Zur Bedeutung ausgewählter Vitamine (B-Vitamine, Vitamin C, Vitamin E) bei Patienten mit Typ-2-Diabetes

Zusammenfassung

Bei Patienten mit Typ-2-Diabetes besteht ein deutlich erhöhtes Morbiditäts- und Letalitätsrisiko. Bei der Erforschung pathophysiologischer Zusammenhänge des Diabetes ist die Rolle des oxidativen Stresses in den Vordergrund gerückt. Mikronährstoffe sind in vielfältiger Weise in diese komplexen Prozesse eingebunden. Ein Mangel oder Überschuss an Mikronährstoffen kann zu Verschiebungen im anti- bzw. prooxidativen Gleichgewicht beitragen und zur Progression sekundärer Komplikationen des Diabetes führen. Einige Vitamine sind von besonderer präventiver Wirkung. Ein enger Zusammenhang besteht zwischen den B-Vitaminen Folat, Vitamin B₂, Vitamin B₆, Vitamin B₁₂ und Homozystein, einem kardiovaskulären Risikofaktor sowie zwischen Thiamin und diabetischer Neuropathie. Die Antioxidanzien Vitamin C und Vitamin E spielen v. a. bei der Lipidperoxidation eine Rolle und schützen Zellmembranen und Lipoproteine. Vitamin C wirkt darüber hinaus positiv im Polyolstoffwechsel. Die Ernährungsempfehlungen für Typ-2-Diabetiker entsprechen weitestgehend denen von Stoffwechselgesunden. Um eine ausreichende Zufuhr von Antioxidanzien zu gewährleisten, wird diesen Patienten vor allem empfohlen, die Aufnahme von Obst und Gemüse auf mindestens 5 Portionen pro Tag zu erhöhen. Für eine generelle Supplementierung mit Mikronährstoffen besteht derzeit keine Notwendigkeit. In Einzelfällen, d. h. wenn eine adäquate Aufnahme über die Nahrung nicht erreicht wird, kann eine ergänzende Zufuhr von Mikronährstoffen empfehlenswert sein. Diabetiker sollten insbesondere auf eine ausreichende Versorgung mit B-Vitaminen und Antioxidanzien achten, um das Risiko für kardiovaskuläre Erkrankungen und diabetische Spätfolgen zu senken.

Abstract

It has been shown that patients with type 2-diabetes have a high risk for morbidity and lethality. During the last years, research on the pathophysiology of diabetes has focused on the role of oxidative stress. Micronutrients are involved in these complex processes in different ways (protection, scavening effect, compound of key enzymes). A deficiency or an excess of micronutrients may contribute to a shift in the anti- or pro-oxidative balance and may enhance the progression of secondary diabetic complications. Some vitamins have special benefical preventive effects. A close relationship has been found between the B-vitamins folate, vitamin B₂, vitamin B₆, vitamin B₁₂ and homocysteine, a cardiovascular risk factor as well as for thiamine and diabetic neuropathy. The antioxidants vitamin C and vitamin E mainly play a role in lipid peroxidation being important for the protection of cell membranes and lipoproteins. Vitamin C in addition has favourable effects in the polyol pathway. Nutritional recommendations for diabetic patients mainly correspond to those of healthy people. To ensure a sufficient intake of antioxidants, diabetic patients are advised to increase consumption of fruits and vegetables to more than 5 portions per day. In general, additional intake of micronutrients does not seem to be necessary. However, individual cases may profit from micronutrient supplementation when adequate intake from foods can not be achieved. Diabetics should in particular focuse on a full supply with B-vitamins and antioxidants to reduce their risk for cardiovascular diseases and diabetic complications.

