Current Understanding of the Relationship between Metal Exposures and Risk of Type 2 Diabetes
Tongzhang Zheng1,2*, Simin Liu1, Yana Bai2, Ning Cheng2, Stephone Buka1, Aimin Yang1, Kunchong Shi1, Xichi Zhang3, Yuanyuan Li4, Shunqing Xu4, Bin Zhang5 and John Wise6
1Department of Epidemiology, Brown University School of Public Health, USA
2Department of Epidemiology, Lanzhou University School of Public Health, China
3The George Washington University, USA
4State Key Laboratory of Environmental Health, School of Public Health, China
5Wuhan Women and Children Medical Care Center, China
6Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, USA
Submission: January 22, 2018; Published: May 22, 2018
*Corresponding author: Tongzhang Zheng, Department of Epidemiology, Brown University School of Public Health, 121 South Main Street, Providence, RI 02903, USA, Tel: 401-863-6365; Email: tongzhang_zheng@brown.edu
How to cite this article: Tongzhang Z, Simin L, Yana B, Ning C, Stephone B. et al Current Understanding of the Relationship between Metal Exposures and Risk of Type 2 Diabetes. Curre Res Diabetes & Obes J. 2018; 7(2): 555710. DOI: 10.19080/CRDOJ.2018.07.555710.
Introduction
Type 2 diabetes (T2D) and its complications constitute a major public health problem for both developed and developing countries due to the high rate of morbidity and mortality associated with the disease. More than 400 million people worldwide have T2D, and there has been a rapid increase globally in its burden [1]. In the U.S., the Centers for Disease Control and Prevention reported that 29 million people have diabetes [2] and one in three children born in the US in the year 2000 will go on to develop T2D at some point in their lifetime [3]. In China, a recent national survey reported up to 114 million Chinese adults with T2D [4]. Thus, identification of novel preventable risk factors for T2D beyond those that are already established is an urgent need with significant public health implications. New evidence from both experimental and human studies has resulted in increased interest in studying the relationship between T2D and heavy metal exposures that are ubiquitous in the environment. A heavy metal is any metal or metalloid of environmental health concern, including both toxic metals and essential trace metals. Due to large-scale production and consumption, heavy metals are emitted into the environment in large quantities through solid waste and wastewater disposal, recycling of electronic and electric waste, vehicle exhausts and industrial pollution. Human exposure to heavy metals occurs through inhalation of dust, direct ingestion of polluted soil and water, dermal contact of contaminated soil and water, and consumption of foods grown in contaminated fields as well as tobacco products. Below is a brief review of the current understanding of the relationship between metal exposures and risk of type 2 diabetes and the suggestions for future studies.
Proposed mechanisms linking heavy metal to T2D risk
If heavy metal exposures indeed increase T2D risk, then, how do they affect the risk? The current literature does not seem to allow us to draw a definitive conclusion. Seven potential mechanisms are briefly summarized below. It should be noted that individual heavy metals may increase T2D risk via different biological mechanisms due to the fact that 1) specific toxic metals have varied toxicities in pancreatic islet cells [5-7], 2) essential trace metals at normal levels have varied biological functionsthatare directly involved in glucose homeostasis [7-9], and 3) imbalances of essential trace metals in humanshave different impacts on islet cells and diabetogenic effects [8-10]. Multiple mechanisms may also be involved to work synergistically resulting in islet dysfunction and ultimately dysglycemia [10]. Pancreatic islet β-cell dysfunction and insulin resistance are the hallmark of T2D, and thus heavy metals that reduce the function of insulin producing β-cells are therefore highly relevant to T2D risk.
