Turkiye Klinikleri Journal of Internal Medicine

.: REVIEW
Mineraller ve Diabetes Mellitus
Minerals and Diabetes Mellitus
Murat GÜRBÜZa, Menşure Nur ÇELİKb
aBeslenme ve Diyetetik Bölümü, Kırklareli Üniversitesi Sağlık Bilimleri Fakültesi, Kırklareli, TÜRKİYE
bBeslenme ve Diyetetik Bölümü, Gazi Üniversitesi Sağlık Bilimleri Fakültesi, Ankara, TÜRKİYE
Turkiye Klinikleri J Intern Med. 2019;4(2):71-83
doi: 10.5336/intermed.2018-64388
Article Language: TR
Full Text
ÖZET
 Mineraller, metabolizmada çeşitli fizyolojik reaksiyonlarda enzim kofaktörü olarak rol almasının yanında; elektrolit dengesinde, kemik dokunun korunması ve sürdürülmesinde, kan pıhtılaşmasında, sinir iletilerinin düzenlenmesinde önemli görevler üstlenmektedir. Çinko, krom, magnezyum, mangan, selenyum gibi birtakım minerallerin dolaşımdaki seviyeleri diyabet için önemli bir prediktör olabilmekte ve suplementasyonları diyabetik bireylerin sağlık durumlarında yararlı etkiler oluşturabilmektedir. Glukoz homeostazı pankreasın beta hücrelerinden salgılanan insülin hormonunun kontrolü ve koordinasyonu ile sağlanmaktadır. Vücuttaki insülinin üretilememesi veya kullanılamaması durumunda kan glukoz homeostazında bozulmalar meydana gelmekte ve vücuttan bazı minerallerin aşırı atılımı gerçekleşebilmektedir. Aşırı atılım ile gereksinimin artması sonucu glukoz metabolizma yolağında, beta hücre fonksiyonunda ve insülin sinyalizasyon kaskadında bozulmalar meydana gelebilmekte ve bu durum diyabet ve komplikasyonlarının patogenezine katkı sağlayabilmektedir. Bu çalışmada, bazı minerallerin vücuttaki seviyelerinin ve yapılan süplementasyonların diyabet ile ilişkisinin değerlendirilmesi amaçlanmıştır. Bu noktada, odaklandığımız mineraller; çinko, bakır, krom, magnezyum, mangan, bakır, demir, selenyum ve vanadyumdur. Yapılan çalışmalardan elde edilen sonuçlar, vücut mineral düzeyinin diyabet ile ilişkisinde bazı farklılıklar ortaya koymaktadır. Ayrıca, diyabetin önlenmesi veya yönetiminde mineral süplementasyonunun yeterli kanıtlar sağlayamadığını göstermektedir. Diyabet ve komplikasyonları açısından risk altında olan bireylerde dolaşımdaki mineral düzeyinin ve mineral süplementasyonun gerekliliğinin saptanması oldukça önemlidir ve bu noktada daha büyük örnekli ve daha uzun süreli takip gerektiren çalışmalarla desteklenen kanıtlara gereksinim duyulmaktadır.

Anahtar Kelimeler: Mineraller; diabetes mellitus; kan glukozu
ABSTRACT
 Minerals take an important role in electrolyte balance, preservation and maintenance of bone tissue, blood clotting, and regulation of nerve conduction as well as role as enzyme cofactor in various physiological reactions in metabolism. Circulating levels of a number of minerals, such as zinc, chromium, magnesium, manganese, selenium, may be an important predictor for diabetes, and their supplementation may have beneficial effects on the health status of diabetic individuals. Glucose homeostasis is provided by the control and coordination of insulin hormone secreted from beta cells of the pancreas. In the event that the insulin in the body cannot be produced or used, disruption of blood glucose homeostasis occurs and excessive excretion of some minerals from the body may occur. As a result of increased requirement with excessive excretion, in the glucose metabolism pathway, in beta-cell function and insulin signaling cascade may occur impairments and this occasion may contribute to the pathogenesis of diabetes and its complications. The aim of this review evaluate the relationship between levels and/or supplement of minerals and diabetes mellitus. At this point we focus on zinc, copper, chromium, magnesium, manganese, copper, iron, selenium and vanadium. The results obtained from the studies show some differences in the relationship of body mineral level and diabetes mellitus. It also shows that mineral supplementation in the prevention or management of diabetes cannot provide sufficient evidence. In individuals who are at risk for diabetes and its complications, it is important to determine the level of mineral in circulation and the need for mineral supplements. Therefore, there is need for evidence supported by studies that require larger sample size and longer follow-up.

