Oxidative stress in patients with type 1 diabetes mellitus: is it affected by a single bout of prolonged exercise?

Maria Pia Francescato, Giuliana Stel, Mario Geat, Sabina Cauci, Maria Pia Francescato, Giuliana Stel, Mario Geat, Sabina Cauci

Abstract

Presently, no clear-cut guidelines are available to suggest the more appropriate physical activity for patients with type 1 diabetes mellitus due to paucity of experimental data obtained under patients' usual life conditions. Accordingly, we explored the oxidative stress levels associated with a prolonged moderate intensity, but fatiguing, exercise performed under usual therapy in patients with type 1 diabetes mellitus and matched healthy controls. Eight patients (4 men, 4 women; 49±11 years; Body Mass Index 25.0±3.2 kg·m(-2); HbA1c 57±10 mmol·mol(-1)) and 14 controls (8 men, 6 women; 47±11 years; Body Mass Index 24.3±3.3 kg·m(-2)) performed a 3-h walk at 30% of their heart rate reserve. Venous blood samples were obtained before and at the end of the exercise for clinical chemistry analysis and antioxidant capacity. Capillary blood samples were taken at the start and thereafter every 30 min to determine lipid peroxidation. Patients showed higher oxidative stress values as compared to controls (95.9±9.7 vs. 74.1±12.2 mg·L(-1) H2O2; p<0.001). In both groups, oxidative stress remained constant throughout the exercise (p = NS), while oxidative defence increased significantly at the end of exercise (p<0.02) from 1.16±0.13 to 1.19±0.10 mmol·L(-1) Trolox in patients and from 1.09±0.21 to 1.22±0.14 mmol·L(-1) Trolox in controls, without any significant difference between the two groups. Oxidative stress was positively correlated to HbA1c (p<0.005) and negatively related with uric acid (p<0.005). In conclusion, we were the first to evaluate the oxidative stress in patients with type 1 diabetes exercising under their usual life conditions (i.e. usual therapy and diet). Specifically, we found that the oxidative stress was not exacerbated due to a single bout of prolonged moderate intensity aerobic exercise, a condition simulating several outdoor leisure time physical activities. Oxidative defence increased in both patients and controls, suggesting beneficial effects of prolonged aerobic fatiguing exercise.

Conflict of interest statement

Competing Interests: Part of this study was funded by unconditional financial support from Bayer Italia S.p.A. (Italy). There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Figure 1. Glycemia and insulin concentration before…
Figure 1. Glycemia and insulin concentration before and at the end of the 3-h exercises.
Panel A. Glycemia (mmol·L−1) was significantly higher in patients both before and at the end of the exercise (p<0.01) and decreased significantly in patients with type 1 DM at the end of the trial (p<0.05). Panel B. Insulin concentration (pmol·L−1) was significantly higher in patients both before and at the end of the exercise (p<0.001) and decreased significantly in both groups at the end of the trial (p<0.005). In both panels: shaded boxes = patients, open boxes = healthy control subjects.
Figure 2. Oxidative stress values throughout the…
Figure 2. Oxidative stress values throughout the 3-h exercises.
Oxidative stress was significantly higher in patients (p

Figure 3. Relationship between oxidative stress and…

Figure 3. Relationship between oxidative stress and HbA 1c or uric acid.

Panel A. Relationship between…

Figure 3. Relationship between oxidative stress and HbA1c or uric acid.
Panel A. Relationship between baseline HbA1c values (mmol·mol−1) and oxidative stress (mg·L−1 H2O2). The relationship is statistically significant (n = 20, R = 0.649, p<0.005). Panel B. Relationship between baseline uric acid values (mg·dL−1) and oxidative stress (mg·L−1 H2O2). The relationship is statistically significant (n = 22, R = 0.621, p<0.005). In both panels: full dots = patients with type 1 DM, open dots = healthy control subjects, dotted lines = 95% confidence limits.
Figure 3. Relationship between oxidative stress and…
Figure 3. Relationship between oxidative stress and HbA1c or uric acid.
Panel A. Relationship between baseline HbA1c values (mmol·mol−1) and oxidative stress (mg·L−1 H2O2). The relationship is statistically significant (n = 20, R = 0.649, p<0.005). Panel B. Relationship between baseline uric acid values (mg·dL−1) and oxidative stress (mg·L−1 H2O2). The relationship is statistically significant (n = 22, R = 0.621, p<0.005). In both panels: full dots = patients with type 1 DM, open dots = healthy control subjects, dotted lines = 95% confidence limits.

