Serum Zinc, Copper and Ceruloplasmin Levels in Type 2 Diabetic Patients

Year 2021, Volume: 3 Issue: 1, 1 - 9, 30.04.2021

Emine Şen Bayram Şen Özge Paşaoğlu Müjde Aktürk Işılay Kalan Sarı , Bülent Çelik , Hatice Pasaoglu

Abstract

Our objective was to investigate the possible alterations in serum zinc, copper and ceruloplasmin levels in type 2 diabetes. Fifty patients with type 2 diabetes mellitus (23 male, 27 female) who were being treated and followed by Gazi University Internal Medicine Obesity and Diabetes Clinic and 30 healthy volunteers (12 male, 18 female) were included in the study. Serum zinc and copper levels were measured by atomic absorption spectroscopy and ceruloplasmin oxidase activity was determined spectrophotometrically. While zinc levels of female diabetics were found to be significantly lower than female control group, there were no significant differences neither between male patients and male controls, nor between patient group and control group. There was no statistically significant difference in serum copper levels between patient and control groups. However, in both groups, copper levels of female subjects were found significantly higher than males. Ceruloplasmin oxidase activities were higher in patient group compared with controls and both in male and female patient groups compared with their respective controls. There was a positive correlation between serum copper and ceruloplasmin oxidase activity. These results imply that serum ceruloplasmin oxidase activity in type 2 diabetic patients and zinc levels in female type 2 diabetics show important alterations.

