This study investigated the association of copper and zinc levels in the serum or urine of patients living in northeast China, with either prediabetes or diabetes. From January 2010 to October 2011, patients with type 1 diabetes (T1D, ), type 2 diabetes (T2D, ), impaired fasting glucose (IFG, ) or impaired glucose tolerance (IGT, ), and age/gender matched controls ( ) were enrolled. In the T2D group, there were 24 patients with nephropathy, 34 with retinopathy, and 50 with peripheral neuropathy. Serum copper levels were significantly higher in IFG, IGT, and T2D groups. Serum zinc level was dramatically lower, and urinary zinc level was significantly higher in both T1D and T2D subjects compared with controls. The serum zinc/copper ratio was significantly lower in all the patients with IFG, ITG, T1D, and T2D. The serum copper level was positively associated with HbA1c in T2D subjects. Simvastatin treatment in T2D patients had no significant effect on serum and urinary copper and zinc. These results suggest the need for further studies of the potential impact of the imbalanced serum copper and zinc levels on metabolic syndrome, diabetes, and diabetic complications. 1. Introduction Diabetes has become a pandemic disease. According to the International Diabetes Federation, diabetes affects at least 285 million people worldwide, and this number is expected to reach 438 million by the year 2030 [1]. The number of adults with impaired glucose tolerance will rise from 344 million in 2010 to an estimated 472 million by 2030 [1]. The prevalence of diabetes in China has increased dramatically in recent decades. In 1980, less than 1% of Chinese adults had this disease. By 2008, the prevalence had reached nearly 10% [1, 2]. It was estimated that more than 92 million Chinese adults had diabetes and another 148 million were prediabetic [2]. The threatening effect of diabetes for these patients is chronic hyperglycemia induced microvascular complications such as diabetic retinopathy, neuropathy, and nephropathy [2]. Excessive caloric intake and high-energy diet quality are major driving forces behind escalating diabetes and the appearance of epidemics worldwide [1, 3]. As an essential component of the daily diet intake, trace elements are also important for the pathogenesis of diabetes and diabetic complications. Disturbances in trace element status and increased oxidative stress in diabetes may contribute to insulin resistance and the development of diabetes and diabetic complications [4, 5]. On the other hand, progression of diabetes may also lead to perturbation in
References
[1]
F. B. Hu, “Globalization of diabetes: the role of diet, lifestyle, and genes,” Diabetes Care, vol. 34, no. 6, pp. 1249–1257, 2011.
[2]
W. Yang, J. Lu, J. Weng et al., “Prevalence of diabetes among men and women in China,” The New England Journal of Medicine, vol. 362, no. 12, pp. 1090–1101, 2010.
[3]
F. B. Hu, J. E. Manson, M. J. Stampfer et al., “Diet, lifestyle, and the risk of type 2 diabetes mellitus in women,” The New England Journal of Medicine, vol. 345, no. 11, pp. 790–797, 2001.
[4]
M. Friederich, P. Hansell, and F. Palm, “Diabetes, oxidative stress, nitric oxide and mitochondria function,” Current Diabetes Reviews, vol. 5, no. 2, pp. 120–144, 2009.
[5]
Z. Cheng, Y. Tseng, and M. F. White, “Insulin signaling meets mitochondria in metabolism,” Trends in Endocrinology and Metabolism, vol. 21, no. 10, pp. 589–598, 2010.
[6]
A. Viktorínová, E. To？erová, M. Kri？ko, and Z. ？ura？ková, “Altered metabolism of copper, zinc, and magnesium is associated with increased levels of glycated hemoglobin in patients with diabetes mellitus,” Metabolism, vol. 58, no. 10, pp. 1477–1482, 2009.
[7]
B. Li, Y. Tan, W. Sun, Y. Fu, L. Miao, and L. Cai, “The role of zinc in the prevention of diabetic cardiomyopathy and nephropathy,” Toxicol Mech Methods, vol. 23, no. 1, pp. 27–33, 2013.
[8]
B. Li, S. Liu, L. Miao, and L. Cai, “Prevention of diabetic complications by activation of Nrf2: diabetic cardiomyopathy and nephropathy,” Experimental Diabetes Research, vol. 2012, Article ID 216512, 7 pages, 2012.
[9]
Q. Liu, L. Sun, Y. Tan, G. Wang, X. Lin, and L. Cai, “Role of iron deficiency and overload in the pathogenesis of diabetes and diabetic complications,” Current Medicinal Chemistry, vol. 16, no. 1, pp. 113–129, 2009.
[10]
L. Sun, O. H. Franco, F. B. Hu et al., “Ferritin concentrations, metabolic syndrome, and type 2 diabetes in middle-aged and elderly Chinese,” Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 12, pp. 4690–4696, 2008.
