Full Length Research Paper

Asymmetrical dimethylarginine (ADMA) and nitric oxide as potential cardiovascular risk factors in type 2 diabetes mellitus

Mohamed H. Mahfouz¹*, Ibrahim A. Emara¹, Mohamed S. Shouman² and Magda K. Ezz ³

¹ Biochemistry and ² Internal Medicine Departments,National Institute of Diabetes and Endocrinology

(NIDE), Cairo, Egypt.

³ Biochemistry Department, Faculty of Science. Ain Shams University.

*Corresponding author. E-mail: mhesham5@yahoo.com . Tel.: +202 24090447.  Fax: +202 24101382. 

Accepted 10 July, 2009

Abstract

Hyperglycemia affects biochemical parameters and influences the progression of coronary heart disease and mortality rates in diabetic patients. L-arginine is the substrate used by NO synthase to produce the vasodilator NO. However, in patients with type 2 diabetes mellitus (T2DM), there is an increase in serum levels of methylated L-arginines, such as ADMA, which is a recently identified potent cardiovascular risk factor. The aim of this study was designed to determine both risk factors (ADMA and NO) in type 2 diabetic patients with and without cardiovascular disease and to evaluate whether there is an association between ADMA and glycosylated hemoglobin (HbA1c) on the one hand and nitric oxide on the other hand. The study included 3 groups of subjects; Group I (Control group); comprising 20 healthy subjects; the mean age 48 ± 1.6 years; Group II: 20 diabetic patients without cardiovascular complications; the mean age 51.0 ± 1.96 years and Group III; 20 diabetic patients with evidence of cardiovascular complications; the mean age 54.0 ± 2.1 years. Fasting and postprandial serum glucose, HbA1c, lipid profile (total cholesterol, triacylglycerol, HDL-c and LDL-c), ADMA and serum NO metabolite level, were determined. Serum glucose (fasting and postprandial), HbA1c and ADMA levels showed significant increase in diabetic patients type 2 with and without cardiovascular complications compared to healthy normal control. Total cholesterol, triacylglycerol and LDL-c manifested significant elevations, while HDL-c level showed insignificant change in both groups in compared to non diabetic healthy subjects. Serum NO metabolite level was significantly reduced in the both diabetic patient groups compared with controls. No correlation between ADMA level and studied parameters in diabetic patients without evidence of cardiovascular complications, whereas in cardiovascular complications group, the ADMA level was positively correlated with both postprandial serum glucose and HbA1c, but there was a negative correlation between ADMA levels and NO. Also, NO was negatively correlated with postprandial serum glucose and HbA1c. In conclusion, ADMA and NO may serve as predictors for future cardiovascular events in type 2 diabetic patients. So, early diagnosis and good glycemic control are more effective in reducing the cardiovascular complications.

Key words:  Type 2 diabetes, cardiovascular disease, ADMA, nitric oxide.