Keywords: Minerals; diabetes mellitus; blood glucose
REFERENCES:
  1. Cavan D, Fernandes Jda R, Makaroff L, Ogurtsova K, Webber S. IDF Diabetes Atlas. 7th ed. Brussels, Belgium: International Diabetes Federation; 2015. p.136. [Link ]
  2. T.C. Sağlık Bakanlığı Türkiye Halk Sağlığı Kurumu. Türkiye Diyabet Programı 2015-2020. Ankara: T.C. Sağlık Bakanlığı; 2014. p.9.
  3. 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(5):1047-53. [Crossref] [PubMed]
  4. Türkiye Endokrinoloji ve Metabolizma Derneği Diabetes Mellitus Çalışma ve Eğitim Grubu. Diabetes Mellitus ve Komplikasyonlarının Tanı ve Tedavi İzlem Kılavuzu. 10. Baskı. Ankara: Bayt Matbaası; 2018. p.245.
  5. Bluestone JA, Herold K, Eisenbarth G. Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature. 2010;464(7293): 1293-300. [Crossref ] [PubMed] [PMC]
  6. Bhanot S, Thompson K, McNeill J. Essential trace elements of potential importance in nutritional management of diabetes mellitus. Nutrition Research. 1994;14(4):593-604. [Crossref]
  7. Ma J, Folsom AR, Melnick SL, Eckfeldt JH, Shar rett AR, Nabulsi AA, et al. Associations of serum and dietary magnesium with cardiovascular disease, hypertension, diabetes, insulin, and carotid arterial wall thickness: the ARIC study. J Clin Epidemiol. 1995;48(7):927-40. [Crossref]
  8. O?Connell BS. Select vitamins and minerals in the management of diabetes. Diabetes Spectrum. 2001;14(3):133-48. [Crossref ]
  9. Vincent AM, Russell JW, Low P, Feldman EL. Oxidative stress in the pathogenesis of diabetic neuropathy. Endocr Rev. 2004;25(4):612-28. [Crossref ] [PubMed]
  10. Meunier N, O'Connor J, Maiani G, Cashman K, Secker D, Ferry M, et al. Importance of zinc in the elderly: the ZENITH study. Eur J Clin Nutr. 2005;59 Suppl 2:S1-4. [Crossref] [PubMed]
  11. Song Y, Wang J, Li XK, Cai L. Zinc and the diabetic heart. Biometals. 2005;18(4):325-32. [Crossref] [PubMed]
  12. Kelleher SL, McCormick NH, Velasquez V, Lopez V. Zinc in specialized secretory tissues: roles in the pancreas, prostate, and mammary gland. Adv Nutr. 2011;2(2):101-11. [Crossref ] [PubMed] [PMC]
  13. Vardatsikos G, Pandey NR, Srivastava AK. Insulino-mimetic and anti-diabetic effects of zinc. J Inorg Biochem. 2013;120:8-17. [Crossref] [PubMed]
  14. Wijesekara N, Dai FF, Hardy AB, Giglou PR, Bhattacharjee A, Koshkin V, et al. Beta cellspecific Znt8 deletion in mice causes marked defects in insulin processing, crystallisation and secretion. Diabetologia. 2010;53(8):165668. [Crossref ] [PubMed] [PMC]
  15. Pidduck HG, Wren PJ, Evans DA. Hyperzincuria of diabetes mellitus and possible genetical implications of this observation. Diabetes. 1970;19(4):240-7. [Crossref ] [ PubMed]
  16. Sjögren A, Florén CH, Nilsson Å. Magnesium, potassium and zinc deficiency in subjects with type II diabetes mellitus. Acta Med Scand. 1988;224(5):461-6. [Crossref ] [ PubMed]
  17. Bēgin-Heick N, Dalpē-Scott M, Rowe J, Heick HM. Zinc supplementation attenuates insulin secretory activity in pancreatic islets of the ob/ob mouse. Diabetes. 1985;34(2):179-84. [Crossref] [PubMed]
  18. Lau AL, Failla ML. Urinary excretion of zinc, copper and iron in the streptozotocin-diabetic rat. J Nutr. 1984;114(1):224-33. [Crossref] [PubMed]
  19. Jansen J, Karges W, Rink L. Zinc and diabetes--clinical links and molecular mechanisms. J Nutr Biochem. 2009;20(6):399-417. [Crossref] [PubMed]
  20. Kazi TG, Afridi HI, Kazi N, Jamali MK, Arain MB, Jalbani N, et al. Copper, chromium, manganese, iron, nickel, and zinc levels in biological samples of diabetes mellitus patients. Biol Trace Elem Res. 2008;122(1):1-18. [Crossref] [PubMed]
  21. El-Yazigi A, Legayada E. Urinary selenium in healthy and diabetic Saudi Arabians. Biol Trace Elem Res. 1996;52(1):55-63. [Crossref] [PubMed]
  22. Nasli-Esfahani E, Faridbod F, Larijani B, Ganjali MR, Norouzi P. Trace element analysis of hair, nail, serum and urine of diabetes mellitus patients by inductively coupled plasma atomic emission spectroscopy. Journal of Diabetes & Metabolic Disorders. 2011;10:1.
  23. Tunçdemir M, Ertürküner SP, Özçelik D. Investigation of lipid peroxidation and antiapoptotic effects of zinc aganist liver damage in diabetic rats. Hum Exp Toxicol. 2017;36(8): 813-22. [Crossref ] [PubMed]
