EFFECT OF ALPHA LIPOIC ACID IN TREATMENT OF TYPE 2 DIABETES
Â Objective: Antioxidant probably can prevent the progression and complications of Type 2 diabetes mellitus (T2DM). Due to effectiveness of alpha lipoic acid (ALA) as an antioxidant, this study was done in T2DM patients to evaluate the effect of ALA on their diabetic status, lipid profile, and oxidative stress (OS) status.
Methods: A total of 35 patients with diabetes were selected randomly who were under insulin treatment mainly and grouped as Group â€œA.â€ Another age- and sex-matched healthy controls selected grouped as â€œB.â€ Both groups supplemented with ALA (300 mg/day) for 6 months continuously. All parameters were tested before and after the supplementation.
Results: There was a significant decrease in fasting blood sugar from 161 to 122 mg/dl in Group â€œAâ€ and from 98 to 90 mg/dl in Group â€œB.â€ Postprandial blood sugar (PPBS) and glycosylated hemoglobin (HbA1c) levels also significantly decreased from 211 to 158 mg/dl and 8.81% to 7.2%, respectively, in Group â€œA.â€ PPBS levels significantly decreased from 130 to 124 mg/dl in Group â€œB,â€ but HbA1c% decreased insignificantly from 5.26% to 5.24% in Group â€œB.â€ Lipid profile parameters decreased in both groups except triglyceride level, which show insignificant relation in Group â€œB.â€ OS marker malondialdehyde significantly decreased from 1.967 to 1.592 nm/ml in Group â€œAâ€ and from 0.613 to 0.472 nm/ml in Group â€œB.â€ Plasma antioxidant glutathione shows a significant increase in both groups from 2.117 to 2.405 Î¼mol/L in Group â€œAâ€ and from 2.631 to 2.811 Î¼mol/L in Group â€œB.â€ Plasma nitric oxide also shows significant increase in both groups from 1.712 to 1.990 Î¼mol/L and from 2.139 to 2.318 Î¼mol/L, respectively.
Conclusion: Therefore, ALA is a potent antioxidant and can be used against oxidative injury associate with T2DM.
2. Jayesh BD, Snehal NM, Archana RJ. Diabetic nephropathy - Genesis, prevention and treatment. Int J Pharm Pharm Sci 2014;6(9):42-7.
3. International Diabetes Federation. Diabetes Atlas. Belgium: International Diabetes Federation; 2011. p. 14.
4. Kuchake VG, Upasani CD. Effect of vitamin E and C plus reduced glutathione in treatment of diabetic nephropathy. Int J Pharm Pharm Res 2013;2(12):1-5.
5. Stancoven A, McGuire DK. Preventing macrovascular complications in Type 2 diabetes mellitus: Glucose control and beyond. Am J Cardiol 2007;99(IIA):5-11.
6. Kaliamurthi S, Selvaraj G. Insight on solid lipid nanoparticles: Characterization and application in diabetes mellitus. J Crit Rev 2016;3(4):11-6.
7. Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Are oxidative stressâ€“activated signaling pathways mediators of insulin resistance and ÃŸ-cell dysfunction? Diabetes 2003;52(1):1-8.
8. Paolisso G, Dâ€™Amore A, Galzerano D, Balbi V, Giugliano D, Varricchio M, et al. Daily vitamin E supplements improve metabolic control but not insulin secretion in elderly Type II diabetic patients. Diabetes Care 1993;16(11):1433-7.
9. Jacob S, Ruus P, Hermann R, Tritschler HJ, Maerker E, Renn W, et al. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with Type 2 diabetes mellitus: A placebo-controlled pilot trial. Free Radic Biol Med 1999;27(3-4):309-14.
10. Akilandeswari V, Sekkizhar M, Santhakumari AS, Nirmala P. Nephroprotective effect of lycopene in hyperglycemia induced oxidative stress in male wistar rats. Int J Curr Pharm Res 2015;7(2):77-9.
11. Skrha J, Sindelka G, Kvasnicka J, Hilgertova J. Insulin action and fibrinolysis influenced by vitamin E in obese Type 2 diabetes mellitus. Diabetes Res Clin Pract 1999;44(4):27-33.
12. Packer L, Witt EH, Tritschler HJ. Alpha-lipoic acid as a biological antioxidant. Free Radic Biol Med 1995;19(2):227-50.
13. Blumenthal SA. Inhibition of gluconeogenesis in rat liver by lipoic acid. Evidence for more than one site of action. Biochem J 1984;219(3):773-80.
14. Amom Z, Zakaria Z, Mohamed J, Azlan A, Bahari H, Taufik HB, et al. Lipid lowering effect of antioxidant alpha-lipoic acid in experimental atherosclerosis. J Clin Biochem Nutr 2008;43(2):88-94.
