Effects of zinc supplementation on diabetes mellitus: a systematic review and meta-analysis

R Jayawardena, P Ranasinghe, P Galappatthy, Rldk Malkanthi, Gr Constantine, P Katulanda, R Jayawardena, P Ranasinghe, P Galappatthy, Rldk Malkanthi, Gr Constantine, P Katulanda

Abstract

The number of people with diabetes and pre-diabetes are exponentially increasing. Studies on humans have shown the beneficial effects of Zinc supplementation in patients with diabetes. The present study aims to systematically evaluate the literature and meta-analyze the effects of Zinc supplementation on diabetes. A systematic review of published studies reporting the effects of Zinc supplementations on diabetes mellitus was undertaken. The literature search was conducted in the following databases; PubMed, Web of Science and SciVerse Scopus. A meta-analysis of studies examining the effects of Zinc supplementation on clinical and biochemical parameters in patients with diabetes was performed. The total number of articles included in the present review is 25, which included 3 studies on type-1 diabetes and 22 studies on type-2 diabetes. There were 12 studies comparing the effects of Zinc supplementation on fasting blood glucose in patients with type-2 diabetes. The pooled mean difference in fasting blood glucose between Zinc supplemented and placebo groups was 18.13mg/dl (95%CI:33.85,2.41; p<0.05). 2-h post-prandial blood sugar also shows a similar distinct reduction in (34.87mg/dl [95%CI:75.44; 5.69]) the Zinc treated group. The reduction in HbA1c was 0.54% (95%CI:0.86;0.21) in the Zinc treated group. There were 8 studies comparing the effects of Zinc supplementation on lipid parameters in patients with type-2 diabetes. The pooled mean difference for total cholesterol between Zinc supplemented and placebo groups was 32.37mg/dl (95%CI:57.39,7.35; p<0.05). Low-density lipoprotein cholesterol also showed a similar distinct reduction in the Zinc treated group, the pooled mean difference from random effects analysis was 11.19mg/dl (95%CI:21.14,1.25; p<0.05). Studies have also shown a significant reduction in systolic and diastolic blood pressures after Zinc supplementation. This first comprehensive systematic review and meta-analysis on the effects of Zinc supplementation in patients with diabetes demonstrates that Zinc supplementation has beneficial effects on glycaemic control and promotes healthy lipid parameters. Further studies are required to identify the exact biological mechanisms responsible for these results.

Figures

Figure 1
Figure 1
Summarized search strategy.
Figure 2
Figure 2
Forest plots showing effects of Zinc Supplementation on; a) Fasting Blood Glucose (FBG), b) 2-h Post Prandial Blood Glucose (2-h PPBS), c) Glycated Haemoglobin (HbA1C) (IV-Inverse variance).
Figure 3
Figure 3
Forest plots showing effects of Zinc Supplementation on; a) Total Cholesterol (TC), b) LDL Cholesterol, c) HDL Cholesterol, d) Triglycerides (TG) (IV-Inverse variance).