Keywords

Zinc, Copper, Ceruloplasmin oxidase, Type 2 Diabetes Mellitus

References

• Al-Maroof, R. A., & Al-Sharbatti, S. S. (2006). Serum zinc levels in diabetic patients and effect of zinc supplementation on glycemic control of type 2 diabetics. Saudi Med J, 27(3), 344-350.
• Arslan, M. (1996). Obezite. In S. Koloğlu (Ed.), Endokrinoloji Temel ve Klinik (pp. 775-787). Ankara: Medical Network.
• Atari-Hajipirloo, S., Valizadeh, N., Khadem-Ansari, M. H., Rasmi, Y., & Kheradmand, F. (2016). Altered Concentrations of Copper, Zinc, and Iron are Associated With Increased Levels of Glycated Hemoglobin in Patients With Type 2 Diabetes Mellitus and Their First-Degree Relatives. Int J Endocrinol Metab, 14(2), e33273. doi:10.5812/ijem.33273
• Azevedo, M., Fernandes, F., Lisboa, P., Fontes, G., & Manso, C. (1980). Serum copper, ceruloplasmin and monoamine oxidase in diabetics with different times of evolution of the disease. Acta Med Port, 2(2), 107-112.
• Beletate, V., El Dib, R. P., & Atallah, A. N. (2007). Zinc supplementation for the prevention of type 2 diabetes mellitus. Cochrane Database Syst Rev(1), Cd005525. doi:10.1002/14651858.CD005525.pub2
• Brunton, S. (2016). Pathophysiology of Type 2 Diabetes: The Evolution of Our Understanding. J Fam Pract, 65(4 Suppl).
• Burant, C. F. (2004). Medical Management of Type Two Diabetes (C. F. Burant Ed. 5 ed.): American Diabetes Association.
• Daimon, M., Susa, S., Yamatani, K., Manaka, H., Hama, K., Kimura, M., . . . Kato, T. (1998). Hyperglycemia is a factor for an increase in serum ceruloplasmin in type 2 diabetes. Diabetes Care, 21(9), 1525-1528. doi:10.2337/diacare.21.9.1525
• El-Zebda, G. A. (2006). Significance of Serum Levels of Copper and Zinc in Type 2 Diabetic, Hypertensive and Diabetic Hypertensive Patients in Gaza City. (Master Master Thesis). The Islamic University of Gaza, Gaza.
• Fox, P. L., Mukhopadhyay, C., & Ehrenwald, E. (1995). Structure, oxidant activity, and cardiovascular mechanisms of human ceruloplasmin. Life Sci, 56(21), 1749-1758. doi:10.1016/0024-3205(95)00146-w
• Garber, A. J. (2000). The importance of early insulin secretion and its impact on glycaemic regulation. Int J Obes Relat Metab Disord, 24 Suppl 3, S32-37. doi:10.1038/sj.ijo.0801423
• Gödény, S., Borbély-Kiss, I., Koltay, E., László, S., & Szabó, G. (1986). Determination of trace and bulk elements in plasma and erythrocytes of diabetic pregnant women by PIXE method. Int J Gynaecol Obstet, 24(3), 201-207. doi:10.1016/0020-7292(86)90098-6
• Grace, N. D., & Lee, J. (1990). Effect of Co, Cu, Fe, Mn, Mo, Se, and Zn supplementation on the elemental content of soft tissues and bone in sheep grazing ryegrass/white clover pasture. New Zealand Journal of Agricultural Research, 33(4), 635-647. doi:10.1080/00288233.1990.10428468
• Halaçoğlu, A., & Suher, M. (2012). Diabetes Mellitus Regülasyonunun Serum Eser Elementleri ile İlişkisi. Yeni Tıp Dergisi, 29(1), 47-49.
• Huma, Y., Yahya, K. M., & Saqib, A. (2011). Minerals and type 2 diabetes mellitus-level of Zinc, Magnesium and Chromium in diabetic and nondiabetic population. JUMDC, 2(1), 34-38.
• Kinlaw, W. B., Levine, A. S., Morley, J. E., Silvis, S. E., & McClain, C. J. (1983). Abnormal zinc metabolism in type II diabetes mellitus. Am J Med, 75(2), 273-277. doi:10.1016/0002-9343(83)91205-6
• Kurtul, N., Pençe, S., Çil, M. Y., Aksoy, H., & Erman, F. (2007). Tip 2 Diabetes Mellituslularda Serum Çinko ve Bakır Değerleri ile Cinsiyet ve Yaş Arasındaki İlişki. Gaziantep Tıp Dergisi, 13(2), 7-12.
• Masood, N., Baloch, G. H., Ghori, R. A., Memon, I. A., Memon, M. A., & Memon, M. S. (2009). Serum zinc and magnesium in type-2 diabetic patients. J Coll Physicians Surg Pak, 19(8), 483-486.
• Mateescu, M. A., Chahine, R., Roger, S., Atanasiu, R., Yamaguchi, N., Lalumière, G., & Nadeau, R. (1995). Protection of myocardial tissue against deleterious effects of oxygen free radicals by ceruloplasmin. Arzneimittelforschung, 45(4), 476-480.
• Memişoğullari, R., & Bakan, E. (2004). Levels of ceruloplasmin, transferrin, and lipid peroxidation in the serum of patients with Type 2 diabetes mellitus. J Diabetes Complications, 18(4), 193-197. doi:10.1016/s1056-8727(03)00032-1
• Newman, B., Selby, J. V., King, M. C., Slemenda, C., Fabsitz, R., & Friedman, G. D. (1987). Concordance for type 2 (non-insulin-dependent) diabetes mellitus in male twins. Diabetologia, 30(10), 763-768. doi:10.1007/bf00275741
• Nielsen, S. H., Jensen, J. E., & Magid, E. (1994). Episodic albuminuria in acute ischaemic heart disease. Lancet, 343(8899), 732. doi:10.1016/s0140-6736(94)91611-x
• Nobels, F., Rillaerts, E., D'Hollander, M., Van Gaal, L., & De Leeuw, I. (1986). Plasma zinc levels in diabetes mellitus: relation to plasma albumin and amino acids. Biomed Pharmacother, 40(2), 57-60.
