Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Communication
  • Published:

Oxidative stress status in patients with diabetes mellitus: relationship to diet

Abstract

Objective: To investigate the relationship between dietary intakes and in vivo oxidative stress (OS) status in diabetic patients.

Design: Case–control study.

Setting: Outpatient-Clinic and Laboratory Endocrinology, University Antwerp.

Subjects and methods: A total of 30 patients (24 type 1 diabetes mellitus (T1DM)/6 type 2 diabetes mellitus (T2DM) were asked to complete a 2 weekdays+1weekend day food consumption questionnaire during the week preceding their yearly diabetes control consultation, when samples were collected for the assay of oxidative stress (OS) (blood levels of antioxidants, peroxides, malondialdehyde (MDA) and minerals). Blood samples were also collected from 25 age- and sex-matched healthy controls.

Results: Diabetic patients had lower glutathione (5.80±1.15 vs 6.75±1.03 μmol/g Hb in the controls, P=0.002) and higher MDA (0.687±0.212 vs 0.545±0.101 μmol/l, P=0.002). Although the group average intakes were within the Belgian RDA, intakes of fat >35% energy, fibre <15 g/1000 kcal, fruit <2 portions and vitamin E <10 mg/day were seen in more than 20 patients. Blood antioxidants did not correlate with intakes of energy, fat, protein or fibres or of their respective antioxidant. Vitamins A and E correlated with serum lipids (r=0.58, P <0.0005 between serum α-tocopherol and cholesterol). Blood peroxide levels were only related to intakes of saturated fat and cholesterol (P<0.05). In diabetic subjects but not in controls (P<0.05) MDA was related to glutathione and uric acid.

Conclusions: In diabetic patients, blood levels of antioxidants are not related to their dietary intakes but to serum lipids. Levels of oxidative damage products are only related to intakes of saturated fats and cholesterol and to levels of endogenous antioxidants.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  • Armstrong A, Chestnutt J & Young I (1996): The effect of dietary treatment on lipid peroxidation and antioxidant status in newly diagnosed non-insulin dependent diabetes. Free Radical Biol. Med. 21, 719–726.

    Article  CAS  Google Scholar 

  • Ascherio A, Stampfer MJ, Colditz GA, Rimm EB, Litin L & Willett WC (1992): Correlations of vitamin A and E intakes with the plasma concentrations of carotenoids and tocopherols among American men and women. J. Nutr. 122, 1792–1801.

    Article  CAS  Google Scholar 

  • Azzi A, Boscoboinik D, Marilley D, Ozer NK, Stauble B & Tasinato A (1995): Vitamin E: a sensor and an information transducer of the cell oxidation state. Am. J. Clin. Nutr. 62, 1337S–1346S.

    Article  CAS  Google Scholar 

  • BECEL (1995): In BECEL Voedingsprogramma versie 5.0, H van den Berg & Hartog-Union, The Netherlands.

  • Beutler E (1975): Reduced glutathione (GSH). In Red Cell Metabolism; A Manual of Biochemical Methods, ed. E Beutler, pp. 131–132. Orland FL: Grune & Stratton Inc.

    Google Scholar 

  • Blumberg JB (1995): Considerations of the scientific substantiation for antioxidant vitamins and beta-carotene in disease prevention. Am. J. Clin. Nutr. 62, 1521S–1526S.

    Article  CAS  Google Scholar 

  • Broekmans WM, Klopping-Ketelaars IA, Schuurman CR, Verhagen H, van den Berg H, Kok FJ & van Poppel G (2000): Fruits and vegetables increase plasma carotenoids and vitamins and decrease homocysteine in humans. J. Nutr. 130, 1578–1583.

    Article  CAS  Google Scholar 

  • Brownlee M (1994) Glycation and diabetic complications. Diabetes 43, 836–841.

    Article  CAS  Google Scholar 

  • Castenmiller JJ, Lauridsen ST, Dragsted LO, het Hof KH, Linssen JP & West CE (1999): Beta-carotene does not change markers of enzymatic and nonenzymatic antioxidant activity in human blood. J. Nutr. 129, 2162–2169.

    Article  CAS  Google Scholar 

  • Cao G, Booth SL, Sadowski JA & Prior RL (1998): Increases in human plasma antioxidant capacity after consumption of controlled diets high in fruit and vegetables. Am. J. Clin. Nutr. 68, 1081–1087.

