphism was determined using the polyme rase chain reaction. Subjects were divided into three groups based on their ACE genotype. Values for GFR, renal plasma flow (ERPF), filtrati on fraction, and renal vascular resistance were determined in both gro ups using classic inulin and paraaminohippurate clearance techniques. Blood glucose was maintained between 4 to 6 mmol/Iiter in the patients with IDDM using a modified euglycemic clamp technique. Mean values fo r GFR were significantly greater in patients homozygous for the I alle le (143 +/- 7 ml/min/1.73 m(2)) compared to patients homozygous for th e D allele (121 +/- 3 ml/min/1.73 m(2), P < 0.01), while the mean GFR values for the heterozygous patients were intermediate. ERPF was also significantly greater in patients homozygous for the I allele (850 +/- 103 ml/min/1.73 m(2)) compared to patients homozygous for the D allel e (672 +/- 31 ml/min/1.73 m(2), P < 0.04), while there were no differe nces in the values for mean arterial pressure, glycosylated hemoglobin , or albumin excretion rates amongst the groups. There was no dominant effect of the ACE gene VD polymorphism in the control group. These re sults suggest that: (1) the ACE gene VD polymorphism influences glomer ular filtration and renal plasma flow rates in patients with early unc omplicated IDDM; and (2) differences in renal hemodynamic function do not appear to explain the protection against the development of diabet ic nephropathy offered by the I allele.