[11]
L. Sun, Y. Yu, T. Huang et al., “Associations between ionomic profile and metabolic abnormalities in human population,” PLoS ONE, vol. 7, no. 6, Article ID e38845, 2012.
[12]
Y. Zheng, X.-K. Li, Y. Wang, and L. Cai, “The role of zinc, copper and iron in the pathogenesis of diabetes and diabetic complications: therapeutic effects by chelators,” Hemoglobin, vol. 32, no. 1-2, pp. 135–145, 2008.
[13]
R. A. DiSilvestro, “Zinc in relation to diabetes and oxidative disease,” Journal of Nutrition, vol. 130, supplement 5, pp. 109S–1511S, 2000.
[14]
J. M. Forbes, M. T. Coughlan, and M. E. Cooper, “Oxidative stress as a major culprit in kidney disease in diabetes,” Diabetes, vol. 57, no. 6, pp. 1446–1454, 2008.
[15]
R. M. Walter Jr., J. Y. Uriu-Hare, K. L. Olin et al., “Copper, zinc, manganese, and magnesium status and complications of diabetes mellitus,” Diabetes Care, vol. 14, no. 11, pp. 1050–1056, 1991.
[16]
C. M. Galhardi, Y. S. Diniz, L. A. Faine et al., “Toxicity of copper intake: Lipid profile, oxidative stress and susceptibility to renal dysfunction,” Food and Chemical Toxicology, vol. 42, no. 12, pp. 2053–2060, 2004.
[17]
J. Xu, W. Xu, H. Yao, W. Sun, Q. Zhou, and L. Cai, “Associations of serum and urinary magnesium with the pre-diabetes, diabetes and diabetic complications in the Chinese Northeast population,” PLoS ONE, vol. 8, no. 2, Article ID e56750, 2013.
[18]
D. Leibowitz, J. M. Jacobs, I. Stessman-Lande et al., “Cardiac structure and function and dependency in the oldest old,” Journal of the American Geriatrics Society, vol. 59, no. 8, pp. 1429–1434, 2011.
[19]
S. Faber, G. M. Zinn, J. C. Kern II, and H. M. Skip Kingston, “The plasma zinc/serum copper ratio as a biomarker in children with autism spectrum disorders,” Biomarkers, vol. 14, no. 3, pp. 171–180, 2009.
[20]
J. George, V. N. Bhatia, S. Balakrishnan, and G. Ramu, “Serum zinc/copper ratio in subtypes of leprosy and effect of oral zinc therapy on reactional states,” International Journal of Leprosy, vol. 59, no. 1, pp. 20–24, 1991.
[21]
T. Naka, H. Kaneto, N. Katakami et al., “Association of serum copper levels and glycemic control in patients with type 2 diabetes,” Endocrine Journal, vol. 60, no. 3, pp. 393–396, 2013.
[22]
A. H. Zargar, N. A. Shah, S. R. Masoodi et al., “Copper, zinc, and magnesium levels in non-insulin dependent diabetes mellitus,” Postgraduate Medical Journal, vol. 74, no. 877, pp. 665–668, 1998.
[23]
M. C. M. Mateo, J. B. Bustamante, and M. A. G. Cantalapiedra, “Serum zinc copper and insulin in diabetes mellitus,” Biomedicine Express, vol. 29, no. 2, pp. 56–58, 1978.
[24]
M. Basaki, M. Saeb, S. Nazifi, and H. A. Shamsaei, “Zinc, copper, iron, and chromium concentrations in young patients with type 2 diabetes mellitus,” Biological Trace Element Research, vol. 148, pp. 161–164, 2012.
[25]
S. Ferdousi and A. R. Mia, “Serum levels of copper and zinc in newly diagnosed type-2 diabetic subjects,” Mymensingh Medical Journal, vol. 21, no. 3, pp. 475–478, 2012.
[26]
T. Isbir, L. Tamer, A. Taylor, and M. Isbir, “Zinc, copper and magnesium status in insulin-dependent diabetes,” Diabetes Research, vol. 26, no. 1, pp. 41–45, 1994.
[27]
M. Estakhri, A. Djazayery, M. R. Eshraghian et al., “Serum zinc levels in children and adolescents with type-1 diabetes mellitus,” Iranian Journal of Public Health, vol. 40, no. 4, pp. 83–88, 2011.
[28]
A. Bideci, M. O. ？amurdan, P. Cinaz, H. Dursun, and F. Demirel, “Serum zinc, insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels in children with type 1 diabetes mellitus,” Journal of Pediatric Endocrinology and Metabolism, vol. 18, no. 10, pp. 1007–1011, 2005.
