Molecular detection of exercise-induced free radicals following ascorbate prophylaxis in type 1 diabetes mellitus: a randomised controlled trial

Aims/hypothesis Patients with type 1 diabetes mellitus are more susceptible than healthy individuals to exercise-induced oxidative stress and vascular endothelial dysfunction, which has important implications for the progression of disease. Thus, in the present study, we designed a randomised double...

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Veröffentlicht in:Diabetologia 2008-11, Vol.51 (11), p.2049-2059
Hauptverfasser: Davison, G. W, Ashton, T, George, L, Young, I. S, McEneny, J, Davies, B, Jackson, S. K, Peters, J. R, Bailey, D. M
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container_end_page 2059
container_issue 11
container_start_page 2049
container_title Diabetologia
container_volume 51
creator Davison, G. W
Ashton, T
George, L
Young, I. S
McEneny, J
Davies, B
Jackson, S. K
Peters, J. R
Bailey, D. M
description Aims/hypothesis Patients with type 1 diabetes mellitus are more susceptible than healthy individuals to exercise-induced oxidative stress and vascular endothelial dysfunction, which has important implications for the progression of disease. Thus, in the present study, we designed a randomised double-blind, placebo-controlled trial to test the original hypothesis that oral prophylaxis with vitamin C attenuates rest and exercise-induced free radical-mediated lipid peroxidation in type 1 diabetes mellitus. Methods All data were collected from hospitalised diabetic patients. The electron paramagnetic resonance spectroscopic detection of spin-trapped α-phenyl-tert-butylnitrone (PBN) adducts was combined with the use of supporting markers of lipid peroxidation and non-enzymatic antioxidants to assess exercise-induced oxidative stress in male patients with type 1 diabetes (HbA₁c 7.9 ± 1%, n = 12) and healthy controls (HbA₁c 4.6 ± 0.5%, n = 14). Following participant randomisation using numbers in a sealed envelope, venous blood samples were obtained at rest, after a maximal exercise challenge and before and 2 h after oral ingestion of 1 g ascorbate or placebo. Participants and lead investigators were blinded to the administration of either placebo or ascorbate treatments. Primary outcome was the difference in changes in free radicals following ascorbate ingestion. Results Six diabetic patients and seven healthy control participants were randomised to each of the placebo and ascorbate groups. Diabetic patients (n = 12) exhibited an elevated concentration of PBN adducts (p < 0.05 vs healthy, n = 14), which were confirmed as secondary, lipid-derived oxygen-centred alkoxyl (RO·) radicals (anitrogen = 1.37 mT and aβhydrogen = 0.18 mT). Lipid hydroperoxides were also selectively elevated and associated with a depression of retinol and lycopene (p < 0.05 vs healthy). Vitamin C supplementation increased plasma vitamin C concentration to a similar degree in both groups (p < 0.05 vs pre-supplementation) and attenuated the exercise-induced oxidative stress response (p < 0.05 vs healthy). There were no selective treatment differences between groups in the primary outcome variable. Conclusions/interpretation These findings are the first to suggest that oral vitamin C supplementation provides an effective prophylaxis against exercise-induced free radical-mediated lipid peroxidation in human diabetic blood. Clinical trials registration number: ISRCTN96164937 Funding: No externa
doi_str_mv 10.1007/s00125-008-1101-1
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W ; Ashton, T ; George, L ; Young, I. S ; McEneny, J ; Davies, B ; Jackson, S. K ; Peters, J. R ; Bailey, D. M</creator><creatorcontrib>Davison, G. W ; Ashton, T ; George, L ; Young, I. S ; McEneny, J ; Davies, B ; Jackson, S. K ; Peters, J. R ; Bailey, D. M</creatorcontrib><description>Aims/hypothesis Patients with type 1 diabetes mellitus are more susceptible than healthy individuals to exercise-induced oxidative stress and vascular endothelial dysfunction, which has important implications for the progression of disease. Thus, in the present study, we designed a randomised double-blind, placebo-controlled trial to test the original hypothesis that oral prophylaxis with vitamin C attenuates rest and exercise-induced free radical-mediated lipid peroxidation in type 1 diabetes mellitus. Methods All data were collected from hospitalised diabetic patients. The electron paramagnetic resonance spectroscopic detection of spin-trapped α-phenyl-tert-butylnitrone (PBN) adducts was combined with the use of supporting markers of lipid peroxidation and non-enzymatic antioxidants to assess exercise-induced oxidative stress in male patients with type 1 diabetes (HbA₁c 7.9 ± 1%, n = 12) and healthy controls (HbA₁c 4.6 ± 0.5%, n = 14). Following participant randomisation using numbers in a sealed envelope, venous blood samples were