  24. Elsaed WM, Mohamed HA. Dietary zinc modifies diabetic-induced renal pathology in rats. Ren Fail. 2017;39(1):246-57. [Crossref] [PubMed] [PMC]
  25. 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 Med J. 2006;27(3):344-50.
  26. 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(4):316-21. [Crossref ] [ PubMed]
  27. Heidarian E, Amini M, Parham M, Aminorroaya A. Effect of zinc supplementation on serum homocysteine in type 2 diabetic patients with microalbuminuria. Rev Diabet Stud. 2009;6(1):64-70. [Crossref ] [PubMed] [PMC]
  28. Jayawardena R, Ranasinghe P, Galappatthy P, Malkanthi R, Constantine G, Katulanda P. Effects of zinc supplementation on diabetes mellitus: a systematic review and meta-analysis. Diabetol Metab Syndr. 2012;4(1):13. [Crossref] [PubMed] [PMC]
  29. 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(3):212-8. [Crossref] [PubMed]
  30. Seet RC, Lee CY, Lim EC, Quek AM, Huang H, Huang SH, et al. Oral zinc supplementation does not improve oxidative stress or vascular function in patients with type 2 diabetes with normal zinc levels. Atherosclerosis. 2011;219(1):231-9. [Crossref ] [ PubMed]
  31. Sales CH, Pedrosa Lde F. Magnesium and diabetes mellitus: their relation. Clin Nutr. 2006;25(4):554-62. [Crossref ] [PubMed]
  32. Barbagallo M, Dominguez LJ, Galioto A, Ferlisi A, Cani C, Malfa L, et al. Role of magnesium in insulin action, diabetes and cardiometabolic syndrome X. Mol Aspects Med. 2003;24(1-3):39-52. [Crossref ]
  33. Suárez A, Pulido N, Casla A, Casanova B, Arrieta F, Rovira A. Impaired tyrosine-kinase activity of muscle insulin receptors from hypomagnesaemic rats. Diabetologia. 1995;38(11):1262-70. [Crossref ] [ PubMed]
  34. Paolisso G, Barbagallo M. Hypertension, diabetes mellitus, and insulin resistance: the role of intracellular magnesium. Am J Hypertens. 1997;10(3):346-55. [Crossref ]
  35. Ghose B, Ide S. Hypomagnesemia and type 2 diabetes mellitus: a review of the literature. Austin J Nutri Food Sci. 2014;2(4):1025.
  36. Tosiello L. Hypomagnesemia and diabetes mellitus: a review of clinical implications. Arch Intern Med. 1996;156(11):1143-8. [Crossref ] [PubMed]
  37. Schnack C, Bauer I, Pregant P, Hopmeier P, Schernthaner G. Hypomagnesaemia in type 2 (non-insulin-dependent) diabetes mellitus is not corrected by improvement of long-term metabolic control. Diabetologia. 1992;35(1): 77-9. [Crossref ] [PubMed]
  38. Wälti MK, Zimmermann MB, Walczyk T, Spinas GA, Hurrell RF. Measurement of magnesium absorption and retention in type 2 diabetic patients with the use of stable isotopes. Am J Clin Nutr. 2003;78(3):448-53. [Crossref ] [ PubMed]
  39. Guerrero-Romero F, Rodríguez-Morán M. Hypomagnesemia, oxidative stress, inflamma tion, and metabolic syndrome. Diabetes Metab Res Rev. 2006;22(6):471-6. [Crossref] [PubMed]
  40. Sales CH, Pedrosa LF, Lima JG, Lemos TM, Colli C. Influence of magnesium status and magnesium intake on the blood glucose control in patients with type 2 diabetes. Clin Nutr. 2011;30(3):359-64. [Crossref ] [PubMed]
  41. Prabodh S, Prakash D, Sudhakar G, Chowdary N, Desai V, Shekhar R. Status of copper and magnesium levels in diabetic nephropathy cases: a case-control study from South India. Biol Trace Elem Res. 2011;142(1):29-35. [Crossref ] [ PubMed]
  42. Nsonwu AC, Usoro CAO, Etukudo MH, Usoro IN. Serum and urine levels of chromium and magnesium in type 2 diabetics in Calabar, Nigeria. Malays J Nutr. 2005;11(2):133-42.
  43. Mooren FC, Krüger K, Völker K, Golf SW, Wadepuhl M, Kraus A. Oral magnesium supplementation reduces insulin resistance in non-diabetic subjects-a double-blind, placebo-controlled, randomized trial. Diabetes Obes Metab. 2011;13(3):281-4. [Crossref] [PubMed ]
  44. Song Y, He K, Levitan EB, Manson JE, Liu S. Effects of oral magnesium supplementation on glycaemic control in Type 2 diabetes: a meta-analysis of randomized double-blind controlled trials. Diabet Med. 2006;23(10):1050-6. [Crossref ] [PubMed]
  45. de Valk HW, Verkaaik R, van Rijn HJ, Geerdink RA, Struyvenberg A. Oral magnesium supplementation in insulin-requiring type 2 diabetic patients. Diabet Med.1998;15(6):503-7. [Crossref]