• Olaniyan, O. O., Awonuga, M. A. M., Ajetunmobi, A. F., Adeleke, I. A., Fagbolade, O. J., Olabiyi, K. O., . . . Osadolor, H. B. (2012). Serum Copper and Zinc Levels in Nigerian Type 2 Diabetic Patients. African Journal of Diabetes Medicine, 20(2), 36-38.
• Pham, P. C., Pham, P. M., Pham, S. V., Miller, J. M., & Pham, P. T. (2007). Hypomagnesemia in patients with type 2 diabetes. Clin J Am Soc Nephrol, 2(2), 366-373. doi:10.2215/cjn.02960906
• Pollard, B. D. (1981). Principles of Instrumental Analysis (Skoog, D. A.; West, D. M.). Journal of Chemical Education, 58(10), A314. doi:10.1021/ed058pA314.2
• Powers, A. C. (2008). Diabetes Mellitus. In A. S. Fauci, D. L. Kasper, D. L. Longo, E. Braunwald, H. S. L., J. J. L., & L. J. (Eds.), Harrison’s Principles of Internal Medicine (17 ed.). USA: McGraw-Hill Medical.
• Prasad, A. S. (2013). Discovery of human zinc deficiency: its impact on human health and disease. Adv Nutr, 4(2), 176-190. doi:10.3945/an.112.003210
• Raudenska, M., Dvorakova, V., Pacal, L., Chalasova, K., Kratochvilova, M., Gumulec, J., . . . Masarik, M. (2017). Levels of heavy metals and their binding protein metallothionein in type 2 diabetics with kidney disease. J Biochem Mol Toxicol, 31(6). doi:10.1002/jbt.21891
• Rehman, K., & Akash, M. S. H. (2017). Mechanism of Generation of Oxidative Stress and Pathophysiology of Type 2 Diabetes Mellitus: How Are They Interlinked? J Cell Biochem, 118(11), 3577-3585. doi:10.1002/jcb.26097
• Rusu, M. L., MăruŃoiu, C., Rusu, L. D., MăruŃoiu, O. F., HoŃoleanu, C., & Poantă, L. (2001). Testing of Magnesium, Zinc and Copper Blood Levels in Diabetes Mellitus Patients Acta Universitatis Cibiniensis Seria F Chemia, 8(2), 61-63.
• Sanjeevi, N., Freeland-Graves, J., Beretvas, S. N., & Sachdev, P. K. (2018). Trace element status in type 2 diabetes: A meta-analysis. J Clin Diagn Res, 12(5), Oe01-oe08. doi:10.7860/jcdr/2018/35026.11541
• Sarkar, A., Dash, S., Barik, B. K., Muttigi, M. S., Kedage, V., Shetty, J. K., & Prakash, M. (2010). Copper and ceruloplasmin levels in relation to total thiols and GST in type 2 diabetes mellitus patients. Indian J Clin Biochem, 25(1), 74-76. doi:10.1007/s12291-010-0015-0
• Satman, I., Yilmaz, T., Sengül, A., Salman, S., Salman, F., Uygur, S., . . . King, H. (2002). Population-based study of diabetes and risk characteristics in Turkey: results of the turkish diabetes epidemiology study (TURDEP). Diabetes Care, 25(9), 1551-1556. doi:10.2337/diacare.25.9.1551
• Shukla, N., Maher, J., Masters, J., Angelini, G. D., & Jeremy, J. Y. (2006). Does oxidative stress change ceruloplasmin from a protective to a vasculopathic factor? Atherosclerosis, 187(2), 238-250. doi:10.1016/j.atherosclerosis.2005.11.035
• Sinha, S., & Sen, S. (2014). Status of zinc and magnesium levels in type 2 diabetes mellitus and its relationship with glycemic status. International Journal of Diabetes in Developing Countries, 34(4), 220-223. doi:10.1007/s13410-014-0196-9
• Skalnaya, M. G., Skalny, A. V., & Tinkov, A. A. (2017). Serum copper, zinc, and iron levels, and markers of carbohydrate metabolism in postmenopausal women with prediabetes and type 2 diabetes mellitus. J Trace Elem Med Biol, 43, 46-51. doi:10.1016/j.jtemb.2016.11.005
• Sunderman, F. W., Jr., & Nomoto, S. (1970). Measurement of human serum ceruloplasmin by its p-phenylenediamine oxidase activity. Clin Chem, 16(11), 903-910.
• Supriya, M. S., Pinnelli, V. B., Murgod, R., & Raghavendra, D. S. (2013). Evaluation of serum copper, magnesium and glycated haemoglobin in type 2 diabetes mellitus. Asian Journal of Pharmaceutical and Clinical Research, 6(2), 188-190.
• Uusitupa, M. I., Niskanen, L. K., Siitonen, O., Voutilainen, E., & Pyörälä, K. (1993). Ten-year cardiovascular mortality in relation to risk factors and abnormalities in lipoprotein composition in type 2 (non-insulin-dependent) diabetic and non-diabetic subjects. Diabetologia, 36(11), 1175-1184. doi:10.1007/bf00401063
• Vallee, B. L., & Falchuk, K. H. (1993). The biochemical basis of zinc physiology. Physiol Rev, 73(1), 79-118. doi:10.1152/physrev.1993.73.1.79
• Viktorínová, A., Toserová, E., Krizko, M., & Duracková, Z. (2009). Altered metabolism of copper, zinc, and magnesium is associated with increased levels of glycated hemoglobin in patients with diabetes mellitus. Metabolism, 58(10), 1477-1482. doi:10.1016/j.metabol.2009.04.035
• Walter, R. M., Jr., Uriu-Hare, J. Y., Olin, K. L., Oster, M. H., Anawalt, B. D., Critchfield, J. W., & Keen, C. L. (1991). Copper, zinc, manganese, and magnesium status and complications of diabetes mellitus. Diabetes Care, 14(11), 1050-1056. doi:10.2337/diacare.14.11.1050
• Zhang, H., Yan, C., Yang, Z., Zhang, W., Niu, Y., Li, X., . . . Su, Q. (2017). Alterations of serum trace elements in patients with type 2 diabetes. J Trace Elem Med Biol, 40, 91-96. doi:10.1016/j.jtemb.2016.12.017
• Zimmet, P. Z. (1992). Kelly West Lecture 1991. Challenges in diabetes epidemiology--from West to the rest. Diabetes Care, 15(2), 232-252. doi:10.2337/diacare.15.2.232