Relationship between glomerular hyperfiltration and ACE insertion/deletionpolymorphism in type 1 diabetic children and adolescents

OBJECTIVE - Glomerular hyperfiltration may predict diabetic nephropathy in type 1 diabetes, and some studies suggest that the ACE D allele is associat ed with diabetic nephropathy The aim of this study was to examine a possibl e relationship between glomerular hyperfiltration and ACE insertion/deletio n (I/D) polymorphism in type 1 diabetic children and adolescents. RESEARCH DESIGN AND METHODS - A cross-sectional study was conducted to exam ine the relationship between glomerular hyperfiltration and ACE (I/D) polym orphism in 76 type 1 diabetic children and adolescents without diabetic nep hropathy (mean +/- SD: age 16 +/- 3 years; diabetes duration 7 +/- 4 years; age at diabetes onset 9 +/- 4 years; HbA(1c) 9.5 +/- 1.9%). Glomerular hyp erfiltration (defined as a glomerular filtration rate [GFR] greater than or equal to 135 ml . min(-1) . 1.73 m(-2) and by Cr-51-labeled EDTA plasma di sappearance technique) and ACE 1/D genotypes and plasma levels (enzyme-link ed immunosorbent assay [ELISA] method) were determined. RESULTS - Of the patients, 29 (38%) displayed glomerular hyperfiltration. A ll association between glomerular hyperfiltration and ACE (I/D) polymorphis m was observed (chi(2) = 7.09, P = 0.029) because of a reduced proportion o f DD genotypes among patients with glomerular hyperfiltration (4 vs. 19; ch i(2) = 6.03, P = 0.014) and not because of an excess of the II genotype (5 vs. 9: chi(2) = 0.04, P = 0.83). Age, diabetes duration, age at diabetes on set, and HbA(1c) were not different according to genotype. Patients with gl omerular hyperfiltration had low plasma ACE levels, compared with those wit h normal glomerular filtration (457 +/- 157 vs. 553 +/- 186 mu g/l; P = 0.0 27). CONCLUSIONS - These results suggest an unexpected association between glome rular hyperfiltration and ACE (I/D) polymorphism, characterized by a defect of the DD genotype among type 1 diabetic children and adolescents with glo merular hyperfiltration.