  46. de Lourdes Lima M, Cruz T, Pousada JC, Rodrigues LE, Barbosa K, Canguçu V. The effect of magnesium supplementation in increasing doses on the control of type 2 diabetes. Diabetes Care. 1998;21(5):682-6. [Crossref ] [PubMed]
  47. Guerrero-Romero F, Rodríguez -Morán M. Magnesium improves the beta-cell function to compensate variation of insulin sensitivity: double-blind, randomized clinical trial. Eur J Clin Invest. 2011;41(4):405-10. [Crossref] [PubMed ]
  48. Verma H, Garg R. Effect of magnesium supplementation on type 2 diabetes associated cardiovascular risk factors: a systematic re-view and meta-analysis. J Hum Nutr Diet. 2017;30(5):621-33. [Crossref ] [PubMed]
  49. Schwarz K, Mertz W. Chromium (III) and the glucose tolerance factor. Arch Biochem Biophys. 1959;85:292-5. [Crossref ]
  50. Ghosh D, Bhattacharya B, Mukherjee B, Manna B, Sinha M, Chowdhury J, et al. Role of chromium supplementation in Indians with type 2 diabetes mellitus. J Nutr Biochem. 2002;13(11):690-7. [Crossref ]
  51. Mita Y, Ishihara K, Ishiguro M, Takeda M, Hattori R, Murakami K, et al. Elevated urinary Cr loss induces a reduction in renal Cr concentration and the negative Cr balance in streptozotocin-induced diabetic mice. J Nutr Sci Vitaminol (Tokyo). 2008;54(4):303-8. [Crossref ]
  52. Doddigarla Z, Parwez I, Ahmad J. Correlation of serum chromium, zinc, magnesium and SOD levels with HbA1c in type 2 diabetes: a cross sectional analysis. Diabetes Metab Syndr. 2016;10(1 Suppl 1):S126-9. [Crossref ] [PubMed]
  53. Rajpathak S, Rimm EB, Li T, Morris JS, Stampfer MJ, Willett WC, et al. Lower toenail chromium in men with diabetes and cardiovascular disease compared with healthy men. Diabetes Care. 2004;27(9):2211-6. [Crossref ] [PubMed]
  54. Cefalu WT, Bell-Farrow AD, Stegner J, Wang ZQ, King T, Morgan T, et al. Effect of chromium picolinate on insulin sensitivity in vivo. The Journal of Trace Elements in Experimental Medicine. 1999;12(2):71-83. [Crossref]
  55. Kleefstra N, Houweling ST, Bakker SJ, Verhoeven S, Gans RO, Meyboom-de Jong B, et al. Chromium treatment has no effect in patients with type 2 diabetes in a Western population: a randomized, double-blind, placebo-controlled trial. Diabetes Care. 2007;30(5):1092-6. [Crossref ] [PubMed]
  56. Chen WY, Mao FC, Liu CH, Kuan YH, Lai NW, Wu CC, et al. Chromium supplementation improved post-stroke brain infarction and hyperglycemia. Metab Brain Dis. 2016;31(2):289-97. [Crossref] [PubMed]
  57. Ulas M, Orhan C, Tuzcu M, Ozercan IH, Sahin N, Gencoglu H, et al. Anti-diabetic potential of chromium histidinate in diabetic retinopathy rats. BMC Complement Altern Med. 2015;15:16. [Crossref] [PubMed] [PMC]
  58. San Mauro-Martin I, Ruiz-León AM, CaminaMartín M, Garicano-Vilar E, Collado-Yurrita L, Mateo-Silleras B, et al. [Chromium supplementation in patients with type 2 diabetes and high risk of type 2 diabetes: a meta-analysis of randomized controlled trials]. Nutr Hosp. 2016;33(1):27. [Crossref ] [PubMed]
  59. Abdollahi M, Farshchi A, Nikfar S, Seyedifar M. Effect of chromium on glucose and lipid profiles in patients with type 2 diabetes; a meta-analysis review of randomized trials. J Pharm Pharm Sci. 2013;16(1):99-114. [Crossref] [PubMed]
  60. Newsholme P, Cruzat VF, Keane KN, Carlessi R, de Bittencourt PI Jr. Molecular mechanisms of ROS production and oxidative stress in diabetes. Biochem J. 2016;473(24):4527-50. [Crossref] [PubMed]
  61. Liochev SI, Fridovich I. Mechanism of the peroxidase activity of Cu, Zn superoxide dismutase. Free Radic Biol Med. 2010;48(12):1565-9. [Crossref ] [ PubMed]
  62. Matough FA, Budin SB, Hamid ZA, Alwahaibi N, Mohamed J. The role of oxidative stress and antioxidants in diabetic complications. Sultan Qaboos Univ Med J. 2012;12(1):5-18. [Crossref] [PubMed] [PMC]
  63. Savu O, Ionescu-Tirgoviste C, Atanasiu V, Gaman L, Papacocea R, Stoian I. Increase in total antioxidant capacity of plasma despite high levels of oxidative stress in uncomplicated type 2 diabetes mellitus. J Int Med Res. 2012;40(2):709-16. [Crossref ] [PubMed]
  64. Viktorínová A, To?erová E, Križko M, Ďuračková Z. Altered metabolism of copper, zinc, and magnesium is associated with increased levels of glycated hemoglobin in patients with diabetes mellitus. Metabolism. 2009;58(10):1477-82. [Crossref ] [PubMed]
