A study of endothelial function and circulating asymmetric dimethylarginine levels in people with Type 1 diabetes without macrovascular disease or microalbuminuria

Background: Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of endothelial nitric oxide synthase (eNOS) that is associated with endothelial dysfunction, and is a risk marker for cardiovascular disease, a significant problem in Type 1 diabetes. The aim of the present study was to measure circulating ADMA, and define its association with endothelial dysfunction and endothelial markers in people with Type 1 diabetes with low likelihood of macrovascular disease. Methods: Sixty-one young people with Type 1 diabetes without macrovascular disease or nephropathy and 62 healthy volunteers underwent brachial artery flow-mediated dilatation (FMD) and assay of plasma ADMA and adhesion molecules. Results: Age, gender, BMI, lipid profile and renal function were similar in the two groups. People with Type 1 diabetes had impaired FMD compared to healthy controls (5.0+/-0.4 vs 8.9+/-0.4 %; p<0.001). Plasma ADMA levels were significantly lower in the people with diabetes compared to healthy controls (0.52+/-0.12 vs 0.66+/-0.20 umol/l, p<0.001). Plasma ICAM-1, E-selectin and PAI-1 levels were significantly higher in people with diabetes compared to healthy controls (median 201 (IQR 172-226) vs 180 (156-216) ug/l, p=0.027; 44.2 (32.6-60.9) vs. 33.1 (22.4-51.0) ug/l; p=0.003 and 70.8 (33.3-85.5) vs 46.3 (23.9-76.8) ug/l, p=0.035). Plasma ADMA and VCAM-1 levels were positively correlated (r=0.37, p=0.003) in people with diabetes. There was no correlation between the plasma ADMA and FMD. Conclusions: ADMA levels are not associated with endothelial dysfunction in young adults with Type 1 diabetes without microalbuminuria or known macrovascular disease. This suggests that the impaired endothelial function in these individuals is not a result of eNOS inhibition by ADMA.