References

    1. Wild S, Roglic G, Green A, Sicree R, King H. Global Prevalence of Diabetes. Diabetes Care. 2004. pp. 1047–1053.
    1. WHO. Diabetes Fact Sheet. .
    1. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27:1047–1053. doi: 10.2337/diacare.27.5.1047.
    1. IDF. Diabetes Atlas - The Economic Impacts of Diabetes. .
    1. Levin M, Pfeifer M. Uncomplicated Guide To Diabetes Complications. 3. American Diabetes Association, Alexandria, Virginia; 2009.
    1. Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005;365:1333–1346. doi: 10.1016/S0140-6736(05)61032-X.
    1. Dodson G, Steiner D. The role of assembly in insulins biosynthesis. Curr Opin Struct Biol. 1998;8:189–194. doi: 10.1016/S0959-440X(98)80037-7.
    1. Noormagi A, Gavrilova J, Smirnova J, Tougu V, Palumaa P. Zn(II) ions co-secreted with insulin suppress inherent amyloidogenic properties of monomeric insulin. Biochem J. 2010;430:511–518. doi: 10.1042/BJ20100627.
    1. Zalewski P, Millard S, Forbes I, Kapaniris O, Slavotinek S, Betts W, Ward A, Lincoln S, Mahadevan I. Video image analysis of labile Zn in viable pancreatic islet cells using specific fluorescent probe for Zn. J Histochem Cytochem. 1994;42:877–884. doi: 10.1177/42.7.8014471.
    1. Arquilla ER, Packer S, Tarmas W, Miyamoto S. The effect of zinc on insulin metabolism. Endocrinology. 1978;103:1440–1449. doi: 10.1210/endo-103-4-1440.
    1. Chausmer AB. Zinc, insulin and diabetes. J Am Coll Nutr. 1998;17:109–115.
    1. Kelly F. Use of antioxidants in the prevention and treatment of disease. J Int Fed Clin Chem. 1998;10:21–23.
    1. Garg VK, Gupta R, Goyal RK. Hypozincemia in diabetes mellitus. J Assoc Physicians India. 1994;42:720–721.
    1. Pidduck HG, Wren PJ, Evans DA. Hyperzincuria of diabetes mellitus and possible genetical implications of this observation. Diabetes. 1970;19:240–247.
    1. Black RE. Zinc deficiency, infectious disease and mortality in the developing world. J Nutr. 2003;133:1485S–1489S.
    1. Simon SF, Taylor CG. Dietary zinc supplementation attenuates hyperglycemia in db/db mice. Exp Biol Med (Maywood) 2001;226:43–51.
    1. Faure P, Benhamou PY, Perard A, Halimi S, Roussel AM. Lipid peroxidation in insulin-dependent diabetic patients with early retina degenerative lesions: Effects of an oral zinc supplementation. Eur J Clin Nutr. 1995;49:282–288.
    1. Shidfar F, Aghasi M, Vafa M, Heydari I, Hosseini S, Shidfar S. Effects of combination of zinc and vitamin A supplementation on serum fasting blood sugar, insulin, apoprotein B and apoprotein A-I in patients with type i diabetes. International Journal of Food Sciences and Nutrition. 2010;61:182–191. doi: 10.3109/09637480903334171.
    1. Afkhami-Ardekani M, Karimi M, Mohammadi SM, Nourani F. Effect of zinc sulfate supplementation on lipid and glucose in type 2 diabetic patients. Pak J Nutr. 2008;7:550–553. doi: 10.3923/pjn.2008.550.553.
    1. Al-Maroof RA, Al-Sharbatti SS. Serum zinc levels in diabetic patients and effect of zinc supplementation on glycemic control of type 2 diabetics. Saudi Medical Journal. 2006;27:344–350.
    1. Ioannidis JP. Contradicted and initially stronger effects in highly cited clinical research. JAMA. 2005;294:218–228. doi: 10.1001/jama.294.2.218.
    1. de Sena KC, Arrais RF. das Gracas Almeida M, de Araujo DM, dos Santos MM, de Lima VT, de Fatima Campos Pedrosa L: Effects of zinc supplementation in patients with type 1 diabetes. Biol Trace Elem Res. 2005;105:1–9. doi: 10.1385/BTER:105:1-3:001.
    1. Freeman SR, Williams HC, Dellavalle RP. The increasing importance of systematic reviews in clinical dermatology research and publication. J Invest Dermatol. 2006;126:2357–2360. doi: 10.1038/sj.jid.5700560.
    1. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535. doi: 10.1136/bmj.b2535.
    1. Cochran WG. The combination of estimates from different experiments. Biometrics. 1954;10:101–129. doi: 10.2307/3001666.