15. Zulkhairi A, Zaiton Z, Jamaluddin M, Sharida F, Mohd TH, Hasnah B, et al. Alpha lipoic acid possess dual antioxidant and lipid lowering properties in atherosclerotic-induced New Zealand white rabbit. Biomed Pharmacother 2008;62(10):716-22.
16. Del Prato S, Marchetti P. Beta- and alpha-cell dysfunction in Type 2 diabetes. Horm Metab Res 2004;36(11-12):775-81.
17. Duckworth WC. Hyperglycemia and cardiovascular disease. Curr Atheroscler Rep 2001;3(5):383-91.
18. Mathis D, Vence L, Benoist C. Beta-cell death during progression to diabetes. Nature 2001;414(6865):792-8.
19. Kant R, Ramesh B, Garima K, Rubina B. Development and validation of novel spectrophotometric methods for simultaneous estimation of pioglitazone and metformin in bulk and fixed dasage forms by area under curve and dual wavelength mode. Int J Appl Pharm 2016;8(3):48-53.
20. Evans JL, Goldfine ID. Î‘-lipoic acid: A multifunctional antioxidant that improves insulin sensitivity in patients with Type 2 diabetes. Diabetes Technol Ther 2000;2(3):401-13.
21. Jacob S, Henriksen EJ, Schiemann AL, Simon I, Clancy DE, Tritschler HJ, et al. Enhancement of glucose disposal in patients with Type 2 diabetes by alpha-lipoic acid. Arzneimittelforschung 1995;45(8):872-4.
22. Borcea V, Nourooz-Zadeh J, Wolff SP, Klevesath M, Urich M, Peter W, et al. Î±-lipoic acid decreases oxidative stress even in diabetic patients with poor glycemic control and albuminuria. Free Radic Biol Med 1999;26(11-12):1495-500.
23. Khamaisi M, Rudich A, Potashnik R, Tritschler HJ, Gutman A, Bashan N. Lipoic acid acutely induces hypoglycemia in fasting non-diabetic and diabetic rats. Metabolism 1999;48(4):504-10.
24. Estrada DE, Ewart HS, Tsakiridis T, Volchuk A, Ramlal T, Tritschler H, et al. Stimulation of glucose uptake by the natural coenzyme Î±-lipoic acid/thioctic acid: Participation of elements of the insulin signaling pathway. Diabetes 1996;45(12):1798-804.
25. Mazzone T, Foster D, Chait A. In vivo stimulation of low density lipoprotein degradation by insulin. Diabetes 1984;33(4):333-8.
26. Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001;17(10):888-95.
27. Maritim AC, Sanders RA, Watkins JB 3rd. Effect of Î±-lipoic acid on biomarkers of oxidative stress in streptozotocin-induced diabetic rats. J Nutr Biochem 2003;14(5):288-94.
28. Kandeil MA, Amin KA, Hassanin KA, Ali KM, Mohammed ET. Role of lipoic acid on insulin resistance and leptin in experimentally diabetic rats. J Diabetes Complications 2011;25(1):31-8.
29. Ansar H, Mazloom Z, Kazemi F, Hejezi N. Effect of alpha-lipoic acid on blood glucose, insulin resistance, and glutathione peroxidase of Type 2 diabetic patients. Saudi Med J 2011;32(6):584-8.
30. Konrad D. Utilization of the insulin-signaling network in the metabolic actions of alpha-lipoic acid-reduction or oxidation? Antioxid Redox Signal 2005;7(7-8):1032-9.
31. Sasvari M, Nyakas C. Time dependent changes in oxidative metabolism during chronic diabetes in rats. Acta Biol Szeged 2003;47(1-4):153-8.
32. Bitar MS, Wahid S, Pilcher CW, Al-Saleh E, Al-Mulla F. Alpha lipoic acid mitigates insulin resistance in Goto-Kakizaki rats. Horm Metab Res 2004;36(8):542-9.
33. Moini H, Packer L, Saris NE. Antioxidant and prooxidant activities of Î±-lipoic acid and dihydrolipoic acid. Toxicol Appl Pharmacol 2002;182(1):84-90.
34. Monnier L, Colette C, Percheron C, Descomps B. Insulin, diabetes and cholesterol metabolism. C R Seances Soc Biol Fil 1995;189(5):919-31.
35. Abdel-Azim SA, Bader AM, Barakat MA. Effect of metformin, glyburide, and/or selenium on glucose homeostasis, lipid peroxidation, glutathione levels and changes in glutathione peroxidase activity in streptozotocin-induced diabetic rats. Egypt J Biochem 2002;20:393-411.
36. Sheela CG, Augusti KT. Antidiabetic effects of S-ally cysteine sulphoxide isolated from garlic Allium sativum Linn. Indian J Exp Biol 1992;30(6):523-6.
