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Abstract
In patients with type 2 diabetes, oxidative stress could be increased by their metabolic changes. Elevated plasma homocysteine is considered as one of markers of enhanced oxidative stress. Due to oxidative stress, some complications like cardiovascular or renal diseases may develop in type 2 diabetes patients. Plasma homocysteine concentration may be increased if folate status were inadequate. Protective effects against oxidative stress may be diminished if the status of anti-oxidative nutrient as vitamin C was poor. It is, therefore, important to maintain adequate status of folate and vitamin C in type 2 diabetes patients. Thus, this study was performed to determine the effects of supplementation of folate and/or ascorbate on blood glycated hemoglobin (HbA1c) level, serum concentrations of homocysteine and cholesterol, plasma oxidized low density-lipoprotein (LDL), concentration and plasma glutathione peroxidase (GSH-Px) activity in the patients with type 2 diabetes. A total of 92 type 2 diabetes patients participated voluntarily with written consents. They were divided into one of the four experimental groups; Control (C), Folate-supplemented (F), Ascorbate-supplemented (A), and Folate plus ascorbate-supplemented (FA). The subjects in C were taken placebo, those in F were supplemented 1 mg of folate, those in A received 1,000 mg of ascorbate, and those in FA were given 1 mg of folate plus 1,000 mg of ascorbate daily for 4 weeks. Supplementation of folate or ascorbate resulted to increase serum folate level or plasma ascorbate concentration apparently, respectively. Folate supplementation not ascorbate seemed to decrease plasma concentrations of homocysteine and oxidized LDL and reduce plasma GSH-Px activity. There might not be synergic effect of the supplementation of folate plus ascorbate. The results indicate that oxidative stress in the patients with type 2 diabetes may lower mainly by folate supplementation.
Figures and Tables
Table 3
Nutrient intakes of the subjects
Values are Mean ± SD.
Values with asterisks are significantly different between male and female within each group by Student t-test: *p < 0.05, **p < 0.01, ***p < 0.001.
C: control, F: folate-supplemented, A: ascorbate-supplemented, FA: folate plus ascorbate-supplemented, EAR: estimated average requirement
Table 4
Plasma concentrations of folate and ascorbate of the subjects before and after supplementation for 4 weeks
Values are Mean ± SD.
Values with asterisks are significantly different between male and female within each group by Student t-test: *p < 0.05, **p < 0.01, ***p < 0.001.
Values with different large superscripts are significantly different between 0 and 4 week at p < 0.05 by paired test.
C: control, F: folate-supplemented, A: ascorbate-supplemented, FA: folate plus ascorbate-supplemented
Table 5
Blood HbA1C and plasma Hcy concentrations of the subjects before and after supplementation for 4 weeks
Values are Mean ± SD.
Values with asterisks are significantly different between male and female within each group by Student t-test: *p < 0.05, **p < 0.01, ***p < 0.001.
Values with different small superscripts are significantly different between the four groups at p < 0.05 by Tukey's test.
Values with different large superscripts are significantly different between 0 and 4 week at p < 0.05 by paired test.
C: control, F: folate-supplemented, A: ascorbate-supplemented, FA: folate plus ascorbate-supplemented, FBG: fasting blood glucose, HbA1c: glycated hemoglobin, Hcy: homocysteine
Table 6
Concentrations of serum T-C, LDL-C and plasma oxidized LDL and glutathione peroxidase activity of the subjects before and after supplementation for 4 weeks
Values are Mean ± SD.
Values with asterisks are significantly different between male and female within each group by Student t-test: *p < 0.05, **p < 0.01, ***p < 0.001.
Values with different large superscripts are significantly different between 0 and 4 week at p < 0.05 by paired test.
C: control, F: folate-supplemented, A: ascorbate-supplemented, FA: folate plus ascorbate-supplemented, LDL: low density lipoprotein, T-C: total-cholesterol, LDL-C: low density lipoprotein-cholesterol, GSH-Px: glutathione peroxidase
References
1. Stevens MJ, Feldman EL, Greene DA. The etiology of diabetic neuropathy: The combined roles of metabolic and vascular defect. Diabetic Med. 1995. 12(7):1566–1579.
2. Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Cardiovascular risk factors clustering with endogenous hyperinsulinemia predict death from coronary heart disease in patients with Type II diabetes. Diabetologia. 2000. 43(2):148–155.
3. Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998. 339(4):229–234.
4. McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol. 1969. 56(1):111–128.
5. Moghadasion MH, McManus BM, Frohlich JJ. Homocysteine and coronary heart disease; clinical evidence and genetic and metabolic background. Arch Intern Med. 1997. 157(20):2299–2308.