    1. Higgins IP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–1558. doi: 10.1002/sim.1186.
    1. Anderson RA, Roussel AM, Zouari N, Mahjoub S, Matheau JM, Kerkeni A. Potential antioxidant effects of zinc and chromium supplementation in people with type 2 diabetes mellitus. J Am Coll Nutr. 2001;20:212–218.
    1. Farvid MS, Homayouni F, Amiri Z, Adelmanesh F. Improving neuropathy scores in type 2 diabetic patients using micronutrients supplementation. Diabetes Research and Clinical Practice. 2011;93:86–94. doi: 10.1016/j.diabres.2011.03.016.
    1. Farvid MS, Jalali M, Siassi F, Hosseini M. Comparison of the effects of vitamins and/or mineral supplementation on glomerular and tubular dysfunction in type 2 diabetes. Diabetes Care. 2005;28:2458–2464. doi: 10.2337/diacare.28.10.2458.
    1. Farvid MS, 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.
    1. Farvid MS, Siassi F, Jalali M, Hosseini M, Saadat N. The impact of vitamin and/or mineral supplementation on lipid profiles in type 2 diabetes. Diabetes Research and Clinical Practice. 2004;65:21–28. doi: 10.1016/j.diabres.2003.11.009.
    1. Garcia-Medina JJ, Pinazo-Duran MD, Garcia-Medina M, Zanon-Moreno V, Pons-Vazquez S. A 5-year follow-up of antioxidant supplementation in type 2 diabetic retinopathy. Eur J Ophthalmol. 2011;21:637–643. doi: 10.5301/EJO.2010.6212.
    1. Gunasekara P, Hettiarachchi M, Liyanage C, Lekamwasam S. Effects of zinc and multimineral vitamin supplementation on glycemic and lipid control in adult diabetes. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2011;4:53–60.
    1. Hussain SA, Khadim HM, Khalaf BH, Ismail SH, Hussein KI, Sahib AS. Effects of melatonin and zinc on glycemic control in type 2 diabetic patients poorly controlled with metformin. Saudi Med J. 2006;27:1483–1488.
    1. Kadhim HM, Ismail SH, Hussein KI, Bakir IH, Sahib AS, Khalaf BH, Hussain SA. Effects of melatonin and zinc on lipid profile and renal function in type 2 diabetic patients poorly controlled with metformin. J Pineal Res. 2006;41:189–193. doi: 10.1111/j.1600-079X.2006.00353.x.
    1. Parham M, Amini M, Aminorroaya A, Heidarian E. Effect of zinc supplementation on microalbuminuria in patients with type 2 diabetes: A double blind, randomized, placebo-controlled, cross-over trial. Review of Diabetic Studies. 2008;5:102–109. doi: 10.1900/RDS.2008.5.102.
    1. Partida-Hernndez G, Arreola F, Fenton B, Cabeza M, Romn-Ramos R, Revilla-Monsalve MC. Effect of zinc replacement on lipids and lipoproteins in type 2-diabetic patients. Biomed Pharmacother. 2006;60:161–168. doi: 10.1016/j.biopha.2006.02.004.
    1. Blostein-Fujii A, DiSilvestro RA, Frid D, Katz C, Malarkey W. Short-term zinc supplementation in women with non-insulin-dependent diabetes mellitus: Effects on plasma 5'-nucleotidase activities, insulin- like growth factor I concentrations, and lipoprotein oxidation rates in vitro. Am J Clin Nutr. 1997;66:639–642.
    1. De Sena KCM, Arrais RF, Almeida MDG, De Arajo DM, Dos Santos MM, De Lima VT, Pedrosa LDFC. Effects of zinc supplementation in patients with type 1 diabetes. Biological Trace Element Research. 2005;105:1–9. doi: 10.1385/BTER:105:1-3:001.
    1. Gupta R, Garg VK, Mathur DK, Goyal RK. Oral zinc therapy in diabetic neuropathy. J Assoc Physicians India. 1998;46:939–942.
    1. Hayee MA, Mohammad QD, Haque A. Diabetic neuropathy and zinc therapy. Bangladesh Med Res Counc Bull. 2005;31:62–67.
    1. Hegazi SM, Ahmed SS, Mekkawy AA, Mortagy MS, Abdelkadder M. Effect Of Zinc Supplementation on Serum Glucose, Insulin, Glucagon, Glucose-6-Phosphatase and Mineral levels in Diabetics. Journal of Clinical Biochemistry and Nutrition. 1992;12:209–215. doi: 10.3164/jcbn.12.209.
    1. Heidarian E, Amini M, Parham M, Aminorroaya A. Effect of zinc supplementation on serum homocysteine in type 2 diabetic patients with microalbuminuria. Review of Diabetic Studies. 2009;6:38–44.