[29]
C. Terres-Martos, M. Navarro-Alarcon, F. Martin-Lagos, et al., “Serum zinc and copper concentrations and Cu/Zn ratios in patients with hepatopathies or diabetes,” Journal of Trace Elements in Medicine and Biology, vol. 12, no. 1, pp. 44–49, 1998.
[30]
T. Tuvemo and M. Gebre-Medhin, “The role of trace elements in juvenile diabetes mellitus,” Pediatrician, vol. 12, no. 4, pp. 213–219, 1983.
[31]
A. Talaei, S. Jabari, M. H. Bigdeli, H. Farahani, and M. Siavash, “Correlation between microalbuminuria and urinary copper in type two diabetic patients,” Indian Journal of Endocrinology and Metabolism, vol. 15, no. 4, pp. 316–319, 2011.
[32]
C. R. Flores, M. P. Puga, K. Wrobel, M. E. Garay Sevilla, and K. Wrobel, “Trace elements status in diabetes mellitus type 2: possible role of the interaction between molybdenum and copper in the progress of typical complications,” Diabetes Research and Clinical Practice, vol. 91, no. 3, pp. 333–341, 2011.
[33]
S. Caner Karahan, O. De？er, A. ？rem et al., “The effects of impaired trace element status on polymorphonuclear leukocyte activation in the development of vascular complications in type 2 diabetes mellitus,” Clinical Chemistry and Laboratory Medicine, vol. 39, no. 2, pp. 109–115, 2001.
[34]
N. Car, A. Car, M. Granic, Z. Skrabalo, and B. Momcilovic, “Zinc and copper in the serum of diabetic patients,” Biological Trace Element Research, vol. 32, pp. 325–329, 1992.
[35]
L. Cai, X.-K. Li, Y. Song, and M. G. Cherian, “Essentiality, toxicology and chelation therapy of zinc and copper,” Current Medicinal Chemistry, vol. 12, no. 23, pp. 2753–2763, 2005.
[36]
G. J. Cooper, “Selective divalent copper chelation for the treatment of diabetes mellitus,” Current Medicinal Chemistry, vol. 19, no. 17, pp. 2828–2860, 2012.
[37]
G. J. S. Cooper, Y.-K. Chan, A. M. Dissanayake et al., “Demonstration of a hyperglycemia-driven pathogenic abnormality of copper homeostasis in diabetes and its reversibility by selective chelation: quantitative comparisons between the biology of copper and eight other nutritionally essential elements in normal and diabetic individuals,” Diabetes, vol. 54, no. 5, pp. 1468–1476, 2005.
[38]
J. Lu, D. Gong, S. Y. Choong et al., “Copper(II)-selective chelation improves function and antioxidant defences in cardiovascular tissues of rats as a model of diabetes: comparisons between triethylenetetramine and three less copper-selective transition-metal-targeted treatments,” Diabetologia, vol. 53, no. 6, pp. 1217–1226, 2010.
[39]
S. J. L. Bakker, G. Navis, and R. O. B. Gans, “Copper chelation as a potential treatment for left-ventricular hypertrophy in type 2 diabetes,” Diabetologia, vol. 52, no. 10, p. 2244, 2009.
[40]
G. J. S. Cooper, A. R. J. Phillips, S. Y. Choong et al., “Regeneration of the heart in diabetes by selective copper chelation,” Diabetes, vol. 53, no. 9, pp. 2501–2508, 2004.
[41]
J. S. Skyler, “Diabetic complications: the importance of glucose control,” Endocrinology and Metabolism Clinics of North America, vol. 25, no. 2, pp. 243–254, 1996.
[42]
E. P. O'Sullivan and S. F. Dinneen, “Benefits of early intensive glucose control to prevent diabetes complications were sustained for up to 10 years,” Evidence-Based Medicine, vol. 14, no. 1, pp. 9–10, 2009.
[43]
T. K. Mattila and A. De Boer, “Influence of intensive versus conventional glucose control on microvascular and macrovascular complications in type 1 and 2 diabetes mellitus,” Drugs, vol. 70, no. 17, pp. 2229–2245, 2010.
[44]
C. H. Zhu, S. S. Zhang, Y. Kong, Y. F. Bi, L. Wang, and Q. Zhang, “Effects of intensive control of blood glucose and blood pressure on microvascular complications in patients with type II diabetes mellitus,” International Ophthalmology, vol. 6, no. 2, pp. 141–145, 2013.
[45]
M. Ghayour-Mobarhan, D. J. Lamb, A. Taylor et al., “Effect of statin therapy on serum trace element status in dyslipidaemic subjects,” Journal of Trace Elements in Medicine and Biology, vol. 19, no. 1, pp. 61–67, 2005.