  65. Korc M. Manganese action on pancreatic protein synthesis in normal and diabetic rats. Am J Physiol. 1983;245(5 Pt 1):G628-34. [Crossref ] [PubMed]
  66. Everson GJ, Shrader RE. Abnormal glucose tolerance in manganese-deficient guinea pigs. J Nutr. 1968;94(1):89-94. [Crossref] [PubMed]
  67. Failla ML, Kiser RA. Altered tissue content and cytosol distribution of trace metals in experimental diabetes. J Nutr. 1981;111(11):19009. [Crossref ] [PubMed]
  68. Gouaref I, Bellahsene Z, Zekri S, Alamir B, Koceir EA. [The link between trace elements and metabolic syndrome/oxidative stress in essential hypertension with or without type 2 diabetes]. Ann Biol Clin (Paris). 2016;74(2):233-43.
  69. Hajra B, Orakzai BA, Faryal U, Hassan M, Rasheed S, Wazir S. Insulin sensitivity to trace metals (chromium, manganese) in type 2 diabetic patients and non diabetic individuals. J Ayub Med Coll Abbottabad. 2016;28(3):5346.
  70. Burlet E, Jain SK. Manganese supplementation increases adiponectin and lowers ICAM1 and creatinine blood levels in Zucker type 2 diabetic rats, and downregulates ICAM-1 by upregulating adiponectin multimerization protein (DsbA-L) in endothelial cells. Mol Cell Biochem. 2017;429(1-2):1-10. [Crossref] [PubMed]
  71. Lee SH, Jouihan HA, Cooksey RC, Jones D, Kim HJ, Winge DR, et al. Manganese supplementation protects against diet-induced diabetes in wild type mice by enhancing insulin secretion. Endocrinology. 2013;154(3):102938. [Crossref ] [PubMed] [PMC]
  72. Farina M, Avila DS, da Rocha JB, Aschner M. Metals, oxidative stress and neurodegeneration: a focus on iron, manganese and mercury. Neurochem Int. 2013;62(5):575-94. [Crossref] [PubMed] [PMC]
  73. Hatunic M, Finucane FM, Brennan AM, Norris S, Pacini G, Nolan JJ. Effect of iron overload on glucose metabolism in patients with hereditary hemochromatosis. Metabolism. 2010;59(3):380-4. [Crossref ] [PubMed]
  74. Sahay M, Kalra S, Badani R, Bantwal G, Bhoraskar A, Das AK, et al. Diabetes and anemia: International Diabetes Federation (IDF)Southeast Asian Region (SEAR) position statement. Diabetes Metab Syndr. 2017;11 Suppl 2:S685-S95. [Crossref] [PubMed]
  75. Fernández-Real JM, McClain D, Manco M. Mechanisms linking glucose homeostasis and iron metabolism toward the onset and progression of type 2 diabetes. Diabetes Care. 2015;38(11):2169-76. [Crossref ] [PubMed]
  76. Canturk Z, Cetinarslan B, Tarkun I, Canturk NZ. Serum ferritin levels in poorly and well-controlled diabetes mellitus. Endocr Res. 2003;29(3):299-306. [Crossref ] [PubMed]
  77. Rajpathak SN, Crandall JP, Wylie-Rosett J, Kabat GC, Rohan TE, Hu FB. The role of iron in type 2 diabetes in humans. Biochim Biophys Acta. 2009;1790(7):671-81. [Crossref] [PubMed]
  78. Howard RL, Buddington B, Alfrey AC. Urinary albumin, transferrin and iron excretion in diabetic patients. Kidney Int. 1991;40(5):923-6. [Crossref] [PubMed]
  79. Fernández-Real JM, López-Bermejo A, Ricart W. Cross-talk between iron metabolism and diabetes. Diabetes. 2002;51(8):2348-54. [Crossref] [PubMed]
  80. Wang N, Tan HY, Li S, Xu Y, Guo W, Feng Y. Supplementation of micronutrient selenium in metabolic diseases: its role as an antioxidant. Oxid Med Cell Longev. 2017;2017:747523. [Crossref] [PubMed] [ PMC]
  81. Mueller AS, Pallauf J. Compendium of the antidiabetic effects of supranutritional selenate doses. In vivo and in vitro investigations with type II diabetic db/db mice. J Nutr Biochem. 2006;17(8):548-60. [Crossref ] [PubMed]
  82. Becker D, Reul B, Ozcelikay AT, Buchet JP, Henquin JC, Brichard SM. Oral selenate improves glucose homeostasis and partly reverses abnormal expression of liver glycolytic and gluconeogenic enzymes in diabetic rats. Diabetologia. 1996;39(1):3-11. [Crossref] [PubMed]
  83. Kimura K. [Role of essential trace elements in the disturbance of carbohydrate metabolism]. Nihon Rinsho. 1996;54(1):79-84.
  84. Zhou J, Huang K, Lei XG. Selenium and diabetes--evidence from animal studies. Free Radic Biol Med. 2013;65:1548-56. [Crossref ] [PubMed] [PMC]
  85. Campbell SC, Aldibbiat A, Marriott CE, Landy C, Ali T, Ferris WF, et al. Selenium stimulates pancreatic beta-cell gene expression and en hances islet function. FEBS Lett. 2008;582(15):2333-7. [Crossref ] [PubMed]