6. van Guldener C, Stehouwer CD. Hyperhomocysteinemia, vascular pathology, and endothelial dysfunction. Semin Thromb Hemost. 2000. 26(3):281–289.
7. McCully KS. Chemical pathology of homocysteine I. Atherogenesis. Ann Clin Lab Sci. 1993. 23(6):477–493.
8. Aukrus P, Berge RK, Muller F, Ueland PM, Svardal AM, Froland SS. Elevated plasma levels of reduced homocysteine in common variable immunodeficiency-a marker of enhanced oxidative stress. Eur J Clin Invest. 1997. 27(10):723–730.
9. Blom HJ, Kleinveld HA, Boers GH, Demacker PN, Hak-Lemmers HL, Te Poele-Pothoff MT, Trijbels JM. Lipid peroxidation and susceptibility of low-density lipoprotein to in vitro oxidation in hyperhomocysteinemia. Eur J Clin Invest. 1995. 25(3):149–154.
10. Paolisso G, D'Amore A, Giugliano D, Cereillo A, Varricchio M, D'Onofrio F. Pharmacological doses of vitamin E improve insulin action in healthy subjects and non-insulin dependent diabetic patients. Am J Clin Nutr. 1993. 57(5):650–656.
11. Yoshida H, Ishikawa T, Nakamura H. Vitamin E/lipid peroxide ratio and susceptibility of LDL to oxidative modification in NIDDM. Arterioscler Throm Vasc Biol. 1997. 17(7):1438–1446.
12. Al-Obaidi MK, Stubbs PJ, Collinson P, Conroy R, Graham I, Noble MI. Elevated homocysteine levels are associated with increased ischemic myocardial injury in acute coronary syndromes. J Am Coll Cardiol. 2000. 36(4):1217–1222.
13. Medina MA, Amores-Snchez MI. Homocysteine: an emergent cardiovascular risk factor? Eur J Clin Invest. 2000. 30(9):754–762.
14. Nygard O, Refsum H, Ueland PM, Vollset SE. Major lifestyle determinants of plasma total homocysteine distribution: The Hordaland Homocysteine Study. Am J Clin Nutr. 1998. 67(2):263–270.
15. Ubbink JB, van der Merwe A, Delport R, Allen RH, Stabler SP, Riezler R, Vermaak WJ. The effect of a subnormal vitamin B6 status on homocysteine metabolism. J Clin Invest. 1996. 98(1):177–184.
16. Davie SJ, Gould BJ, Yudkin JS. Effect of Vitamin C on glycosylation of protein. Diabetes. 192. 41(2):167–173.
17. Sies H, Stahl W. Vitamin E and vitamin C and carotenoid as antioxidants. Am J Clin Nutr. 1995. 62(6):1315s–1321s.
18. Rinkins LE. Effects of alloxan diabetes on rat river ascorbic acid. Horm Metab Res. 1981. 13(2):123–129.
19. Som S, Basu S, Mukherjee D, Deb S, Choudhury PR, Mukherjee S. Ascorbic acid metabolism in diabetes mellitus. Metabolism. 1981. 30(6):572–577.
20. Chang NS, Kim JM, Park SW, Cho YW, Kwon OO. Folate intake and plasma homocysteine levels in the elderly patients with NIDDM. Korean J Nutr. 2000. 33(3):250–256.
21. Seo HY, Ha AW, Cho JS. The dietary intake, plasma lipid peroxidation and vitamin C in NIDDM patients. Korean J Nutr. 2001. 34(8):912–919.
22. Hwang MR, Shin MH, Rhee JA, Kweon SS, Lim HS. Effects of folic acid or ascorbate supplemendation on plasma homocysteine levels and oxidative stress in Korean adults with impared fasting glucose. Korean J Community Nutrition. 2008. 13(2):263–275.
23. Okamura M. An improved method for determination of L-ascorbic acid and L-dehydroascorbic acid in blood plasma. Clin Chem Acta. 1980. 103(3):259–268.
24. Lim HS. Folate status in pregnant and lactating women. J Korean Soc Food Sci Nutr. 1997. 26(5):983–992.
25. Ha AW, Kim HM. The study of lipid-peroxidation, antioxidant enzymes, and the antioxidant vitamin in NIDDM patients with microvascular-diabetic complications. Korean J Nutr. 1999. 32(1):17–23.
26. Dipolack AT. Safety of antioxidation vitamins and beta-carotene. Am J Clin Nutr. 1995. 62(6):1510s–1516s.
27. Park HS, Lee YM. Effects of vitamin C supplementation on blood sugar and antioxidative status in type 2 diabetes mellitus patients. J Korean Acad Nurs. 2003. 33(2):170–178.