    Article  CAS  Google Scholar 

  • Caye-Vaugien C, Krempf M, Lamarche P, Charbonnel B & Pieri J (1990): Determination of a-tocopherol in plasma, platelets and erythrocytes of type I and type II diabetic patients by HPLC. Int. J. Vitam. Nutr. Res. 60, 324–330.

    CAS  PubMed  Google Scholar 

  • Ceriello A (1997): Acute hyperglycaemia and oxidative stress generation. Diabetes Med 14, S45–S49.

    Article  Google Scholar 

  • Dandona P, Thusu K, Cook S & Nicotera T (1996): Oxidative damage to DNA in diabetes mellitus. Lancet 347, 444–445.

    Article  CAS  Google Scholar 

  • De Henauw S & De Backer G (1999): Nutrient and food intakes in selected subgroups of Belgian adults. Br. J. Nutr. 81, S37–S42.

    Article  Google Scholar 

  • de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J & Mamelle N (1999): Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation 99, 779–785.

    Article  CAS  Google Scholar 

  • Den Bulck M-Ch, Dufourny G, Guillaume M, Knops J, Maes L, Masson A, Mozin M, Reginster-Haneuse G & Vansant G (2000): Hoge Gezondsheidraad Voedingsaanbevelingen voor België. Ministerie Sociale Zaken, Volksgezondheid en Leefmilieu.

  • Devaraj S, Adams-Huet B, Fuller CJ & Jialal I (1997): Dose–response comparison of RRR-alpha-tocopherol and all-racemic alpha-tocopherol on LDL oxidation. Arterioscler. Thromb. Vasc. Biol. 17, 2273–2279.

    Article  CAS  Google Scholar 

  • Dimitrov N Meyer C & Gilliland D . (1991): Plasma tocopherol concentrations in response to supplemental vitamin E. Am. J. Clin Nutr. 53, 723–729.

    Article  CAS  Google Scholar 

  • Dormandy T (1983): An approach to free radicals. Lancet 2, 1010–1014.

    Article  CAS  Google Scholar 

  • Draper HH & Bettger WJ (1994): Role of nutrients in the cause and prevention of oxygen radical pathology. Adv. Exp. Med Biol. 366, 269–289.

    Article  CAS  Google Scholar 

  • El Sohemy A, Baylin A, Ascherio A, Kabagambe E, Spiegelman D & Campos H (2001): Population-based study of alpha- and gamma-tocopherol in plasma and adipose tissue as biomarkers of intake in Costa Rica. Am. J. Clin Nutr. 74, 356–363.

    Article  CAS  Google Scholar 

  • Engelen W, Manuel-y-Keenoy B, Vertommen J & De Leeuw I (2000): Effects of long-term supplementation with moderate pharmacologic doses of vitamin E are saturable and reversible in patients with type 1 diabetes. Am. J. Clin. Nutr. 72, 1142–1149.

    Article  CAS  Google Scholar 

  • Enstrom JE, Kanim LE & Klein MA (1992): Vitamin C intake and mortality among a sample of the United States population. Epidemiology 3, 194–202.

    Article  CAS  Google Scholar 

  • European Diabetes Policy Group (1998): In European Guidelines for Diabetes Care. A Desktop Guide to Type 1 (Insulin-dependent) Diabetes Mellitus, ed P Home, Speyer, Germany: Alter Wirtz Druck & Verlag.

  • Friedewald WT, Levy M & Frederickson DS (1972): Estimation of the concentration of low density lipoprotein cholesterol in plasma without the use of the preparative ultracentrifuge. Clin. Chem. 18, 499–502.

    CAS  Google Scholar 

  • Gale CR, Ashurst HE, Powers HJ & Martyn CN (2001): Antioxidant vitamin status and carotid atherosclerosis in the elderly. Am. J. Clin. Nutr. 74, 402–408.

    Article  CAS  Google Scholar 

  • Gey KF, Brubacher GB & Stahelin HB (1987): Plasma levels of antioxidant vitamins in relation to ischemic heart disease and cancer. Am. J. Clin. Nutr. 45, 1368–1377.

    Article  CAS  Google Scholar 

  • Gey KF, Moser UK, Jordan P, Stahelin HB, Eichholzer M & Ludin E (1993): Increased risk of cardiovascular disease at suboptimal plasma concentrations of essential antioxidants: an epidemiological update with special attention to carotene and vitamin C. Am. J. Clin. Nutr. 57, 787S–797S.