  86. Fontenelle LC, Feitosa MM, Morais JBS, Severo JS, Freitas TEC, Beserra JB, et al. The role of selenium in insulin resistance. Braz J Pharm Sci. 2018;54(1):e00139. [Crossref ]
  87. Rayman MP, Blundell-Pound G, Pastor-Barriuso R, Guallar E, Steinbrenner H, Stranges S. A randomized trial of selenium supplementation and risk of type-2 diabetes, as assessed by plasma adiponectin. PloS One. 2012;7(9):e45269. [Crossref] [PubMed] [PMC]
  88. Laclaustra M, Stranges S, Navas-Acien A, Ordovas JM, Guallar E. Serum selenium concentrations and diabetes in US adults: National Health and Nutrition Examination Survey (NHANES) 2003-2004. Environ Health Perspect. 2009;117(9):1409-13. [Crossref] [PubMed] [PMC]
  89. Akbaraly TN, Arnaud J, Rayman MP, Hininger-Favier I, Roussel AM, Berr C, et al. Plasma selenium and risk of dysglycemia in an elderly French population: results from the prospective Epidemiology of Vascular Ageing Study. Nutr Metab (Lond). 2010;7(1):21. [Crossref ] [PubMed] [PMC]
  90. Wang XL, Yang TB, Wei J, Lei GH, Zeng C. Association between serum selenium level and type 2 diabetes mellitus: a non-linear dose?response meta-analysis of observational studies. Nutr J. 2015;15(1):48. [Crossref ] [PubMed] [PMC]
  91. Park K, Rimm EB, Siscovick DS, Spiegelman D, Manson JE, Morris JS, et al. Toenail selenium and incidence of type 2 diabetes mellitus in US men and women. Diabetes Care. 2012:35(7):1544-51. [Crossref] [PubMed] [PMC]
  92. Vinceti M, Grioni S, Alber D, Consonni D, Malagoli C, Agnoli C, et al. Toenail selenium and risk of type 2 diabetes: the ORDET cohort study. J Trace Elem Med Biol. 2015;29:145-50. [Crossref ] [PubMed]
  93. Mao S, Zhang A, Huang S. Selenium supplementation and the risk of type 2 diabetes mellitus: a meta-analysis of randomized controlled trials. Endocrince. 2014;47(3):758-63. [Crossref] [PubMed]
  94. Oztürk Z, Gurpinar T, Vural K, Boyacıoglu S, Korkmaz M, Var A. Effects of selenium on endothelial dysfunction and metabolic profile in low dose streptozotocin induced diabetic rats fed a high fat diet. Biotech Histochem. 2015;90(7):506-15. [Crossref ] [PubMed]
  95. Sheng XQ, Huang KX, Xu HB. New experimental observation on the relationship of selenium and diabetes mellitus. Biol Trace Elem Res. 2004;99(1-3):241-53. [Crossref]
  96. Satyanarayana S, Sekhar JR, Kumar KE, Shannika LB, Rajanna B, Rajanna S. Influence of selenium (antioxidant) on gliclazide induced hypoglycaemia/anti hyperglycaemia in normal/alloxan-induced diabetic rats. Mol Cell Biochem. 2006;283(1-2):123-7. [Crossref] [PubMed]
  97. Zhang G, Zhao Y, Liu F, Ling J, Lin J, Zhang C. Determination of essential and toxic elements in Cordyceps kyushuensis Kawam by inductively coupled plasma mass spectrometry. J Pharm Biomed Anal. 2013;72:172-6. [Crossref] [PubMed]
  98. Ramanadham S, Cros GH, Mongold JJ, Serrano JJ, McNeill JH. Enhanced in vivo sensitivity of vanadyl-treated diabetic rats to insulin. Can J Physiol Pharmacol. 1990;68(4):486-91. [Crossref] [PubMed]
  99. Brichard SM, Bailey CJ, Henquin JC. Marked improvement of glucose homeostasis in diabetic ob/ob mice given oral vanadate. Diabetes. 1990;39(11):1326-32. [Crossref] [PubMed]
  100. Orvig C, Thompson KH, Battell M, McNeill JH. Vanadium compounds as insulin mimics. Met Ions Biol Syst. 1995;31:575-94.
  101. Missaoui S, Ben Rhouma K, Yacoubi MT, Sakly M, Tebourbi O. Vanadyl sulfate treatment stimulates proliferation and regeneration of beta cells in pancreatic islets. J Diabetes Res. 2014;2014:540242. [Crossref] [PubMed] [PMC]
  102. Wang X, Sun T, Liu J, Shan Z, Jin Y, Chen S, et al. Inverse association of plasma vanadium levels with newly diagnosed type 2 diabetes in a Chinese population. Am J Epidemiol. 2014;180(4):378-84. [Crossref ] [PubMed]
  103. Cusi K, Cukier S, DeFronzo R, Torres M, Puchulu FM, Redondo JC. Vanadyl sulfate improves hepatic and muscle insulin sensitivity in type 2 diabetes. J Clin Endocrinol Metab. 2001;86(3):1410-7. [Crossref] [PubMed]
  104. Smith DM, Pickering RM, Lewith GT. A systematic review of vanadium oral supplements for glycaemic control in type 2 diabetes mellitus. QJM. 2008;101(5):351-8. [Crossref] [PubMed ]

