Plasma concentrations of asymmetric-dimethyl-arginine in type 2 diabetes associate with glycemic control and glomerular filtration rate but not with risk factors of vasculopathy

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS). Increased plasma levels of ADMA may indicate endothelial dysfunction and increased risk of angiopathy. The relation of ADMA to diabetes, glycemic control, and renal function, especially early diabetic hyperfiltration, remains unknown. We tried to evaluate whether there is an association between ADMA and glycosylated hemoglobin (GHbA(1c)) on the one hand and glomerular filtration rate (GFR) on the other hand in diabetic subjects with normal or slightly increased GFR. We also studied whether plasma ADMA is associated with some risk factors of vasculopathy (hypercholesterolemia and hypertension). The study subjects consisted of 86 patients with type 2 diabetes and 65 control subjects. Plasma ADMA levels were measured by high-pressure liquid chromatography as o-pthalaldehyde (OPA) derivatives and GFR was determined by the plasma clearance of chromium 51-EDTA. The diabetic patients had lower plasma ADMA levels than the nondiabetic control subjects (0.29 +/- 0.15 v 0.34 +/- 0.16 pmol/L, P < .03). In the diabetic subjects, plasma ADMA concentrations were inversely correlated with GHbA(1c) (R = -0.28, P = .01). In a multivariate linear model, significant predictors of ADMA were GFR (R = -0.32, P = .008) in diabetic subjects and GHbA(1c), (R = -0.19, P = .03) and GFR (R = -0.19, P = .02) in all subjects. Plasma ADMA was not associated with risk factors of vasculopathy. We conclude that diabetic patients with a normal or slightly increased GFR have lower circulating ADMA concentrations than nondiabetic control subjects. In type 2 diabetic patients high GFR and poor glycemic control were related to low plasma ADMA concentrations. Copyright 2003, Elsevier Science (USA). All rights reserved.