References

    1. Powers SK, Nelson WB, Hudson MB (2011) Exercise-induced oxidative stress in humans: Cause and consequences. Free Radic Biol Med 51: 942–950.
    1. Pavlatou MG, Papastamataki M, Apostolakou F, Papassotiriou I, Tentolouris N (2009) FORT and FORD: two simple and rapid assays in the evaluation of oxidative stress in patients with type 2 diabetes mellitus. Metabolism 58: 1657–1662.
    1. Bashan N, Kovsan J, Kachko I, Ovadia H, Rudich A (2009) Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species. Physiol Rev 89: 27–71.
    1. West IC (2000) Radicals and oxidative stress in diabetes. Diabet Med 17: 171–180.
    1. Drews G, Krippeit-Drews P, Dufer M (2010) Oxidative stress and beta-cell dysfunction. Pflugers Arch 460: 703–718.
    1. Vollaard NBJ, Shearman JP, Cooper CE (2005) Exercise-Induced Oxidative Stress: Myths, Realities and Physiological Relevance. Sports Med 35: 1045–1062.
    1. VanderJagt DJ, Harrison JM, Ratliff DM, Hunsaker LA, Vander Jagt DL (2001) Oxidative stress indices in IDDM subjects with and without long-term diabetic complications. Clin Biochem 34: 265–270.
    1. Golbidi S, Badran M, Laher I (2012) Antioxidant and Anti-Inflammatory Effects of Exercise in Diabetic Patients. Exp Diabetes Res 2012: 941868.
    1. Marra G, Cotroneo P, Pitocco D, Manto A, Di Leo MAS, et al. (2002) Early Increase of Oxidative Stress and Reduced Antioxidant Defenses in Patients With Uncomplicated Type 1 Diabetes: A case for gender difference. Diabetes Care 25: 370–375.
    1. Laaksonen DE, Atalay M, Niskanen L, Uusitupa M, Hanninen O, et al. (1996) Increased Resting and Exercise-Induced Oxidative Stress in Young IDDM Men. Diabetes Care 19: 569–574.
    1. Domìnguez C, Ruiz E, Gussinye M, Carrascosa A (1998) Oxidative Stress at Onset and in Early Stages of Type 1 Diabetes in Children and Adolescents. Diabetes Care 21: 1736–1742.
    1. Reis JS, Veloso CA, Volpe CM, Fernandes JS, Borges EA, et al. (2012) Soluble RAGE and malondialdehyde in type 1 diabetes patients without chronic complications during the course of the disease. Diab Vasc Dis Res 9: 309–314.
    1. Vessby J, Basu S, Mohsen R, Berne C, Vessby B (2002) Oxidative stress and antioxidant status in type 1 diabetes mellitus. J Intern Med 251: 69–76.
    1. American Diabetes Association (2004) Physical activity/exercise and diabetes. Diabetes Care 27: S58–S62.
    1. Chimen M, Kennedy A, Nirantharakumar K, Pang T, Andrews R, et al. (2012) What are the health benefits of physical activity in type 1 diabetes mellitus? A literature review. Diabetologia 55: 542–551.
    1. Davison GW, George L, Jackson SK, Young IS, Davies B, et al. (2002) Exercise, free radicals, and lipid peroxidation in type 1 diabetes mellitus. Free Radic Biol Med 33: 1543–1551.
    1. Garelnabi MO, Brown WV, Le NA (2008) Evaluation of a novel colorimetric assay for free oxygen radicals as marker of oxidative stress. Clin Biochem 41: 1250–1254.
    1. Sharma A, Kharb S, Chugh SN, Kakkar R, Singh GP (2000) Evaluation of oxidative stress before and after control of glycemia and after vitamin E supplementation in diabetic patients. Metabolism 49: 160–162.
    1. Berg TJ, Nourooz-Zadeh J, Wolff SP, Tritschler HJ, Bangstad H-J, et al. (1998) Hydroperoxides in Plasma Are Reduced by Intensified Insulin Treatment: A randomized controlled study of IDDM patients with microalbuminuria. Diabetes Care 21: 1295–1300.
    1. Francescato MP, Carrato S (2011) Management of Exercise-induced Glycemic Imbalances in Type 1 Diabetes. Curr Diabetes Rev 7: 253–263.
    1. Francescato MP, Geat M, Accardo A, Blokar M, Cattin L, et al. (2011) Exercise and Glycemic Imbalances: a Situation-Specific Estimate of Glucose Supplement. Med Sci Sports Exerc 43: 2–11.
    1. Tamborlane WV (2007) Triple Jeopardy: Nocturnal Hypoglycemia after Exercise in the Young with Diabetes. J Clin Endocrinol Metab 92: 815–816.