Toxic metals-induced oxidative stress directly damage pancreatic islet β-cells:It is well known that toxic metals (As, Cd, Hg, Pb) have the ability to induce oxidative stress through the increased production of reactive oxygen species (ROS) such as superoxide radicals, hydrogen peroxide and nitric oxide that are highly reactive [11,12]. The islet β-cells have a high expression of metal transporters and low expression of antioxidants that creates a weak anti-oxidative defense system in pancreatic islet cells that makes the islet cells extremely sensitive to the effects of heavy metals, resulting in pancreatic islet β-cell dysfunction or destruction or even death [6]. Studies have shown that as increases ROS generation and induces oxidative stress and cell death in pancreatic β-cells [12-14]. Cd can accumulate in pancreatic β-cells and cause β-cell dysfunction, induce degeneration, necrosis, and weak degranulation in the β-cells and decrease β-cell viability and even induce β-cell death through induction of oxidative stress and disruption of islet β-cell function [10,15-17]. The toxicity of Hg in islets is highly related to oxidative stress [18] since Hg-induced oxidative stress can cause islet β-cell dysfunction, apoptosis and death [19-21]. Pb is known to induce production of ROS [12,22,23] and Pb-triggered oxidative stress can lead to the degradation of proteins, nucleic acids and lipid peroxidation [22]. Exposure to Ni, which is considered both toxic and essential metal, also causes production of free radicals impairing islet function and induces glucose deregulation [24-28].
Toxic metal-induced oxidative stress affects insulin gene activities:Toxic metal-induced oxidative stress could also decrease insulin gene promoter activity and insulin mRNA expression in pancreatic islet β-cells [6,7,12,29,30] and, thus, alter the related molecular mechanism in glucose regulations and modify their functions and kinetics by decreasing insulin release; impairing insulin receptor and disrupting the glucose uptake; decreasing peripheral utilization of glucose and inducing gluconeogenesis; increasing hepatic glycolysis and pancreatic glucagon release [6,7,12,31-34]. Hence, the toxic metal exposure and the resulting oxidative attack in insulin gene activity could be an important factor in the pathogenesis of T2D.
Imbalanced body levels of essential trace metals adversely affect islet cell functions:Essential trace metals at normal levels play a key role in glucose homeostasis, because they are essential cofactors in glucose metabolic pathways, pancreatic β-cell function and the insulin signaling cascade [6-9]. These essential metals enhance insulin action through activating insulin receptor sites, serving as cofactors or components for enzyme systems involved in glucose metabolism, increase insulin sensitivity [7-9]. However, the proper glucose metabolic functions of the essential metals depend on their normal levels in pancreatic islet. Imbalanced levels (either deficiency or overexposure) of essential metals will adversely affect pancreatic islet cells and cause development of diabetes. For example, Zn at normal levels plays a key role in maintaining the pancreatic islet cell function in the synthesis, storage, and secretion of insulin [7]. Zn deficiency, however, adversely affects the ability of islet cells to produce and secrete insulin [35,36]. Zn at high levels is actually toxic to the islet beta cells because of enhanced oxidative damage [37,38]. Cu deficiency could result in glucose intolerance, decreased insulin response and increase glucose response [9], and might lead to the distortion of mitochondria in pancreatic acinar cells [39]. Se at normal level regulates specific beta cell target genes, promotes improvement in islet function and is a key component of several functional selenoproteins that protect tissues and membranes from oxidative stress [7,9]. Excess Se level has a potential diabetogenic effect possibly by impairing insulin responsiveness; increasing rates of glycolysis; stimulating the release of glucagon and, thus, promoting hyperglycemia or inducing over expression of antioxidant selenoproteins resulting in insulin resistance and obesity [40- 42].
