Asymmetric dimethylarginine as a risk factor for cardiovascular disease in Japanese patients with type 2 diabetes mellitus

Aims Although asymmetric dimethylarginine (ADMA) is known to be involved in the developing process of cardiovascular diseases (CVD), little is known about the effects of ADMA on atherosclerosis in Asian patients with diabetes , who have the racial feature of lower body mass index (BMI) and decreased capacity of insulin secretion and sensitivity. Methods We employed 55 Japanese patients with type 2 diabetes mellitus (mean age, 64·2 years; 56% men) in a 6‐month‐longitudinal study and 450 patients (mean age, 62·7 years; 56% men) in a cross‐sectional study and examined the association of serum ADMA with atherosclerosis parameters [intima‐media thickness (IMT) and brachial‐ankle pulse wave velocity (baPWV)] as well as with the presence of CVD. Results In the longitudinal study, multiple regression analysis showed that basal serum ADMA level had a significantly positive association with changes in IMT (β = 0·35, P = 0·03) independently of age, duration of diabetes, BMI, blood pressure, low‐density lipoprotein and high‐density lipoprotein (LDL and HDL) cholesterol, HbA_1c, and renal function. In the cross‐sectional study, the serum ADMA level was significantly and positively associated with the presence of CVD (odds ratio = 7·22, 95% confidence interval 1·29–40·40, P = 0·02, by logistic analysis) and with baPWV (β = 0·14, P < 0·01, by multiple regression analysis). In contrast, serum symmetric dimethylarginine level, a structural isomer of ADMA, was associated neither with parameters for atherosclerosis nor with the presence of CVD in both studies. Conclusions Serum ADMA is a predictor of atherosclerosis and associated with the presence of CVD in Japanese patients with type 2 diabetes mellitus.