    Article  CAS  Google Scholar 

  • Gey KF, Puska P, Jordan P & Moser UK (1991): Inverse correlation between plasma vitamin E and mortality from ischemic heart disease in cross-cultural epidemiology. Am. J. Clin. Nutr. 53, 326S–334S.

    Article  CAS  Google Scholar 

  • Gidden F & Shenkin A (2000): Laboratory support of the clinical nutrition service. Clin. Chem. Lab. Med. 38, 693–714.

    Article  CAS  Google Scholar 

  • GISSI (1999): Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet 354, 447–455.

  • Griesmacher A, Kindhauser M, Andert SE, Schreiner W, Toma C, Knoebl P, Pietschmann P, Prager R, Schnack C, Schernthaner G & Mueller MM (1995): Enhanced serum levels of thiobarbituric-acid-reactive substances in diabetes mellitus. Am. J. Med. 98, 469–475.

    Article  CAS  Google Scholar 

  • Hall ND, Blake DR & Bacon PA (1982): Serum sulphydryl levels in early synovitis. J. Rheumatol. 9, 593–596.

    CAS  PubMed  Google Scholar 

  • Hebert JR, Hurley TG, Hsieh J, Rogers E, Stoddard AM, Sorensen G & Nicolosi RJ (1994): Determinants of plasma vitamins and lipids: the Working Well Study. Am. J. Epidemiol. 140, 132–147.

    Article  CAS  Google Scholar 

  • Hegsted DM (1992): Point of view defining a nutritious diet: need for new dietary standards. J. Am. Coll. Nutr. 11, 241–245.

    Article  CAS  Google Scholar 

  • Hertog MGL, Hollman PCH & Katan MB (1992): Content of potentially anticarcinogenic flavonoids of 28 vegetables and 9 fruits commonly consumed in The Netherlands. J. Agric. Food Chem. 40, 2379–2383.

    Article  CAS  Google Scholar 

  • Hertog MGL, Hollman PC & van de Putte B (1993): Content of potentially anticarcinogenic flavonoids of tea infusions, wines, and fruit juices. J. Agric. Food Chem. 41, 1242–1246.

    Article  CAS  Google Scholar 

  • Heseker H & Schneider R (1994): Requirement and supply of vitamin C, E and beta-carotene for elderly men and women. Eur. J. Clin. Nutr. 48, 118–127.

    CAS  PubMed  Google Scholar 

  • Hininger IA, Meyer-Wenger A, Moser U, Wright A, Southon S, Thurnham D, Chopra M, van den Berg H, Olmedilla B, Favier AE & Roussel AM (2001): No significant effects of lutein, lycopene or beta-carotene supplementation on biological markers of oxidative stress and LDL oxidizability in healthy adult subjects. J. Am. Coll. Nutr. 20, 232–238.

    Article  CAS  Google Scholar 

  • Hiramatsu K & Arimori S (1988): Increased superoxide production by mononuclear cells of patients with hypertriglyceridemia and diabetes. Diabetes 37, 832–837.

    Article  CAS  Google Scholar 

  • Hjermann I, Velve BK, Holme I & Leren P (1981): Effect of diet and smoking intervention on the incidence of coronary heart disease. Report from the Oslo Study Group of a randomised trial in healthy men. Lancet 2, 1303–1310.

    Article  CAS  Google Scholar 

  • Holland B, Welch AA, Unwin ID, Buss DH, Pau AA & Southgate DAT (1998): The Composition of Foods. In The Composition of Foods: Tables Based on Data of the Royal Society of Chemistry and Ministry of Agriculture, Fisheries and Food, eds EM Widdowson & RA McCance. Trowbridge, Wiltshire: Redwood Books.

    Google Scholar 

  • Hu FB, Rimm EB, Stampfer MJ, Ascherio A, Spiegelman D & Willett WC (2000): Prospective study of major dietary patterns and risk of coronary heart disease in men. Am. J. Clin. Nutr. 72, 912–921.

    Article  CAS  Google Scholar 

  • Hunt J, Smith C & Wolff S (1990): Autoxidative glycosylation and possible involvement of peroxides and free radicals in LSL modification by glucose. Diabetes 39, 1420–1424.