Mg plays a key role in regulating insulin action and insulinmediated glucose uptake. Mg deficiency results in a decrease in insulin mediated glucose uptake [43,44]. Dietary and supplemental Mg has been shown to reduce the risk of T2D [45]. Cr plays an important role in the metabolism of carbohydrates and lipids leading to normalization of the synthesis and secretion of insulin and the optimal glucose uptake by cells [7,46]. Mn is required for normal insulin synthesis and secretion [7]. Altered Mn metabolism was associated with impaired glucose utilization [47]. Elevated body levels of Fe oxidize various biomolecules such as nucleic acids, proteins and lipids which may contribute to T2D development by decreasing insulin secretion from pancreatic beta cells with concomitant increase of insulin resistance [48-50]. Higher Ca concentration impairs carbohydrate and lipid metabolism, while imbalanced Ca levels can have adverse effects on β-cells secretion function and affect normal insulin release [9]. V affects glucose transport, glycolysis, and glucose oxidation and glycogen synthesis [51-53]. Co could cause an increased expression of glucose transporter 1 and inhibition of gluconeogenesis [54]. Thus, while it is indisputable that essential metals at normal levels play an important role in glucose metabolism, imbalanced levels of trace metals, however, could have severe adverse effects on pancreatic islets [6-9,55].
Essential trace metals at normal levels exhibit an antagonistic effect from toxic metal exposures and thus reduce T2D risk induced by toxic metals:Toxic metal-induced oxidative stress causes islet β-cell destruction or dysfunction and increase T2D risk, while essential trace metals with their antioxidant properties at normal levels have the ability to counteract the oxidative stress induced by toxic metals, and thus modulate the toxicity of toxic metals and protect the pancreatic islet β-cells from toxic metal-induced damages. The antagonistic effect existing between essential trace metals and toxic metals plays an important role in maintaining insulin homeostasis and reducing the risk of T2D.Cu together with Zn, for example, is essential for balanced oxidant-antioxidant mechanisms, and Cu and Zn imbalances can increase susceptibility to toxic metalinduced oxidative damage to islet β-cells and thereby lead to the pathogenesis of diabetes [7-10]. Cr is a component or activator of some enzymes, mostly antioxidants. Se is a cofactor of the antioxidant enzyme glutathione peroxidase that enables to reduce the Cd/Pb-induced oxidative stress [56-58].
Toxic metals compete with essential metals for various physiological function and affect T2D risk:Toxic metals compete with essential metals for absorption and excretion; transport of metals in the body; binding to target proteins; metabolism and sequestration of toxic metals [59-61]. Part of Pb toxicity, for example, comes from its ability to mimic other essential metals (such asCa, Fe, and Zn), as it binds to and interacts with many of the same enzymes as these essential metals and, thus, interferes with the enzyme’s ability to catalyze its normal reactions [12]. Cd and Pb have similar chemical and physical properties to Zn, and compete for the binding sites of metal absorptive and enzymatic proteins. Therefore, in case of Zn deficiency and increased exposure to these toxic metals, the body will use Cd and Pb instead of Zn [62]. Cd also competes with Fe for access to intestinal metal uptake transporters [63]. Deficiency of Fe can lead to greater absorption and toxicity of Cd and Pb [64,65]. Se at low concentration can decrease as toxicity via excretion of As-Se compounds, but excessive Se can enhance As toxicity [66]. Ca and Mg also compete with Pb or Cd for intestinal absorption to reduce the toxic metal burden and prevent toxic metal induced tissue damage by competitive binding to active sites of the enzymes [67,68].
Heavy metals increase the risk of diabetes through endocrine disruption: Toxic metals (As, Cd, Pb, Hg) and some of the essential metals (Co. Cu, Cr, Ni, Se) are metalloestrogens and may increase the risk of diabetes through endocrine disruption [69,70]. For example, as was shown to mimic the action of insulin by phosphorylation of PKB/Akt-mediated GLUT4 expression in vitro [6]. Se sustains improvement of glucose homeostasis by exerting insulin like actions in diabetic rats [71]. Cu also possesses an insulin-like activity and promotes lipogenesis [9]. Cr enhances the insulin receptor activity on target tissues [46]. V acts primarily as an insulin mimetic agent affecting glucose transport and glucose oxidation [9].
