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Uncomplicated Type 1 Diabetes Is Associated with Increased Asymmetric Dimethylarginine Concentrations

Departments of Endocrinology and Metabolism (A.E.A., M.Ar., M.Ak., F.B.T.) and Medical Biochemistry (A.S.-D., N.A.), Gazi University Faculty of Medicine, 06550 Ankara, Turkey

Address all correspondence and requests for reprints to: Alev E. Altinova, Ahmet Rasim Sok. 41/6, 06550 Çankaya, Ankara, Turkey. E-mail: alevaltinova{at}yahoo.com.

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 µmol/liter, P < 0.01), and L-arginine levels were lower (79.3 ± 22.6 vs. 89.6 ± 19.4 µmol/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.

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