    Article  CAS  Google Scholar 

  • Jain SK, Levine SN, Duett J & Hollier B (1991): Reduced vitamin E and increased lipofuscin products in erythrocytes of diabetic rats. Diabetes 40, 1241–1244.

    Article  CAS  Google Scholar 

  • Jandak J, Steiner M & Richardson PD (1989): Alfa-tocopherol, an effective inhibitor of platelet adhesion. Blood 73, 141–149.

    CAS  PubMed  Google Scholar 

  • Jukes TH (1992): Historical perspective: antioxidants, nutrition and evolution. Prev. Med. 21, 270–276.

    Article  CAS  Google Scholar 

  • Kannel W & McGee D (1979): Diabetes and glucose tolerance as risk factors for cardiovascular disease: The Framingham Study. Diabetes Care 2, 120–126.

    Article  CAS  Google Scholar 

  • Kardinaal AF, van' Veer P, Brants HA, van den Berg H, van Schoonhoven J & Hermus RJ (1995): Relations between antioxidant vitamins in adipose tissue, plasma, and diet. Am. J. Epidemiol. 141, 440–450.

    Article  CAS  Google Scholar 

  • Lissi E, Salim-Hanna M, Pascual C & del Castillo MD (1995): Evaluation of total antioxidant potential (TRAP) and total antioxidant reactivity from luminol-enhanced chemiluminescence measurements. Free Radical Biol. Med. 18, 153–158.

    Article  CAS  Google Scholar 

  • Maxwell SR, Thomason H, Sandler D, LeGuen C, Baxter MA, Thorpe GH, Jones AF & Barnett AH (1997): Poor glycaemic control is associated with reduced serum free radical scavenging (antioxidant) activity in non-insulin-dependent diabetes mellitus. Ann. Clin. Biochem. 34, 638–644.

    Article  Google Scholar 

  • Mullarkey C, Edelstein D & Brownlee M (1990): Free radical generation by early glycation products: a mechanism for accelerated atherogenesis in diabetes. Biochem. Biophys. Res. Comm. 173, 932–939.

    Article  CAS  Google Scholar 

  • Murakami K, Kondo T & Kawakami Y (1989): Impairment of glutathione metabolism in erythrocytes from patients with diabetes mellitus. Metabolism 38, 753–758.

    Article  CAS  Google Scholar 

  • NEVO (1998): In Nevotabel 1996: herwerkte versie 1998, eds LJM van der Heyden, KFAM Hulshof, JAE Languis, HM Van Oosten, JC Pruissen-Boskaljon & P Van Stratum. Zeist, The Netherlands: Krips Repro Meppel.

  • Nielsen F, Mikkelsen BB, Nielsen JB, Andersen HR & Grandjean P (1997): Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors. Clin. Chem. 43, 1209–1214.

    CAS  PubMed  Google Scholar 

  • NUBEL (1995): Belgische voedingsmiddelentabel, Ministry of Public Health, Brussels, Belgium.

  • Paolisso G (2000): Chronic vitamin E administration improves brachial reactivity and increases intracellular magnesium concentration in type 2 diabetic patients. J. Clin. Endocr Metab. 85, 109–115.

    Article  CAS  Google Scholar 

  • Prieme H, Loft S, Nyyssonen K, Salonen JT & Poulsen HE (1997): No effect of supplementation with vitamin E, ascorbic acid, or coenzyme Q10 on oxidative DNA damage estimated by 8-oxo-7,8-dihydro-2'- deoxyguanosine excretion in smokers. Am. J. Clin. Nutr. 65, 503–507.

    Article  CAS  Google Scholar 

  • Rathmann W, Hauner H, Dannehl K & Gries FA (1993): Association of elevated serum uric acid with coronary heart disease in diabetes mellitus. Diabetes Metab. 19, 159–166.

    CAS  Google Scholar 

  • Riedl J, Linseisen J, Hoffmann J & Wolfram G (1999): Some dietary fibers reduce the absorption of carotenoids in women. J. Nutr. 129, 2170–2176.

    Article  CAS  Google Scholar 

  • Riemersma RA, Wood DA, Macintyre CCA, Elton RA, Gey FK & Oliver MF (1991): Risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene. Lancet 337, 1–5.

    Article  CAS  Google Scholar 

  • Ross R (1993): The pathogenesis of atherosclerosis: a perspective for the 1990's. Nature 362, 801–809.