37. Sobenin IA, Tertov VV, Orekhov AN. Characterization of chemical composition of native and modified low-density lipoprotein occurring in the blood of diabetic patients. Int Angiol 1994;13(1):78-83.
38. Venkateswaran S, Pari L, Saravanan G. Effect of Phaseolus vulgaris on circulatory antioxidants and lipids in rats with streptozoticin induced diabetes. J Med Food 2002;5(2):97-103.
39. Suryawanshi NP, Bhutey AK, Nagdeote AN, Jadhav AA, Manoorkar GS. Study of lipid peroxide and lipid profile in diabetes mellitus. Indian J Clin Biochem 2006;21(1):126-30.
40. Kocak G, Aktan F, Canbolat O, Ozogul C, Elbeg S, Yildizoglu-Ari N, et al. Alpha-lipoic acid treatment ameliorates metabolic parameters, blood pressure, vascular reactivity and morphology of vessels already damaged by streptozotocin-diabetes. Diabetes Nutr Metab 2000;13(6):308-18.
41. Song KH, Lee WJ, Koh JM, Kim HS, Youn JY., Park HS, et al. Alpha-lipoic acid prevents diabetes mellitus in diabetes-prone obese rats. Biochem Biophys Res Commun 2005;326(1):197-202.
42. Lee WJ, Song KH, Koh EH, Won JC, Kim HS, Park HS, et al. Î±-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle. Biochem Biophys Res Commun 2005;332(3):885-91.
43. Woodhouse PR, Khaw K. Seasonal variations in vitamin C status, infection, fibrinogen and cardiovascular disease - Are they linked? Age Ageing 1994;23(2):5.
44. Aronson D. Cross-linking of glycated collagen in the pathogenesis of arterial and myocardial stiffening of aging and diabetes. J Hypertens 2003;21(1):3-12.
45. Lu SC. Regulation of hepatic glutathione synthesis: Current concepts and controversies. FASEB J 1999;13(10):1169-83.
46. Feng B, Yan XF, Xue JL, Xu L, Wang H. The protective effects of Î±-lipoic acid on kidneys in Type 2 diabetic Goto-Kakisaki rats via reducing oxidative stress. Int J Mol Sci 2013;14(4):6746-56.
47. Ceriello A. Oxidative stress and glycemic regulation. Metabolism 2000;492 Suppl 1:27-9.
48. Giugliano D, Ceriello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care 1996;19(3):257-67.
49. Hughes K, Choo M, Kuperan P, Ong CN, Aw TC. Cardiovascular risk factors in non-insulin dependent diabetics compared to non-diabetic controls: A population based survey among Asians in Singapore. Atheroscler J 1998;136(1):25-31.
50. Jain SK, McVie R. Effect of glycemic control, race (white versus black) and duration of diabetes on reduced glutathione content in erythrocytes of diabetic patients. Metabolism 1994;43(3):306-9.
51. Oberley LW. Free radicals and diabetes. J Free Radic Biol Med 1988;5(2):113-24.
52. Horie S, Ishii H, Suga T. Changes in peroxisomal fatty acid oxidation in diabetic rat liver. J Biochem 1981;90(6):1691-6.
53. Acworth IN, Mccabe DR, Maher TJ. The analysis of free radicals, their reaction products, and antioxidants. In Baskin SI, Salem H, editors. Oxidants, Antioxidants and Free Radicals. Ch. 2. Washington, DC: Taylor and Francis; 1997.
54. Singh U, Jialal I. Alpha-lipoic acid supplementation and diabetes. Nutr Rev 2008;66(11):646-57.
55. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2005;28 Suppl 1:S37-43.
56. Aragno M, Tamango E, Gatto V, Brignardello E, Parola S, Danni O, et al. Dehydroepiandrosterone protects tissues of streptozoticin-treated rats against oxidative stress. Free Radic Biol Med 1999;26(11-12):1467-74.
57. Malarkodi KP, Sivaprasad R, Varalakshmi P. Effect of lipoic acid on the oxidoreductive status of red blood cells in rats subject to oxidative stress by chronic administration of adriamycin. Hum Exp Toxicol 2004;23(3):129-35.
58. ArambaÅ¡iÄ‡ J, MihailoviÄ‡ M, UskokoviÄ‡ A, DiniÄ‡ S, GrdoviÄ‡ N, MarkoviÄ‡ J, et al. Alpha-lipoic acid upregulates antioxidant enzyme gene expression and enzymatic activity in diabetic rat kidneys through an O-GlcNAc-dependent mechanism. Eur J Nutr 2013;52(5):1461-73.
59. Becker BF. Towards the physiological function of uric acid. Free Radic Biol Med 1993;14(6):615-31.
60. Mcllduff CE, Rutkove SB. Critical appraisal of the use of alpha lipoic acid (thioctic acid) in the treatment of symptomatic diabetic polyneuropathy. Ther Clin Risk Manag 2011;7:377-85.
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