ADMA (asymmetric dimethylarginine), an endogenous inhibitor of nitric oxide synthase, is considered a major risk factor for cardiovascular disease and progression of renal disease. In the present study we aim to investigate the effect of acute variations in plasma glucose and insulin on plasma ADMA levels in young people with T1D (Type 1 diabetes). Fifteen young patients (ten males) with T1D, median age 18.3 (13.2–24.4) years, HbA1c (glycated haemoglobin) 9% (6.4–13.6%), underwent an overnight (18:00–08:00 hours) variable insulin infusion for euglycaemia, followed by a hyperinsulinaemic–euglycaemic clamp (08:00–12:00 hours). Blood samples were collected every 15 min for determination of ADMA, SDMA (symmetric dimethylarginine), valine, phenylalanine, arginine, creatinine and glucose. Insulin levels were assessed every 30 min. During the overnight period, glucose levels increased following the evening meal. In response to the protein intake there was a significant increase in ADMA, arginine, valine, phenylalanine and creatinine. For the remaining part of the night, glucose levels progressively decreased reaching 5 mmol/l by 04:00 hours. ADMA and SDMA did not change significantly. During the hyperinsulinaemic clamp, a significant fall in ADMA was observed, from 0.468±0.056 to 0.364±0.050 μmol/l (P<0.001). A significant fall was also found in SDMA, valine, phenylalanine, arginine and the ADMA/SDMA ratio (all P<0.001), but not in creatinine levels. No correlation was found between insulin sensitivity and ADMA. We conclude that acute changes in glycaemia do not significantly affect plasma ADMA levels whereas infusion of insulin significantly reduces ADMA, suggesting an important role for insulin in the regulation of this cardiovascular risk factor.
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December 2008
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Research Article|
November 12 2008
Effect of acute variations of insulin and glucose on plasma concentrations of asymmetric dimethylarginine in young people with Type 1 diabetes
M. Loredana Marcovecchio;
M. Loredana Marcovecchio
*Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, U.K.
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Barry Widmer;
Barry Widmer
*Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, U.K.
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David B. Dunger;
*Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, U.K.
Correspondence: Professor David B. Dunger (email [email protected]).
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R. Neil Dalton
R. Neil Dalton
†WellChild Laboratory, King's College London, Evelina Children's Hospital, Lambeth Palace Road, London SE1 7EH, U.K.
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Publisher: Portland Press Ltd
Received:
March 06 2008
Revision Received:
May 07 2008
Accepted:
May 22 2008
Accepted Manuscript online:
May 22 2008
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2008 Biochemical Society
2008
Clin Sci (Lond) (2008) 115 (12): 361–369.
Article history
Received:
March 06 2008
Revision Received:
May 07 2008
Accepted:
May 22 2008
Accepted Manuscript online:
May 22 2008
Citation
M. Loredana Marcovecchio, Barry Widmer, David B. Dunger, R. Neil Dalton; Effect of acute variations of insulin and glucose on plasma concentrations of asymmetric dimethylarginine in young people with Type 1 diabetes. Clin Sci (Lond) 1 December 2008; 115 (12): 361–369. doi: https://doi.org/10.1042/CS20080079
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