Heavy metals affect diabetes risk through body weight changes: Low-level Pb exposure during development resulted in later life obesity in adult mice [72]. Pb intake during development caused higher food intake, higher body weight and body fat, and higher insulin response [73]. A study reported that Hg, Mn and Co affect lipid metabolism in the adipose tissue and Hg may accelerate the development of obesity-related diseases in mice [74]. Human studies also found that toxic metals could contribute to weight changes and associated with obesity. A U.S. NHANES study found that Ba and Tl were positively associated while Cd, Co and Pb negatively associated with BMI and waist circumference [75]. U.S. adults who had a higher BMI had lower levels of Hg in their blood [76]. Cd levels in adults were found to be negatively associated with being overweight [77]. Overweight/obese women were found to have a high prevalence of Ni allergy and a low-Ni diet could help loss weight [78].
Epidemiological Evidence of Metal Exposures and T2D Risk
Consistent with findings from experimental studies, epidemiologic studies have provided provocative, albeit inconsistent, evidence supporting the hypothesis that heavy metal exposures increase the risk of T2D as briefly summarized below.
Heavy metal exposures and T2D risk
Previous epidemiological studies have reported statistically significant associations between T2D and exposure to As [79-102], Cd [91,103-105], Hg and Pb [91,105-107], while other studies found no significant association between these toxic metals and T2D risk [77,80,104,108,107-126]. Studies also reported a significant association between imbalances in essential metals and risk of T2D. Specifically, imbalanced levels of Zn [80,91,107,110,117,127-131], Cu [80-117], Mn [107,123,128,129,132,133], Cr [107,128,129], Co [107], Mg [127,134], Mo [80], Ni [80,123,128,133,135-137], W [80,108], and V [129] were associated with an increased risk of T2D. Other studies, however, failed to establish a significant association between these essential metals and T2D risk [80,91,105,107,108,116-118,123,127,129,133-135,138-143].
Major gaps in current epidemiologic studies linking heavy metals to T2D risk
Prior epidemiologic studies have some major limitations in studying the relationship between heavy metal exposures and T2D that could be used to explain the observed inconsistent findings linking heavy metals to T2D as summarized below
Most previous studies were based on cross-sectional designs: For example, among the heavy metals associated with the risk of T2D, As has received earliest and special attention. Out of 34 studies of As exposure and T2D risk, 23 were crosssectional studies [57,79-91,97-99,109-111,116,124,125], 3 case-control studies used blood samples collected after diagnosis [92,112,115]; 3 were retrospective studies, 1 a nested case-control study, and 4 were prospective studies of which 3 studies only measured drinking water As levels [93- 96,100-102,113]. Out of 14 studies of Zn exposure and T2D risk, 13 studies were either cross-sectional or case-control studies using blood samples obtained after T2D diagnosis [80,107,110,115,116,122,126-128,130,132,137,138]. Most of the studies linking other heavy metals to T2D risk were also cross-sectional. It is well known that toxic metals could cause renal tubular dysfunction in patients with established T2D, and that dysfunctional kidneys lose metals through increasing renal excretion that results in their concomitant decrease in the blood [144]. Thus, findings from cross-sectional studies may actually reflect disease consequences, rather than disease causes. A recent large cross-sectional study from U.S. NHANES data reported an increased risk of diabetes associated with metal exposures and concluded that prospective studies are urgently needed to further evaluate metals as risk factors for diabetes [108].