    1. Niewoehner CB, Allen JI, Boosalis M. Role of zinc supplementation in type II diabetes mellitus. Am J Med. 1986;81:63–68.
    1. Raz I, Karsai D, Katz M. The influence of zinc supplementation on glucose homeostasis in NIDDM. Diabetes Research. 1989;11:73–79.
    1. Roussel AM, Kerkeni A, Zouari N, Mahjoub S, Matheau JM, Anderson RA. Antioxidant effects of zinc supplementation in Tunisians with type 2 diabetes mellitus. J Am Coll Nutr. 2003;22:316–321.
    1. Seet RCS, Lee CYJ, Lim ECH, Quek AML, Huang H, Huang SH, Looi WF, Long LH, Halliwell B. Oral zinc supplementation does not improve oxidative stress or vascular function in patients with type 2 diabetes with normal zinc levels. Atherosclerosis. 2011;219:231–239. doi: 10.1016/j.atherosclerosis.2011.07.097.
    1. Yoshikawa Y, Ueda E, Miyake H, Sakurai H, Kojima Y. Insulinomimetic bis(maltolato)zinc(II) complex: blood glucose normalizing effect in KK-A(y) mice with type 2 diabetes mellitus. Biochem Biophys Res Commun. 2001;281:1190–1193. doi: 10.1006/bbrc.2001.4456.
    1. Haase H, Maret W. Protein tyrosine phosphatases as targets of the combined insulinomimetic effects of zinc and oxidants. Biometals. 2005;18:333–338. doi: 10.1007/s10534-005-3707-9.
    1. Tang X, Shay NF. Zinc has an insulin-like effect on glucose transport mediated by phosphoinositol-3-kinase and Akt in 3T3-L1 fibroblasts and adipocytes. J Nutr. 2001;131:1414–1420.
    1. Wijesekara N, Chimienti F, Wheeler MB. Zinc, a regulator of islet function and glucose homeostasis. Diabetes Obes Metab. 2009;11(Suppl 4):202–214.
    1. Rutter GA. Think zinc: New roles for zinc in the control of insulin secretion. Islets. 2010;2:49–50. doi: 10.4161/isl.2.1.10259.
    1. Prospective UK. Diabetes Study (UKPDS) Group: Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:854–865.
    1. Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control over 30weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care. 2005;28:1083–1091. doi: 10.2337/diacare.28.5.1083.
    1. Foster M, Petocz P, Samman S. Effects of zinc on plasma lipoprotein cholesterol concentrations in humans: a meta-analysis of randomised controlled trials. Atherosclerosis. 2010;210:344–352. doi: 10.1016/j.atherosclerosis.2009.11.038.
    1. Hughes S, Samman S. The effect of zinc supplementation in humans on plasma lipids, antioxidant status and thrombogenesis. J Am Coll Nutr. 2006;25:285–291.
    1. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001;119:1417–1436.
    1. Leitzmann MF, Stampfer MJ, Wu K, Colditz GA, Willett WC, Giovannucci EL. Zinc supplement use and risk of prostate cancer. J Natl Cancer Inst. 2003;95:1004–1007. doi: 10.1093/jnci/95.13.1004.
    1. Chandra RK. Excessive intake of zinc impairs immune responses. JAMA. 1984;252:1443–1446. doi: 10.1001/jama.1984.03350110043027.
    1. Boukaiba N, Flament C, Acher S, Chappuis P, Piau A, Fusselier M, Dardenne M, Lemonnier D. A physiological amount of zinc supplementation: effects on nutritional, lipid, and thymic status in an elderly population. Am J Clin Nutr. 1993;57:566–572.
    1. Mahboob M, Rahman MF, Grover P. Serum lipid peroxidation and antioxidant enzyme levels in male and female diabetic patients. Singapore Med J. 2005;46:322–324.
    1. Powell SR. The antioxidant properties of zinc. J Nutr. 2000;130:1447S–1454S.
    1. Prasad AS, Bao B, Beck FW, Kucuk O, Sarkar FH. Antioxidant effect of zinc in humans. Free Radic Biol Med. 2004;37:1182–1190. doi: 10.1016/j.freeradbiomed.2004.07.007.
    1. Payne-Robinson HM, Golden MH, Golden BE, Simeon DT. The zinc sandwich and growth. Lancet. 1991;337:925–926.
    1. Beletate V, El Dib RP, Atallah AN. Zinc supplementation for the prevention of type 2 diabetes mellitus. Cochrane Database Syst Rev. 2007;30:CD005525.

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