    1. Owen WE, Roberts WL (2004) Cross-Reactivity of Three Recombinant Insulin Analogs with Five Commercial Insulin Immunoassays. Clin Chem 50: 257–259.
    1. Kamhieh-Milz J, Salama A (2014) Oxidative Stress Is Predominant in Female but Not in Male Patients with Autoimmune Thrombocytopenia. Oxid Med Cell Longev 2014: 9.
    1. Abramson JL, Hooper WC, Jones DP, Ashfaqc S, Rhodes SD, et al. (2005) Association between novel oxidative stress markers and C-reactive protein among adults without clinical coronary heart disease. Atherosclerosis 178: 115–121.
    1. De Cosmo S, Lamacchia O, Rauseo A, Viti R, Gesualdo L, et al. (2006) Cigarette Smoking Is Associated With Low Glomerular Filtration Rate in Male Patients With Type 2 Diabetes. Diabetes Care 29: 2467–2470.
    1. Mantovani G, Madeddu C, Macciò A, Gramignano G, Lusso MR, et al. (2004) Cancer-Related Anorexia/Cachexia Syndrome and Oxidative Stress: An Innovative Approach beyond Current Treatment. Cancer Epidemiol Biomarkers Prev 13: 1651–1659.
    1. Powers SK, Jackson MJ (2008) Exercise-Induced Oxidative Stress: Cellular Mechanisms and Impact on Muscle Force Production. Physiol Rev 88: 1243–1276.
    1. Takahashi M, Miyashita M, Kawanishi N, Park J, Hayashida H, et al. (2013) Low-volume exercise training attenuates oxidative stress and neutrophils activation in older adults. Eur J Appl Physiol 113: 1117–1126.
    1. Gomez-Cabrera M-C, Domenech E, Viña J (2008) Moderate exercise is an antioxidant: Upregulation of antioxidant genes by training. Free Radic Biol Med 44: 126–131.
    1. Viña J, Sanchis-Gomar F, Martinez-Bello V, Gomez-Cabrera M (2012) Exercise acts as a drug; the pharmacological benefits of exercise. Br J Pharmacol 167: 1–12.
    1. Grimm JJ, Ybarra J, Berné C, Muchnick S, Golay A (2004) A new table for prevention of hypoglycaemia during physical activity in type 1 diabetic patients. Diabetes Metab 30: 465–470.
    1. Geat M, Stel G, Poser S, Driussi C, Stenner E, et al. (2013) Whole-body glucose oxidation rate during prolonged exercise in type 1 diabetic patients under usual life conditions. Metabolism 62: 836–844.
    1. Jenni S, Oetliker C, Allemann S, Ith M, Tappy L, et al. (2008) Fuel metabolism during exercise in euglycaemia and hyperglycaemia in patients with type 1 diabetes mellitus—a prospective single-blinded randomised crossover trial. Diabetologia 51: 1457–1465.
    1. Stettler C, Jenni S, Allemann S, Steiner R, Hoppeler H, et al. (2006) Exercise capacity in subjects with type 1 diabetes mellitus in eu- and hyperglycaemia. Diabetes Metab Res Rev 22: 300–306.
    1. Chokkalingam K, TzinTzas K, Norton L, Jewell K, Macdonald IA, et al. (2007) Exercise under hyperinsulinaemic conditions increases whole-body glucose disposal without affecting glycogen utilisation in type 1 diabetes. Diabetologia 50: 414–421.
    1. Goodarzi MT, Navidi AA, Rezaei M, Babahmadi-Rezaei H (2010) Oxidative damage to DNA and lipids: correlation with protein glycation in patients with type 1 diabetes. J Clin Lab Anal 24: 72–76.
    1. Menon V, Ram M, Dorn J, Armstrong D, Muti P, et al. (2004) Oxidative stress and glucose levels in a population-based sample. Diabet Med 21: 1346–1352.
    1. Lippi G, Montagnana M, Franchini M, Favaloro EJ, Targher G (2008) The paradoxical relationship between serum uric acid and cardiovascular disease. Clin Chim Acta 392: 1–7.
    1. Ames BN, Cathcart R, Schwiers E, Hochstein P (1981) Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci 78: 6858–6862.
    1. Peluso I, Morabito G, Urban L, Ioannone F, Serafini M (2012) Oxidative stress in atherosclerosis development: the central role of LDL and oxidative burst. Endocr Metab Immune Disord Drug Targets 12: 351–360.
    1. Di Santolo M, Banfi G, Stel G, Cauci S (2009) Association of recreational physical activity with homocysteine, folate and lipid markers in young women. Eur J Appl Physiol 105: 111–118.

Source: PubMed

3
Sottoscrivi