Most previous studies focused on individual metals, rather than the joint effects of multiple metals and ignored possible antidiabetic effects of essential metals in reducing toxic metal toxicity: Despite experimental studies which have shown that heavy metal exposures may increase T2D risk and that essential metals at normal levels could counteract the toxicity from toxic metal exposures on T2D risk, few human studies have directly and comprehensively investigated the effects of multiple metal exposures and the alleged antagonistic effect between essential and toxic metals on T2D risk. Nevertheless, essential trace metals are recommended by some as potential beneficial supplements for the prevention of T2D [22,145-147]. But the fact is that no epidemiologic study has actually investigated the antagonistic effect of essential metals in reducing toxic metal effects nor the optimal levels of essential metals to mitigate the toxic metal effect. Thus, it is considered by some to be immature at this stage to recommend mineral supplementation as a means of prevention of T2D, and additional and methodologically comprehensive prospective follow-up studies are needed to further determine the significance and the optimal levels of the anti-diabetogenic effects of essential metals [7,8,18,45,108,143,148-151]. Establishing optimal body levels of essential metals that reduce the adverse effect of toxic metal exposure could lead to simple, safe, readily available, acceptable and highly affordable nutrition intervention for the prevention of T2D that will have both clinical and public health significance worldwide.
Most previous studies have relied on self-reported T2D: Studies have shown that the undiagnosed T2D rate is high, as 28% of all T2D cases are undiagnosed even in the US [2]. The prevalence of prediabetes, which is associated with an increased risk of T2D, is also high, reaching 37% in U.S. adults [152]. Epidemiologic studies relying on self-reported T2D status and not considering undiagnosed diabetes and prediabetes in their selection of study subjects could cause serious misclassification of disease status in epidemiologic studies, leading to attenuated estimates of the association between metal exposures and T2D risk. Small sample size few epidemiologic studies conducted to date have had the power to study effect modification between essential trace metals and toxic metals in reducing T2D risk.
Suggestions for Future Studies
Due to the inconclusive nature of the reported association and the widespread exposure to heavy metals, there exists an urgent need for large prospective cohort studies to investigate the alleged association. In addressing the major gaps in the current literature, we suggest that future prospective studies or nested case-control studies should:
1. Simultaneously evaluate the role of multiple heavy metal exposures on T2D risk;
2. Assess the antagonistic effect of essential metals in reducing toxic metal effect on T2D;
3. Determine the optimal body levels of essential metals that could mitigate the risk of T2D from toxic metals;
4. Nested case-control study should select both cases and the controls based on physical examinations and clinical biochemistry tests both at baseline and during follow-up.This allows the studies to 1) avoid recruiting cases relying on self-report; 2) identify all incident T2D cases from the cohort; and 3) avoid selecting controls with undiagnosed diabetes and prediabetes that would attenuate associations of metal exposures with T2D.
In summary, there is a general consensus that large and highquality prospective studies of well-characterized populations are urgently needed to further investigate heavy metal exposures as risk factors for T2D, an association that is biologically plausible.
References
- WHO (World Health Organization) (2016) Global report on diabetes.
- USCDC (Centers for Disease Control and Prevention) (2014) National diabetes statistics report: estimates of diabetes and its burden in the United States, 2014. US Department of Health and Human Services, Atlanta, Georgia.
- Narayan KM, Boyle JP, Thompson TJ, Sorensen SW, Williamson DF (2003) Lifetime risk for diabetes mellitus in the United States. JAMA 290(14): 1884-1890.
- Xu Y, Wang L, He J, Bi Y, Li M, et al. (2013) Prevalence and control of diabetes in Chinese adults. JAMA 310(9): 948-959.
- Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ (2012) Heavy metal toxicity and the environment. EXS 101: 133-164.
- Chen YW, Yang CY, Huang CF, Hung DZ, Leung YM, et al. (2009) Heavy metals, islet function and diabetes development. Islets 1(3): 169-176.
- Khan AR, Awan FR (2014) Metals in the pathogenesis of type 2 diabetes. J Diabetes Metab Disord 13(1): 16.
- Kaur B, Henry J (2014) Micronutrient status in type 2 diabetes: a review. Adv Food Nutr Res 71: 55-100.
- Siddiqui K, Bawazeer N, Joy SS (2014) Variation in macro and trace elements in progression of type 2 diabetes. The Scientific World Journal 2014: 461591.