28. Fonseca VA, Stone A, Munshi M, Baliga BS, Aljada A, Thusu K, Fink L, Candona P. Oxidative stress in diabetic macrovascular disease: does homocysteine play a role? South Med J. 1997. 90(9):903–906.
29. Racek J, Rusnkov H, Trefil L, Siala KK. The Influence of folate and antioxidants on homocysteine levels and oxidative stress in patients with hyperlipidemia and hyperhomocysteinemia. Physiol Res. 2005. 54(1):87–95.
30. Varillo AR, Ade T, Golia R, Nunziata V. The relationship between glycosylated haemoglobin levels and various degrees of glucose intolerance. Diabetologia. 1983. 24(5):391–393.
31. Andersson A, Brattström L, Israelsson B, Isaksson A, Hamfelt A, Hultberg B. Plasma homocysteine before and after methionine loading with regarding to age, gender, and menopausal status. Eur J Clin Invest. 1992. 22(2):74–87.
32. Brattstrom L. Vitamins as homocysteine-lowering agents. J Nutr. 1996. 126(4):1276s–1280s.
33. Jacques PF, Selhub J, Bostom AG, Wilson PW, Rosenberg IH. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med. 1999. 340(19):1449–1454.
34. Targher G, Bertolini L, Zenari L, Cacciatori V, Muggeo M, Faccini G, Zppini G. Cigarette smoking and plasma total homocysteine levels in young adults with type 1 diabetes. Diabetes Care. 2000. 23(4):524–528.
35. Chauvear P, Chadefaux B, Coud M, Aupetit J, Kamoun P, Jungers P. Long-term folic acid (but not pyridoxine) supplementation lowers elevated plasma homocysteine level in chronic renal failure. Miner Electrolyte Metab. 1996. 22(1-3):106–109.
36. Hoogeveen EK, Kostense PJ, Jakobs C, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Stehouwer CD. Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes 5-year follow-up of the Hoorn Study. Circulation. 2000. 101(13):1506–1511.
37. Jager A, Kostense PJ, Nijpels G, Dekker JM, Heine RJ, Bouter LM, Donker AJ, Stehouwer CD. Serum Homocysteine levels are associated with the development of microalbuminuria: the Hoorn Study. Arterioscler Thromb Vasc Biol. 2001. 21(1):74–81.
38. Araki A, Sako Y, Ito H. Plasma homocysteine concentrations in Japanese patients with non-insulin-dependent diabetes mellitus: effect of parenteral methylcobalamin treatment. Atherosclerosis. 1993. 103(2):149–157.
39. Buysschaert M, Dramais AS, Wallemacq PE, Hermans MP. Hyperhomocysteinemia in type 2 diabetes: relationship to macroangiopathy, nephropathy, and insulin resistance. Diabetes Care. 2000. 23(12):1816–1822.
40. Hoogeveen EK, Kostense PJ, Beks PJ, Mackaay AJ, Jakobs C, Bouter LM, Heine RJ, Stehouwer CD. Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin-dependent diabetes mellitus: a population-based study. Arterioscler Thromb Vasc Biol. 1998. 18(1):133–138.
41. Nygård O, Vollset SE, Refsum H, Stensvold I, Tverdal A, Nordrehaug JE, Ueland M, Kvåle G. Total plasma homocysteine and cardiovascular risk profile: the Hordaland Homocysteine Study. JAMA. 1995. 274(19):1526–1533.
42. Song IJ, Lee JA, Lim HS. Dietary and health-related lifestyle habits and blood parameters of non-insulin dependent diabetes patients. Nutr Sci. 2005. 8(1):35–41.
43. Nappo F, De Rosa N, Marfella F, De Lucia D, Ingrosso D, Perna AF, Fazati B, Giugliano D. Impairment of endothelial functions by acute hyperhomocysteinemia and reversal by antioxidant vitamins. JAMA. 1999. 281(22):2113–2118.
44. Young IS, Lightbody JH, McMaster D, Trimble ER. The effects of desferrioxamine and ascorbate on oxidative stress in the streptozotocin diabetic rat. Free Radic Biol Med. 1995. 18(5):833–840.
45. Kim NE, Kim WK. Effects of antioxidant vitamin supplementation on antioxidative status and plasma lipid profiles in Korean NIDDM patients. Korean J Nutr. 1999. 32(7):775–780.
46. Chambers JC, McGregor A, Jean-Marie J, Obeid OA, Kooner JS. Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia: an effect reversible with vitamin C therapy. Circulation. 1999. 99(9):1156–1160.
47. Shukla N, Angelini GD, Jeremy JY. The administration of folic acid reduces intravascular oxidative stress in diabetic rabbits. Metabolism. 2008. 57(6):774–781.
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