Typ-2-Diabetes - antioxidative Vitamine - B-Vitamine - Supplementierung - Prävention

Type 2-diabetes - antioxidative vitamins - B-vitamins - supplementation - prevention

Literatur

• 1 Hauner H, Köster I, Ferber L von. Prävalenz des Diabetes mellitus in Deutschland 1998 - 2001.  Dtsch Med Wochenschr. 2003;  128 2632-2638
• 2 Bundesärztekammer, Arzneimittelkommission der deutschen Ärzteschaft, Deutsche Diabetes Gesellschaft, Fachkommission Diabetes Sachsen, Deutsche Gesellschaft für Innere Medizin, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften .Nationale Versorgungs-Leitlinie Diabetes mellitus Typ 2. Nationales Programm für Versorgungs-Leitlinien der Bundesärztekammer 2002; 1. Auflage Mai 2002. (korrigierte Version vom 1.4.2003) 1-23
• 3 European Arterial Risk Policy Group . A strategy for arterial risk assessment and management in type 2 non-insulin-dependent) diabetes mellitus. European Arterial Risk Policy Group on behalf of the International Diabetes Federation European Region.  Diabet Med. 1997;  14 611-621
• 4 Opara E C. Oxidative stress, micronutrients, diabetes mellitus and its complications.  J R Soc Health. 2002;  122 28-34
• 5 Thompson K H, Godin D V. Micronutrients and antioxidants in the progression of diabetes.  Nutr Res. 1995;  15 1377-1410
• 6 American-Diabetes-Association . American Diabetes Association: clinical practice recommendations.  Diabetes Care. 1997;  20 S1-S70
• 7 Nutrition Guidelines Committee of the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes . Recommendations for the nutritional management of patients with diabetes mellitus.  Eur J Clin Nutr. 2000;  54 353-355
• 8 Maxwell S R. Coronary artery disease - free radical damage, antioxidant protection and the role of homocysteine.  Basic Res Cardiol. 2000;  95 I65-I71
• 9 Yeromenko Y, Lavie L, Levy Y. Homocysteine and cardiovascular risk in patients with diabetes mellitus.  Nutr Metab Cardiovasc Dis. 2001;  11 108-116
• 10 Buysschaert M, Dramais A S, Wallemacq P E, Hermans M P. Hyperhomocysteinemia in type 2 diabetes: relationship to macroangiopathy, nephropathy, and insulin resistance.  Diabetes Care. 2000;  23 1816-1822
• 11 Hultberg B, Agardh E, Andersson A, Brattstrom L, Isaksson A, Israelsson B, Agardh C D. Increased levels of plasma homocysteine are associated with nephropathy, but not severe retinopathy in type 1 diabetes mellitus.  Scand J Clin Lab Invest. 1991;  51 277-282
• 12 Straub R H, Rokitzki L, Schumacher T, Hillman C, Palitzsch K-H, Schölmerich J. No evidence of deficiency of vitamin A, E, β-carotene, B₁, B₂, B₆, B₁₂ and folate in neuropathic type II diabetic women.  Int J Vit Nutr Res. 1993;  63 239-240
• 13 Stabler S P, Estacio R, Jeffers B W, Cohen J A, Allen R H, Schrier R W. Total homocysteine is associated with nephropathy in non-insulin-dependent diabetes mellitus.  Metabolism. 1999;  48 1096-1101
• 14 Hoogeveen E K, Kostense P J, Jager A, Heine R J, Jakobs C, Bouter L M, Donker A J, Stehouwer C D. Serum homocysteine level and protein intake are related to risk of microalbuminuria: the Hoorn Study.  Kidney Int. 1998a;  54 203-209
• 15 Hoogeveen E K, Kostense P J, Jakobs C, Dekker J M, Nijpels G, Heine R J, Bouter L M, Stehouwer C D. Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes: 5-year follow-up of the Hoorn Study.  Circulation. 2000b;  101 1506-1511
• 16 Aarsand A K, Carlsen S M. Folate administration reduces circulating homocysteine levels in NIDDM patients on long-term metformin treatment.  J Intern Med. 1998;  244 169-174