- Edwards J, Ackerman C (2016) A Review of diabetes mellitus and exposure to the environmental toxicant cadmium with an emphasis on likely mechanisms of action. Curr Diabetes Rev 12(3): 252-258.
- Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ (2012) Heavy metal toxicity and the environment. EXS 101: 133-164.
- Sharma B, Singh S, Siddiqi NJ (2014) Biomedical implications of heavy metals induced imbalances in redox systems. Biomed Res Int 2014: 640754.
- Lynn S, Gurr JR, Lai HT, Jan KY (2000) NADH oxidase activation is involved in arsenite-induced oxidative DNA damage in human vascular smooth muscle cells. Circ Res 86(5): 514-519.
- Wu MM, Chiou HY, Wang TW, Hsueh YM, Wang IH, et al. (2001) Association of blood arsenic levels with increased reactive oxidants and decreased antioxidant capacity in a human population of northeastern Taiwan. Environ Health Perspect 109(10): 1011-1017.
- Kurata Y, Katsuta O, Doi T, Kawasuso T, Hiratsuka H, et al. (2003) Chronic cadmium treatment induces islet B cell injury in ovariectomized cynomolgus monkeys. Jpn J Vet Res 50(4): 175-183.
- Demir H, Kanter M, Coskun O, Uz YH, Koc A, et al. (2006) Effect of black cumin (Nigella sativa) on heart rate, some hematological values, and pancreatic beta-cell damage in cadmium-treated rats. Biol Trace Elem Res 110(2): 151-162.
- Liu J, Qu W, Kadiiska MB (2009) Role of oxidative stress in cadmium toxicity and carcinogenesis. Toxicol Appl Pharmacol 238(3): 209-214.
- Serdar MA, Bakir F, Hasimi A, Celik T, Akin O, et al. (2009) Trace and toxic element patterns in nonsmoker patients with noninsulindependent diabetes mellitus, impaired glucose tolerance, and fasting glucose. Int J Diabetes Dev Ctries 29(1): 35-40.
- Siddiqui K, Bawazeer N, Joy SS (2014) Variation in macro and trace elements in progression of type 2 diabetes. The Scientific World Journal 2014: 9.
- Gonzalez Villalva A, Colin Barenque L, Bizarro Nevares P, Rojas Lemus M, Rodriguez Lara V, et al. (2016) Pollution by metals: Is there a relationship in glycemic control? Environ Toxicol Pharmacol 46: 337- 343.
- Bai Y, Yang A, Pu H, Dai M, Cheng N, et al. (2016) Cohort profile: the china metal-exposed workers cohort study (jinchang cohort). Int J Epidemiol 46(4): 1095e-1096e.
- Prasanthi RP, Devi CB, Basha DC, Reddy NS, Reddy GR (2010) Calcium and zinc supplementation protects lead (Pb)-induced perturbations in antioxidant enzymes and lipid peroxidation in developing mouse brain. Int J Dev Neurosci 28(2): 161-167.
- Farmand F, Ehdaie A, Roberts CK, Sindhu RK (2005) Lead-induced dysregulation of superoxide dismutases, catalase, glutathione peroxidase, and guanylate cyclase. Environ Res 98(1): 33-39.
- Kadota I, Kurita M (1955) Hyperglycemia and islet cell damage caused by nickelous chloride. Metabolism 4(4): 337-342.
- Cartana J, Arola L (1992) Nickel-induced hyperglycaemia: the role of insulin and glucagon. Toxicology 71(1-2): 181-192.
- Bwititi PT, Ashorobi RB (1998) Effects of chronic oral nickel chloride administration on glycaemia and renal function in normal and diabetic rats. Afr J Health Sci 5(3-4): 198-201.
- Gupta S, Ahmad N, Husain MM, Srivastava RC (2000) Involvement of nitric oxide in nickel-induced hyperglycemia in rats. Nitric oxide 4(2): 129-138.