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Ortadoğu Reklam Tanıtım Yayıncılık Turizm Eğitim İnşaat Sanayi ve Ticaret A.Ş.

.: Address

Turkocagi Caddesi No:30 06520 Balgat / ANKARA
Phone: +90 312 286 56 56
Fax: +90 312 220 04 70
E-mail: info@turkiyeklinikleri.com

.: Manuscript Editing Department

Phone: +90 312 286 56 56/ 2
E-mail: yaziisleri@turkiyeklinikleri.com

.: English Language Redaction

Phone: +90 312 286 56 56/ 145
E-mail: tkyayindestek@turkiyeklinikleri.com

.: Marketing Sales-Project Department

Phone: +90 312 286 56 56/ 142
E-mail: reklam@turkiyeklinikleri.com

.: Subscription and Public Relations Department

Phone: +90 312 286 56 56/ 118
E-mail: abone@turkiyeklinikleri.com

.: Customer Services

Phone: +90 312 286 56 56/ 118
E-mail: satisdestek@turkiyeklinikleri.com

1. TERMS OF USE

1.1. To use the web pages with http://www.turkiyeklinikleri.com domain name or the websites reached through the sub domain names attached to the domain name (They will be collectively referred as "SITE"), please read the conditions below. If you do not accept these terms, please cease to use the "SITE." "SITE" owner reserves the right to change the information on the website, forms, contents, the "SITE," "SITE" terms of use anytime they want.