• 17 Baliga B S, Reynolds T, Fink L M, Fonseca V A. Hyperhomocysteinemia in type 2 diabetes mellitus: cardiovascular risk factors and effect of treatment with folic acid and pyridoxine.  Endocr Pract. 2000;  6 435-441
• 18 Child D F, Hudson P R, Jones H, Davies G K, De P, Mukherjee S, Brain A M, Williams C P, Harvey J N. The effect of oral folic acid on glutathione, glycaemia and lipids in type 2 diabetes.  Diab Nutr Metab. 2004;  17 95-102
• 19 Etten R W van, Koning E J de, Verhaar M C, Gaillard C A, Rabelink T J. Impaired NO-dependent vasodilation in patients with Type II (non-insulin-dependent) diabetes mellitus is restored by acute administration of folate.  Diabetologia. 2002;  45 1004-1010
• 20 Chait A, Malinow M R, Nevin D N, Morris C D, Eastgard R L, Kris-Etherton P, Pi-Sunyer F X, Oparil S, Resnick L M, Stern J S, Haynes R B, Hatton D C, Metz J A, Clark S, McMahon M, Holcomb S, Reusser M E, Snyder G W, McCarron D A. Increased dietary micronutrients decrease serum homocysteine concentrations in patients at high risk of cardiovascular disease.  Am J Clin Nutr. 1999;  70 881-887
• 21 The-Homocysteine-Studies-Collaboration . Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis.  JAMA. 2002;  288 2015-2022
• 22 McNulty H, Dowey L C, Scott J M, Molloy A M, McAnena L B, Hughes J P, Ward M, Strain J J. Riboflavin supplementation lowers plasma homocysteine in individuals homozygous for the MTHFR C677T polymorphism.  J Inherit Metab Dis. 2003;  26 12
• 23 Thornalley P J. Glycation in diabetic neuropathy: characteristics, consequences, causes, and therapeutic options.  Int Rev Neurobiol. 2002;  50 37-57
• 24 Babaei-Jadidi R, Karachalias N, Ahmed N, Battah S, Thornalley P J. Prevention of incipient diabetic nephropathy by high-dose thiamine as benfotiamine.  Diabetes. 2003;  52 2110-2120
• 25 Bitsch R. Zur Biokinetik von Vitamin B1-(Thiamin-)Präparaten. In: Federlin K (Hrsg) Polyneuropathien. Stuttgart; Thieme Verlag 1995: 18-22
• 26 Stracke H, Lindemann A, Federlin K. A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy.  Exp Clin Endocrinol Diabetes. 1996;  104 311-316
• 27 Winkler G, Pal B, Nagybeganyi E, Ory I, Porochnavec M, Kempler P. Effectiveness of different benfotiamine dosage regimens in the treatment of painful diabetic neuropathy.  Arzneimittelforschung. 1999;  49 220-224
• 28 Hunt J V. Acorbic acid and diabetes mellitus.  Subcellular Biochemistry. 1996;  25 369-405
• 29 Cunningham J J, Mearkle P L, Brown R G. Vitamin C: an aldose reductase inhibitor that normalizes erythrocyte sorbitol in insulin-dependent diabetes mellitus.  J Am Coll Nutr. 1994 a;  13 344-350
• 30 Will J C, Byers T. Does diabetes melllitus increase the requirement for vitamin C?.  Nutrition Reviews. 1996;  54 193-202
• 31 Sinclair A J, Girling A J, Gray L, Lunec J, Barnett A H. An investigation of the relationship between free radical activity and vitamin C metabolism in elderly diabetic subjects with retinopathy.  Gerontology. 1992;  38 268-274
• 32 Vinson J A, Staretz M E, Bose P, Kassm H M, Basalyga B S. In vitro and in vivo reduction of erythrocyte sorbitol by ascorbic acid.  Diabetes. 1989;  38 1036-1041
• 33 Wang H, Zhang Z B, Wen R R, Chen J W. Experimental and clinical studies on the reduction of erythrocyte sorbitol-glucose ratios by ascorbic acid in diabetes mellitus.  Diabetes Res Clin Pract. 1995;  28 1-8
• 34 Paolisso G, Balbi V, Volpe C, Varricchio G, Gambardella A, Saccomanno F, Ammendola S, Varricchio M, D'Onofrio F. Metabolic benefits deriving from chronic vitamin C supplementation in aged non-insulin dependent diabetics.  J Am Coll Nutr. 1995;  14 387-392
• 35 Davie S J, Gould B J, Yudkin J S. Effect of vitamin C on glycosylation of proteins.  Diabetes. 1992;  41 167-173
