Uncomplicated type 1 diabetes is associated with increased asymmetric dimethylarginine concentrations

Context: Asymmetric dimethylarginine ( ADMA) has recently emerged as an independent risk marker for cardiovascular disease, but studies investigating the ADMA levels in type 1 diabetes mellitus ( DM) are scarce. Objective: We aimed to evaluate plasma ADMA, L-arginine concentrations, and L-arginine to ADMA ratio in uncomplicated type 1 diabetic patients and controls. Design and Subjects: Forty patients with type 1 DM who did not have clinical evidence of vascular complications and 35 healthy controls were included in the study. Results: Plasma ADMA concentrations were higher ( 2.6 +/- 1.9 vs. 1.7 +/- 0.7 mu mol/liter, P < 0.01), and L-arginine levels were lower ( 79.3 +/- 22.6 vs. 89.6 +/- 19.4 mu mol/liter, P < 0.05) in the diabetic group, compared with controls. The L-arginine to ADMA ratio was also lower in the diabetic group ( 38.7 +/- 17.1 vs. 62.0 +/- 27.9, P < 0.0001). In diabetic patients, logADMA correlated positively with body mass index ( BMI) ( P = 0.01), fasting blood glucose ( P = 0.006), and low-density lipoprotein cholesterol ( LDL-c) ( P = 0.01) and negatively with high-density lipoprotein cholesterol ( P = 0.03). L-Arginine to ADMA ratio correlated negatively with BMI ( P = 0.004), fasting blood glucose ( P = 0.02), and LDL-c ( P = 0.01) and positively with high- density lipoprotein cholesterol ( P = 0.04). In controls, logADMA and L-arginine to ADMA ratio correlated with BMI and LDL-c ( P < 0.05). In regression analysis, BMI predicted 15% variance of ADMA levels ( P = 0.02). Conclusions: We demonstrated that ADMA increases and L-arginine to ADMA ratio decreases, even before the development of vascular complications in type 1 DM.