1.2. The owner of the "SITE" is Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. (From now on it is going to be referred as "Turkiye Klinikleri", shortly) and it resides at Turkocagi cad. No:30, 06520 Balgat Ankara. The services in the "SITE" are provided by "Turkiye Klinikleri."

1.3. Anyone accessing the "SITE" with or without a fee whether they are a natural person or a legal identity is considered to agree these terms of use. In this contract hereby, "Turkiye Klinikleri" may change the stated terms anytime. These changes will be published in the "SITE" periodically and they will be valid when they are published. Any natural person or legal identity benefiting from and reaching to the "SITE" are considered to be agreed to any change on hereby contract terms done by "Turkiye Klinikleri."

1.4. The "Terms of Use" hereby is published in the website with the last change on March 30th 2014 and the "SITE" is activated by enabling the access to everyone. The "Terms of Use" hereby is also a part of the any "USER Contract" was and/or will be done with the users using "Turkiye Klinikleri" services with or without a fee an inseparable.

2. DEFINITIONS

2.1. "SITE": A website offering different kind of services and context with a certain frame determined by "Turkiye Klinikleri" and it is accessible on-line on http://www.turkiyeklinikleri.com domain name and/or subdomains connected to the domain name.

2.2. USER: A natural person or a legal identity accessing to the "SITE" through online settings.

2.3. LINK: A link enabling to access to another website through the "SITE", the files, the context or through another website to the "SITE", the files and the context.

2.4. CONTEXT: Any visual, literary and auditory images published in the "Turkiye Klinikleri", "SITE" and/or any website or any accessible information, file, picture, number/figures, price, etc.

2.5. "USER CONTRACT": An electronically signed contract between a natural or a legal identity benefiting from special services "Turkiye Klinikleri" will provide and "Turkiye Klinikleri".

3. SCOPE OF THE SERVICES

3.1. "Turkiye Klinikleri" is completely free to determine the scope and quality of the services via the "SITE".

3.2. To benefit the services of "Turkiye Klinikleri" "SITE", the "USER" must deliver the features that will be specified by "Turkiye Klinikleri". "Turkiye Klinikleri" may change this necessity any time single-sided.

3.3. Not for a limited number, the services "Turkiye Klinikleri" will provide through the "SITE" for a certain price or for free are;

- Providing scientific articles, books and informative publications for health industry.

- Providing structural, statistical and editorial support to article preparation stage for scientific journals.

4. GENERAL PROVISIONS

4.1. "Turkiye Klinikleri" is completely free to determine which of the services and contents provided in the "SITE" will be charged.

4.2. People benefiting from the services provided by "Turkiye Klinikleri" and using the website can use the "SITE" only according to the law and only for personal reasons. Users have the criminal and civil liability for every process and action they take in the "SITE". Every USER agrees, declares and undertakes that they will not proceed by any function or action infringement of rights of "Turkiye Klinikleri"s and/or other third parties', they are the exclusive right holder on usage, processing, storage, made public and revealing any written, visual or auditory information reported to Turkiye Klinikleri" and/or "SITE" to the third parties. "USER" agrees and undertakes that s/he will not duplicate, copy, distribute, process, the pictures, text, visual and auditory images, video clips, files, databases, catalogs and lists within the "SITE", s/he will not be using these actions or with other ways to compete with "Turkiye Klinikleri", directly or indirectly.

4.3. The services provided and the context published within the "SITE" by third parties is not under the responsibility of "Turkiye Klinikleri", institutions collaborated with "Turkiye Klinikleri", "Turkiye Klinikleri" employee and directors, "Turkiye Klinikleri" authorized salespeople. Commitment to accuracy and legality of the published information, context, visual and auditory images provided by any third party are under the full responsibility of the third party. "Turkiye Klinikleri" does not promise and guarantee the safety, accuracy and legality of the services and context provided by a third party.

4.4. "USER"s cannot act against "Turkiye Klinikleri", other "USER"s and third parties by using the "SITE". "Turkiye Klinikleri" has no direct and/or indirect responsibility for any damage a third party suffered or will suffer regarding "USER"s actions on the "SITE" against the rules of the hereby "Terms of Use" and the law.

4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com