• 36 Ting H H, Timimi F K, Boles K S, Creager S J, Ganz P, Creager M A. Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus.  J Clin Invest. 1996;  97 22-28
• 37 Sinclair A J, Girling A J, Gray L, Guen C Le, Lunec J, Barnett A H. Disturbed handling of ascorbic acid in diabetic patients with and without microangiopathy during high dose ascorbate supplementation.  Diabetologia. 1991;  34 171-175
• 38 Darko D, Dornhorst A, Kelly F J, Ritter J M, Chowienczyk P J. Lack of effect of oral vitamin C on blood pressure, oxidative stress adn endothelial function in type II diabetes.  Clinical Science. 2002;  103 339-344
• 39 Roesen P, Toeller M. Vitamin E in diabetes. Increased oxidative stress and its prevention as a strategy to prevent vascular complications?.  Int J Vitam Nutr Res. 1999;  69 206-212
• 40 Jandak J, Steiner M, Richardson P D. Alpha-tocopherol, an effective inhibitor of platelet adhesion.  Blood. 1989;  73 141-149
• 41 Polidori M C, Mecocci P, Stahl W, Parente B, Cecchetti R, Cherubini A, Cao P, Sies H, Senin U. Plasma levels of lipophilic antioxidants in very old patients with type 2 diabetes.  Diabetes Metab Res Rev. 2000;  16 15-19
• 42 Toeller M, Klischan A, Heitkamp G, Schumacher W, Milne R, Buyken A, Karamanos B, Gries F A. Nutritional intake of 2868 IDDM patients from 30 centres in Europe. EURODIAB IDDM Complications Study Group.  Diabetologia. 1996;  39 929-939
• 43 Davi G, Ciabattoni G, Consoli A, Mezzetti A, Falco A, Santarone S, Pennese E, Vitacolonna E, Bucciarelli T, Costantini F, Capani F, Patrono C. In vivo formation of 8-iso-prostaglandin f2alpha and platelet activation in diabetes mellitus: effects of improved metabolic control and vitamin E supplementation.  Circulation. 1999;  99 224-229
• 44 Salonen J T, Nyyssonen K, Tuomainen T P, Maenpaa P H, Korpela H, Kaplan G A, Lynch J, Helmrich S P, Salonen R. Increased risk of non-insulin dependent diabetes mellitus at low plasma vitamin E concentrations: a four year follow up study in men.  BMJ. 1995;  311 1124-1127
• 45 Deutsche Gesellschaft für Ernährung e. V. .Referenzwerte für die Nährstoffzufuhr. first ed. Umschau. Frankfurt am Main; Braus 2000
• 46 Mayer-Davis E J, Costacou T, King I, Zaccaro D J, Bell R A. Plasma and dietary vitamin E in relation to incidence of type 2 diabetes. The Insulin Resistance and Atherosclerosis Study (IRAS).  Diabetes Care. 2002;  25 2172-2177
• 47 Millen A E, Gruber M, Klein R, Klein B E, Palta M, Mares J A. Relations of serum ascorbic acid and alpha-tocopherol to diabetic retinopathy in the Third National Health and Nutrition Examination Survey.  Am J Epidemiol. 2003;  158 225-233
• 48 Millen A E, Klein R, Folsom A R, Stevens J, Palta M, Mares J A. Relation between intake of vitamins C and E and risk of diabetic retinopathy in the Atherosclerosis Risk in Communities Study.  Am J Clin Nutr. 2004;  79 865-873
• 49 Fuller C J, Chandalia M, Garg A, Grundy S M, Jialal I. RRR-alpha-tocopheryl acetate supplementation at pharmacologic doses decreases low-density-lipoprotein oxidative susceptibility but not protein glycation in patients with diabetes mellitus.  Am J Clin Nutr. 1996;  63 753-759
• 50 Jain S K, McVie R, Jaramillo J J, Palmer M, Smith T, Meachum Z D, Little R L. The effect of modest vitamin E supplementation on lipid peroxidation products and other cardiovascular risk factors in diabetic patients.  Lipids. 1996a;  31 S87-90
• 51 Jain S K, Krueger K S, McVie R, Jaramillo J J, Palmer M, Smith T. Relationship of blood thromboxane-B2 (TxB2) with lipid peroxides and effect of vitamin E and placebo supplementation on TxB2 and lipid peroxide levels in type 1 diabetic patients.  Diabetes Care. 1998;  21 1511-1516
