Document Type : Original Article
Authors
Department of Endocrinology, Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
Abstract
Objective: Type 2 diabetes mellitus (DM‑T2) is commonly associated with increased
triglycerides (TG), low‑density lipoprotein cholesterol (LDL‑C) and low high‑density
lipoprotein cholesterol (HDL‑C) levels. Fibrates like gemfibrozil are frequently used in
diabetic patients to decrease TG and increase HDL‑C levels. We compared the efficacy of
Vitamin C, an antioxidant vitamin, with gemfibrozil on serum HDL‑C in diabetic patients.
Methods: Type 2 diabetic patients, referred to our out‑patient clinic were randomly divided
into three groups. After 1 month of lifestyle and diet modifications, groupsA, B, and C were
prescribed 1000 mg Vitamin C, 600 mg gemfibrozil and combination of both, respectively.
Before the study initiation and after 6th week of drug prescription, the blood samples were
taken and analyzed for total cholesterol (Total‑C), HDL‑C, TG, fasting blood sugar (FBS),
and hemoglobin A1c (HbA1c) levels.
Findings: Sixty‑seven patients entered, and 50 patients (18 male, 32 female) finished
the study. Overall, serum HDL‑C increased significantly from 39.8 to 45.2 mg/dL in the
participants (P = 0.001). HDL‑C increased 6.3, 4.4 and 5.0 mg/dL in groups A, B and C,
respectively (related significances were 0.017, 0.022 and 0.033, respectively). Significant
decrease of serum TG and Total‑C occurred in gemfibrozil and combination groups,
but not in Vitamin C group. Changes in serum HDL‑C between three groups were
not significant (P = 0.963). We found a significant decrease in TG and Total‑C in the
groups B and C (P < 0.05), but no significant changes of TG, Total‑C, LDL‑C, FBS and HbA1c
in group A (P > 0.05).
Conclusion: The results demonstrated that Vitamin C may have beneficial effects on HDL‑C
in diabetic patients without significant effects on plasma glucose or other lipid parameters;
however, its role for the treatment of low HDL‑C patients should be evaluated in larger
studies.
Keywords
- BetteridgeDJ. Diabetic dyslipidemia. Am J Med 1994;96:25S‑31.
2. Howard BV, Howard W J . D y s l i p i d e m i a i n
non‑insulin‑dependent diabetes mellitus. Endocr Rev
1994;15:263‑74.
3. Howard BV. Lipoprotein metabolism in diabetes. Curr Opin
Lipidol 1994;5:216‑20.
4. Tomkin GH, Owens D. Insulin and lipoprotein metabolism
with special reference to the diabetic state. Diabetes Metab
Rev 1994;10:225‑52.
5. Laakso M. Dyslipidemia, morbidity, and mortality in
non‑insulin‑dependent diabetes mellitus. Lipoproteins and
coronary heart disease in non‑insulin‑dependent diabetes
mellitus. J Diabetes Complications 1997;11:137‑41.
6. Laakso M. Lipid disorders in type 2 diabetes. Endocrinol Nutr
2009;56 Suppl 4:43‑5.
7. Caballero AE, Arora S, Saouaf R, Lim SC, Smakowski P,
Park JY, et al. Microvascular and macrovascular reactivity
is reduced in subjects at risk for type 2 diabetes. Diabetes
1999;48:1856‑62.
8. Sowers JR, Lester MA. Diabetes and cardiovascular disease.
Diabetes Care 1999;22 Suppl 3:C14‑20.
9. Franceschini G. Epidemiologic evidence for high‑density
lipoprotein cholesterol as a risk factor for coronary artery
disease. Am J Cardiol 2001;88 (12A):9N‑13.
10. Maron DJ. The epidemiology of low levels of high‑density
lipoprotein cholesterol in patients with and without coronary
artery disease. Am J Cardiol 2000;86:11L‑14.
11. Nofer JR, Kehrel B, Fobker M, Levkau B, Assmann G, von
Eckardstein A. HDL and arteriosclerosis: Beyond reverse
cholesterol transport. Atherosclerosis 2002;161:1‑16.
12. CallaMS, Lynch SM. Vitamin C preserves the cardio‑protective
paraoxonase activity of high‑density lipoprotein during
oxidant stress. Arch Biochem Biophys 2006;452:129‑37.
13. Kita T, Ishii K, Yokode M, Kume N, Nagano Y, Arai H,
et al. The role of oxidized low density lipoprotein in the
pathogenesis of atherosclerosis. Eur Heart J 1990;11 Suppl
E: 122‑7.
14. GargA, Grundy SM. Management of dyslipidemia in NIDDM.
Diabetes Care 1990;13:153‑69.
15. Garg A, Grundy SM. Gemfibrozil alone and in combination
with lovastatin for treatment of hypertriglyceridemia in
NIDDM. Diabetes 1989;38:364‑72.
16. Tong N, Liang J. The effect of gemfibrozil on serum apo C II
and C III in diabetic hyperlipidemia. Hua Xi Yi Ke Da Xue
Xue Bao 1991;22:409‑11.
17. Goldberg R, La Belle P, Zupkis R, Ronca P. Comparison of
the effects of lovastatin and gemfibrozil on lipids and glucose
control in non‑insulin‑dependent diabetes mellitus. Am J
Cardiol 1990;66:16B‑21.
