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 micromol/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) microg/l, p = 0.027; 44.2 (32.6-60.9) vs. 33.1 (22.4-51.0) microg/l; p = 0.003 and 70.8 (33.3-85.5) vs 46.3 (23.9-76.8) microg/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.
Sibal
Latika
L
Newcastle University, Newcastle upon Tyne, UK. latikasibal@hotmail.com
Agarwal
Sharad C
SC
Schwedhelm
Edzard
E
Lüneburg
Nicole
N
Böger
Rainer H
RH
Home
Philip D
PD
D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000502:physiology; D012307:Risk Factors; D014463:Ultrasonography; D014664:Vasodilation; D055815:Young Adult
D015415:Biomarkers; D015815:Cell Adhesion Molecules; C018524:N,N-dimethylarginine; D001120:Arginine; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III