obtained at rest, after a maximal exercise challenge and before and 2 h after oral ingestion of 1 g ascorbate or placebo. Participants and lead investigators were blinded to the administration of either placebo or ascorbate treatments. Primary outcome was the difference in changes in free radicals following ascorbate ingestion. Results Six diabetic patients and seven healthy control participants were randomised to each of the placebo and ascorbate groups. Diabetic patients (n = 12) exhibited an elevated concentration of PBN adducts (p &lt; 0.05 vs healthy, n = 14), which were confirmed as secondary, lipid-derived oxygen-centred alkoxyl (RO·) radicals (anitrogen = 1.37 mT and aβhydrogen = 0.18 mT). Lipid hydroperoxides were also selectively elevated and associated with a depression of retinol and lycopene (p &lt; 0.05 vs healthy). Vitamin C supplementation increased plasma vitamin C concentration to a similar degree in both groups (p &lt; 0.05 vs pre-supplementation) and attenuated the exercise-induced oxidative stress response (p &lt; 0.05 vs healthy). There were no selective treatment differences between groups in the primary outcome variable. Conclusions/interpretation These findings are the first to suggest that oral vitamin C supplementation provides an effective prophylaxis against exercise-induced free radical-mediated lipid peroxidation in human diabetic blood. 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Target tissue resistance ; Exercise - physiology ; Free radicals ; Free Radicals - blood ; Free Radicals - metabolism ; glucose ; Glycated Hemoglobin A - metabolism ; Human Physiology ; Humans ; Hypoglycemic Agents - therapeutic use ; Hypotheses ; Insulin - therapeutic use ; Internal Medicine ; Lipid peroxidation ; Lipids ; Male ; Medical sciences ; Medicine ; Medicine &amp; Public Health ; Metabolic Diseases ; Oxidative stress ; Oxidative Stress - drug effects ; Patient Selection ; Reference Values ; Type 1 diabetes mellitus ; Vitamin C</subject><ispartof>Diabetologia, 2008-11, Vol.51 (11), p.2049-2059</ispartof><rights>Springer-Verlag 2008</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c497t-942c4238e4c634375894834d0b3e4bc5922bef1a775b91b13844b0a58407b6553</citedby><cites>FETCH-LOGICAL-c497t-942c4238e4c634375894834d0b3e4bc5922bef1a775b91b13844b0a58407b6553</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00125-008-1101-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-008-1101-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=20719832$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18769906$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Davison, G. W</creatorcontrib><creatorcontrib>Ashton, T</creatorcontrib><creatorcontrib>George, L</creatorcontrib><creatorcontrib>Young, I. S</creatorcontrib><creatorcontrib>McEneny, J</creatorcontrib><creatorcontrib>Davies, B</creatorcontrib><creatorcontrib>Jackson, S. K</creatorcontrib><creatorcontrib>Peters, J. R</creatorcontrib><creatorcontrib>Bailey, D. M</creatorcontrib><title>Molecular detection of exercise-induced free radicals following ascorbate prophylaxis in type 1 diabetes mellitus: a randomised controlled trial</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><description>Aims/hypothesis Patients with type 1 diabetes mellitus are more susceptible than healthy individuals to exercise-induced oxidative stress and vascular endothelial dysfunction, which has important implications for the progression of disease. Thus, in the present study, we designed a randomised double-blind, placebo-controlled trial to test the original hypothesis that oral prophylaxis with vitamin C attenuates rest and exercise-induced free radical-mediated lipid peroxidation in type 1 diabetes mellitus. Methods All data were collected from hospitalised diabetic patients. The electron paramagnetic resonance spectroscopic detection of spin-trapped α-phenyl-tert-butylnitrone (PBN) adducts was combined with the use of supporting markers of lipid peroxidation and non-enzymatic antioxidants to assess exercise-induced oxidative stress in male patients with type 1 diabetes (HbA₁c 7.9 ± 1%, n = 12) and healthy controls (HbA₁c 4.6 ± 0.5%, n = 14). Following participant randomisation using numbers in a sealed envelope, venous blood samples were obtained at rest, after a maximal exercise challenge and before and 2 h after oral ingestion of 1 g ascorbate or placebo. Participants and lead investigators were blinded to the administration of either placebo or ascorbate treatments. Primary outcome was the difference in changes in free radicals following ascorbate ingestion. Results Six diabetic patients and seven healthy control participants were randomised to each of the placebo and ascorbate groups. Diabetic patients (n = 12) exhibited an elevated concentration of PBN adducts (p &lt; 0.05 vs healthy, n = 14), which were confirmed as secondary, lipid-derived oxygen-centred alkoxyl (RO·) radicals (anitrogen = 1.37 mT and aβhydrogen = 0.18 mT). Lipid hydroperoxides were also selectively elevated and associated with a depression of retinol and lycopene (p &lt; 0.05 vs healthy). Vitamin C supplementation increased plasma vitamin C concentration to a similar degree in both groups (p &lt; 0.05 vs pre-supplementation) and attenuated the exercise-induced oxidative stress response (p &lt; 0.05 vs healthy). There were no selective treatment differences between groups in the primary outcome variable. Conclusions/interpretation These findings are the first to suggest that oral vitamin C supplementation provides an effective prophylaxis against exercise-induced free radical-mediated lipid peroxidation in human diabetic blood. Clinical trials registration number: ISRCTN96164937 Funding: No external funding.</description><subject>Acids</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Antioxidants</subject><subject>ascorbic acid</subject><subject>Ascorbic Acid - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Body Mass Index</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 1 - blood</subject><subject>Diabetes Mellitus, Type 1 - drug therapy</subject><subject>Diabetes. 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Thus, in the present study, we designed a randomised double-blind, placebo-controlled trial to test the original hypothesis that oral prophylaxis with vitamin C attenuates rest and exercise-induced free radical-mediated lipid peroxidation in type 1 diabetes mellitus. Methods All data were collected from hospitalised diabetic patients. The electron paramagnetic resonance spectroscopic detection of spin-trapped α-phenyl-tert-butylnitrone (PBN) adducts was combined with the use of supporting markers of lipid peroxidation and non-enzymatic antioxidants to assess exercise-induced oxidative stress in male patients with type 1 diabetes (HbA₁c 7.9 ± 1%, n = 12) and healthy controls (HbA₁c 4.6 ± 0.5%, n = 14). Following participant randomisation using numbers in a sealed envelope, venous blood samples were obtained at rest, after a maximal exercise challenge and before and 2 h after oral ingestion of 1 g ascorbate or placebo. Participants and lead investigators were blinded to the administration of either placebo or ascorbate treatments. Primary outcome was the difference in changes in free radicals following ascorbate ingestion. Results Six diabetic patients and seven healthy control participants were randomised to each of the placebo and ascorbate groups. Diabetic patients (n = 12) exhibited an elevated concentration of PBN adducts (p &lt; 0.05 vs healthy, n = 14), which were confirmed as secondary, lipid-derived oxygen-centred alkoxyl (RO·) radicals (anitrogen = 1.37 mT and aβhydrogen = 0.18 mT). Lipid hydroperoxides were also selectively elevated and associated with a depression of retinol and lycopene (p &lt; 0.05 vs healthy). Vitamin C supplementation increased plasma vitamin C concentration to a similar degree in both groups (p &lt; 0.05 vs pre-supplementation) and attenuated the exercise-induced oxidative stress response (p &lt; 0.05 vs healthy). There were no selective treatment differences between groups in the primary outcome variable. Conclusions/interpretation These findings are the first to suggest that oral vitamin C supplementation provides an effective prophylaxis against exercise-induced free radical-mediated lipid peroxidation in human diabetic blood. Clinical trials registration number: ISRCTN96164937 Funding: No external funding.</abstract><cop>Berlin/Heidelberg</cop><pub>Berlin/Heidelberg : Springer-Verlag</pub><pmid>18769906</pmid><doi>10.1007/s00125-008-1101-1</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; SpringerNature Journals
subjects Acids
Adolescent
Adult
Antioxidants
ascorbic acid
Ascorbic Acid - therapeutic use
Biological and medical sciences
Body Mass Index
Diabetes
Diabetes Mellitus, Type 1 - blood
Diabetes Mellitus, Type 1 - drug therapy
Diabetes. Impaired glucose tolerance
Disease prevention
Double-Blind Method
electron paramagnetic resonance spectroscopy
Electron Spin Resonance Spectroscopy
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Energy Metabolism
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Exercise - physiology
Free radicals
Free Radicals - blood
Free Radicals - metabolism
glucose
Glycated Hemoglobin A - metabolism
Human Physiology
Humans
Hypoglycemic Agents - therapeutic use
Hypotheses
Insulin - therapeutic use
Internal Medicine
Lipid peroxidation
Lipids
Male
Medical sciences
Medicine
Medicine & Public Health
Metabolic Diseases
Oxidative stress
Oxidative Stress - drug effects
Patient Selection
Reference Values
Type 1 diabetes mellitus
Vitamin C
title Molecular detection of exercise-induced free radicals following ascorbate prophylaxis in type 1 diabetes mellitus: a randomised controlled trial
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