    Article  CAS  Google Scholar 

  • Sempos CT, Johnson NE, Smith EL & Gilligan C (1985): Effects of intra-individual and inter-individual variation in repeated dietary records. Am. J. Epidemiol. 121, 120–130.

    Article  CAS  Google Scholar 

  • Sies H (1991): Oxidative stress: from basic research to clinical application. Am. J. Med. 91, 31S–38S.

    Article  CAS  Google Scholar 

  • Simons LA, Von Konigsmark M & Balasubramaniam S (1996): What dose of vitamin E is required to reduce susceptibility of LDL to oxidation? Aust NZ J Med. 26, 496–503.

    Article  CAS  Google Scholar 

  • Sinclair AJ, Girling AJ, Gray L, Le Guen C & Lunec J (1991): Disturbed handling of ascorbic acid in diabetic patients with and without microangiopathy during high dose ascorbate supplementation. Diabetologia 34, 171–175.

    Article  CAS  Google Scholar 

  • Stampfer MJ, Hennekens CH, Manson JAE, Colditz Graham A, Rosner B, Willett WC (1993): Vitamin E consumption and the risk of coronary disease in women. N. Engl. J. Med. 328, 1444–1449.

    Article  CAS  Google Scholar 

  • Stephens N, Parsons A & Mitchinson MJ (1996): Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 347, 781–786.

    Article  CAS  Google Scholar 

  • Tangney CC, Shekelle RB & Raynor W (1987): Intra-and interindividual variation in measurements of beta-carotene, retinol, and tocopherols in diet and plasma. Am. J. Clin. Nutr. 45, 764–769.

    Article  CAS  Google Scholar 

  • Thornalley P, McLellan A & Sönksen P (1996): Negative association between erythrocyte reduced glutathione concentration and diabetic complications. Clin. Sci. 91, 575–582.

    Article  CAS  Google Scholar 

  • Tsai EC, Hirsch IB, Brunzell JD & Chait A (1994): Reduced plasma peroxyl radical trapping capacity and increased susceptibility of LDL to oxidation in poorly controlled IDDM. Diabetes 43, 1010–1014.

    Article  CAS  Google Scholar 

  • van den Berg R, van Vliet T, Broekmans WM, Cnubben NH, Vaes WH, Roza L, Haenen GR, Bast A & van den Berg H (2001): A vegetable/fruit concentrate with high antioxidant capacity has no effect on biomarkers of antioxidant status in male smokers. J. Nutr. 131, 1714–1722.

    Article  CAS  Google Scholar 

  • Verhagen H, Poulsen HE, Loft S, van Poppel G, Willems MI & van Bladeren PJ (1995): Reduction of oxidative DNA-damage in humans by Brussels sprouts. Carcinogenesis 16, 969–970.

    Article  CAS  Google Scholar 

  • Willett WC, Stampfer MJ, Underwood BA, Speizer FE, Rosner B & Hennekens CH (1983): Validation of a dietary questionnaire with plasma carotenoid and alpha- tocopherol levels. Am. J. Clin. Nutr. 38, 631–639.

    Article  CAS  Google Scholar 

  • Yusuf S, Dagenais G, Pogue J, Bosch J & Sleight P (2000): Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N. Engl. J. Med. 342, 154–160.

    Article  CAS  Google Scholar 

  • Zino S, Skeaff M, Williams S & Mann J (1997): Randomised controlled trial of effect of fruit and vegetable consumption on plasma concentrations of lipids and antioxidants. Brit. Med. J 314, 1787–1791.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the patients and control subjects who participated in the study, and S Schrans, P Aerts, M Vinckx from the Laboratory of Endocrinology and E Biebaut from the Department of Biology for skilful technical assistance.

Author information

Authors and Affiliations

Authors

Contributions

Guarantors: I De Leeuw and B Manuel-y-Keenoy

Contributors: ND and CvG selected the patients and collected and calculated dietary intakes. JV, GyH and JvdV recruited healthy controls and were responsible for the biochemical assays. IDL was the group leader. BMK directed the study, analysed the data and wrote the manuscript

Corresponding author

Correspondence to B Manuel-y-Keenoy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dierckx, N., Horvath, G., van Gils, C. et al. Oxidative stress status in patients with diabetes mellitus: relationship to diet. Eur J Clin Nutr 57, 999–1008 (2003). https://doi.org/10.1038/sj.ejcn.1601635

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ejcn.1601635

Keywords

Search

Quick links