• 52 Upritchard J E, Sutherland W H, Mann J I. Effect of supplementation with tomato juice, vitamin E, and vitamin C on LDL oxidation and products of inflammatory activity in type 2 diabetes.  Diabetes Care. 2000;  23 733-738
• 53 Devaraj S, Jialal I. Alpha tocopherol supplementation decreases serum C-reactive protein and monocyte interleukin-6 levels in normal volunteers and type 2 diabetic patients.  Free Radic Biol Med. 2000;  29 790-792
• 54 Lonn E, Yusuf S, Hoogwerf B, Pogue J, Yi Q, Zinman B, Bosch J, Dagenais G, Mann J F, Gerstein H C. Effects of vitamin E on cardiovascular and microvascular outcomes in high-risk patients with diabetes: results of the HOPE study and MICRO-HOPE substudy.  Diabetes Care. 2002;  25 1919-1927
• 55 Bowry V W, Ingold K U, Stocker R. Vitamin E in human low-density lipoprotein. When and how this antioxidant becomes pro-oxidant.  Biochem J. 1992;  288 341-44
• 56 Gaede P, Poulsen H E, Parving H H, Pedersen O. Double-blind, randomised study of the effect of combined treatment with vitamin C and E on albuminuria in type 2 diabetic patients.  Diabet Med. 2001;  18 756-760
• 57 Beckman J A, Goldfine A B, Gordon M B, Garrett L A, Keaney Jr J F, Creager M A. Oral antioxidant therapy improves endothelial function in type 1 but not type 2 diabetes mellitus.  Am J Physiol Heart Circ Physiol. 2003;  285 H2392-2398
• 58 Peponis V, Papathanasiou M, Kapranou A, Magkou C, Tyligada A, Melidonis A, Drosos T, Sitaras N M. Protective role of oral antioxidant supplementation in ocula surface of diabetic patients.  Br J Ophthalmol. 2002;  86 1369-1373
• 59 Farvid M S, Jalali M, Siassi F, Saadat N, Hosseini M. The impact of vitamins and/or mineral supplementation on blood pressure in type 2 diabetes.  J Am Coll Nutr. 2004;  23 272-279
• 60 Deutsche Gesellschaft für Ernährung . Vitaminversorgung in Deutschland - Stellungnahme der Deutschen Gesellschaft für Ernährung.  EU. 2004;  51 51-55
• 61 Bree A de, Dusseldorp M van, Brouwer I A, Hof K H van het, Steegers-Theunissen R P. Folate intake in Europe: recommended, actual and desired intake.  Eur J Clin Nutr. 1997;  51 643-660
• 62 Stanger O, Herrmann W, Pietrzik K, Fowler B, Geisel J, Dierkes J, Weger M. DACH-Liga Homocystein e. V. . Konsensuspapier der D.A.C.H.-Liga Homocystein über den rationellen klinischen Umgang mit Homocystein und B-Vitaminen bei kardiovaskulären wie thrombotischen Erkrankungen - Richtlinien und Empfehlungen.  Clin Chem Lab Med. 2003;  41 1392-1403
• 63 O'Connell B S. Select vitamins and minerals in the management of diabetes.  Diabetes Spectrum. 2001;  14 133-148
• 64 Cunningham J J, Ellis S L, McVeigh K L, Levine R E, Calles-Escandon J. Reduced mononuclear leukocyte ascorbic acid content in adults with insulin-dependent diabetes mellitus consuming adequate dietary vitamin C.  Metabolism. 1991;  40 146-149
• 65 Mooradian A D, Morley J E. Micronutrient status in diabetes mellitus.  Am J Clin Nutr. 1987;  45 877-895
• 66 Hunt J V, Bottoms M A, Mitchinson M J. Ascorbic acid oxidation: a potential cause of the elevated severity of atherosclerosis in diabetes mellitus?.  FEBS Lett. 1992;  311 161-164
• 67 Yoshida H, Ishikawa T, Nakamura H. Vitamin E/lipid peroxide ratio and susceptibility of LDL to oxidative modification in non-insulin-dependent diabetes mellitus.  Arterioscler Thromb Vasc Biol. 1997;  17 1438-1446
• 68 Engelen W, Keenoy B M, Vertommen J, Leeuw I De. 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. 2000;  72 1142-1149