Effect of ACE gene on diabetic nephropathy in NIDDM patients with insulin resistance

We investigated the influence of the angiotensin-converting enzyme (ACE) ge ne on the onset and/or progression of diabetic nephropathy in 62 Japanese p atients with non-insulin-dependent diabetes mellitis (NIDDM; type II diabet es). Because a number of factors are believed to be involved in the onset a nd/or progression of diabetic nephropathy, especially in patients with NIDD M, we selected the patients with well-matched risk factors, duration of dis ease, glycemic control, blood pressure, and others. All patients had normal renal function and none were receiving ACE inhibitors. Patients were divid ed into three groups according to albumin excretion rate (AER): group A, pa tients with an AER less than 15 mu g/min (n = 29); group B, patients with a n AER between 15 and 70 mu g/min (0 = 19); and group C, patients with an AE R greater than 70 mu g/min (n = 14), The glucose disposal rate was estimate d using a euglycemic hyperinsulinemic clamp. We determined the mean glucose disposal rate in 132 patients with NIDDM (6.49 mg/kg/min). Patients with a glucose disposal rate less than the mean rate were considered to have a hi gh degree of insulin resistance (n = 36). The presence of an insertion/dele tion (I/D) polymorphism of the ACE gene was determined by the polymerase ch ain reaction method. Among patients with a high degree of insulin resistanc e, diabetic nephropathy was present in 2 of 11 patients with the II genotyp e of the ACE gene compared with 19 of 25 patients with the ID or DD genotyp e (P = 0.0024). The prevalence of diabetic nephropathy was greater in patie nts with both significant insulin resistance and the D allele(19 of 25) tha n in the remaining patients (14 of 37; odds ratio, 5,20). These results sug gest that the ACE gene influences the onset and/or progression of diabetic nephropathy in patients with NIDDM with significant insulin resistance. (C) 1999 by the National Kidney Foundation, Inc.