18. Davidson MH, Armani A, McKenney JM, Jacobson TA.
Safety considerations with fibrate therapy. Am J Cardiol
2007;99:3C‑18.
19. Baer AN, Wortmann RL. Myotoxicity associated with
lipid‑lowering drugs. Curr Opin Rheumatol 2007;19:67‑73.
20. Vanholder R, Sever MS, Erek E, Lameire N. Rhabdomyolysis.
J Am Soc Nephrol 2000;11:1553‑61.
21. Chi X, May JM. Oxidized lipoprotein induces the macrophage
ascorbate transporter (SVCT2): Protection by intracellular
ascorbate against oxidant stress and apoptosis. Arch Biochem
Biophys 2009;485:174‑82.
22. Pinchuk I, Shoval H, Dotan Y, Lichtenberg D. Evaluation of
antioxidants: Scope, limitations and relevance of assays. Chem
Phys Lipids 2012;165:638‑47.
23. Niki E, Yamamoto Y, Komuro E, Sato K. Membrane damage
due to lipid oxidation. Am J Clin Nutr 1991;53:201S‑05.
24. Shibuya N, Humphers JM, Agarwal MR, Jupiter DC. Efficacy
and safety of high‑dose vitamin C on complex regional pain
syndrome in extremity trauma and surgery – Systematic
review and meta‑analysis. J Foot Ankle Surg 2013;52:62‑6.
25. Aro A, Kyllästinen M, Kostiainen E, Gref CG, Elfving S,
Uusitalo U. No effect on serum lipids by moderate and high
doses of vitamin C in elderly subjects with low plasma ascorbic
acid levels. Ann Nutr Metab 1988;32:133‑7.
26. Bazzarre TL, Kleiner SM, Ainsworth BE. Vitamin C intake and
lipid profiles of competitive male and female bodybuilders.
Int J Sport Nutr 1992;2:260‑71.
27. Hillstrom RJ, Yacapin‑Ammons AK, Lynch SM.
Vitamin C inhibits lipid oxidation in human HDL. J Nutr
2003;133:3047‑51. - 28. Bates CJ, Mandal AR, Cole TJ. H.D.L. cholesterol and
vitamin‑C status. Lancet 1977;2:611.
29. Bates CJ, Burr MK, St Leger AS. Vitamin C, high density
lipoproteins and heart disease in elderly subjects. Age Ageing
1979;8:177‑82.
30. Rezaian GR, Taheri M, Mozaffari BE, Mosleh AA,
Ghalambor MA. The salutary effects of antioxidant vitamins
on the plasma lipids of healthy middle aged‑to‑elderly
individuals: A randomized, double‑blind, placebo‑controlled
study. J Med Liban 2002;50:10‑3.
31. Yanai H, Morimoto M. Effect of ascorbate on serum lipids and
urate metabolism during exhaustive training. Clin Sci (Lond)
2004;106:107‑9.
32. Taskinen MR. Diabetic dyslipidemia. Atheroscler
Suppl 2002;3:47‑51.
33. Taskinen MR. Pathogenesis of dyslipidemia in type 2 diabetes.
Exp Clin Endocrinol Diabetes 2001;109 Suppl 2:S180‑8.
34. Anantharamaiah GM, Hughes TA, Iqbal M, Gawish A,
Neame PJ, Medley MF, et al. Effect of oxidation on the
properties of apolipoproteins A‑I and A‑II. J Lipid Res
1988;29:309‑18.
35. Nagano Y, Arai H, Kita T. High density lipoprotein loses
its effect to stimulate efflux of cholesterol from foam cells
after oxidative modification. Proc Natl Acad Sci U S A
1991;88:6457‑61.
36. Jacques PF, Sulsky SI, Perrone GE, JennerJ, Schaefer EJ. Effect
of vitamin C supplementation on lipoprotein cholesterol,
apolipoprotein, and triglyceride concentrations. Ann
Epidemiol 1995;5:52‑9.
37. Eteng MU, Ibekwe HA, Amatey TE, Bassey BJ, Uboh FU,
Owu DU. Effect of vitamin C on serum lipids and
electrolyte profile of albino Wistar rats. Niger J Physiol Sci
2006;21:15‑9.
38. Owu DU, Antai AB, Udofia KH, Obembe AO, Obasi KO,
Eteng MU. Vitamin C improves basal metabolic rate and lipid
profile in alloxan‑induced diabetes mellitus in rats. J Biosci
2006;31:575‑9.
39. Kim MK, Sasaki S, Sasazuki S, Okubo S, Hayashi M, Tsugane S.
Long‑term vitamin C supplementation has no markedly
favourable effect on serum lipids in middle‑aged Japanese
subjects. Br J Nutr 2004;91:81‑90.
40. McRae MP. Vitamin C supplementation lowers serum
low‑density lipoprotein cholesterol and triglycerides:
A meta‑analysis of 13 randomized controlled trials. J Chiropr
Med 2008;7:48‑58.
41. Ness AR, Khaw KT, Bingham S, Day NE. Vitamin C status
and serum lipids. Eur J Clin Nutr 1996;50:724‑9.
42. Slattery ML, Jacobs DR Jr, DyerA, Benson J, HilnerJE, Caan BJ.
Dietary antioxidants and plasma lipids: The CARDIA Study.
J Am Coll Nutr 1995;14:635‑42.
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