- Tikare SN, Das Gupta A, Dhundasi SA, Das KK (2008) Effect of antioxidants L-ascorbic acid and alpha-tocopherol supplementation in nickel exposed hyperglycemic rats. J Basic Clin Physiol Pharmacol 19(2): 89-101.
- Valko M, Morris H, Cronin MT (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12(10): 1161-1208.
- Beyersmann D, Hartwig A (2008) Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms. Arch Toxicol 82(8): 493-512.
- Kaneto H, Katakami N, Kawamori D, Miyatsuka T, Sakamoto K, et al. (2007) Involvement of oxidative stress in the pathogenesis of diabetes. Antioxid Redox Signal 9(3): 355-366.
- Kajimoto Y, Matsuoka T, Kaneto H, Watada H, Fujitani Y, et al. (1999) Induction of glycation suppresses glucokinase gene expression in HIT-T15 cells. Diabetologia 42(12): 1417-1424.
- Kaneto H, Xu G, Song KH, Suzuma K, Bonner Weir S, et al. (2001) Activation of the hexosamine pathway leads to deterioration of pancreatic beta-cell function through the induction of oxidative stress. J Biol Chem 276(33): 31099-31104.
- Han JC, Park SY, Hah BG, Choi GH, Kim YK, et al. (2003) Cadmium induces impaired glucose tolerance in rat by down-regulating GLUT4 expression in adipocytes. Arch Biochem Biophys 413(2): 213-220.
- Rungby J (2010) Zinc, zinc transporters and diabetes. Diabetologia 53(8): 1549-1551.
- Brender JR, Hartman K, Nanga RP, Popovych N, de la Salud Bea R, et al. (2010) Role of zinc in human islet amyloid polypeptide aggregation. Journal of the American Chemical Society 132(26): 8973-8983.
- Lemaire K, Chimienti F, Schuit F (2012) Zinc transporters and their role in the pancreatic beta-cell. J Diabetes Investig 3(3): 202-211.
- Wijesekara N, Chimienti F, Wheeler MB (2009) Zinc, a regulator of islet function and glucose homeostasis. Diabetes Obes Metab 11 Suppl 4: 202-14.
- Quilliot D, Dousset B, Guerci B, Dubois F, Drouin P, et al. (2001) Evidence that diabetes mellitus favors impaired metabolism of zinc, copper, and selenium in chronic pancreatitis. Pancreas 22(3): 299-306.
- Furnsinn C, Englisch R, Ebner K, Nowotny P, Vogl C, et al. (1996) Insulin-like vs. non-insulin-like stimulation of glucose metabolism by vanadium, tungsten, and selenium compounds in rat muscle. Life Sci 59(23): 1989-2000.
- Satyanarayana S, Sekhar JR, Kumar KE, Shannika LB, Rajanna B, et al. (2006) Influence of selenium (antioxidant) on gliclazide induced hypoglycaemia/anti hyperglycaemia in normal/alloxan-induced diabetic rats. Mol Cell Biochem 283(1-2): 123-127.
- Vinceti M, Grioni S, Alber D, Consonni D, Malagoli C, et al. (2015) Toenail selenium and risk of type 2 diabetes: the ORDET cohort study. Journal of trace elements in medicine and biology: organ of the Society for Minerals and Trace Elements (GMS) 29: 145-150.
- Lopez Ridaura R, Willett WC, Rimm EB, Liu S, Stampfer MJ, et al. (2004) Magnesium intake and risk of type 2 diabetes in men and women. Diabetes care 27(1): 134-140.
- Afridi HI, Kazi TG, Kazi N, Jamali MK, Arain MB, et al. (2008) Potassium, calcium, magnesium, and sodium levels in biological samples of hypertensive and nonhypertensive diabetes mellitus patients. Biol Trace Elem Res 124(3): 206-224.
- Fang X, Han H, Li M, Liang C, Fan Z, et al. (2016) Dose-Response Relationship between Dietary Magnesium Intake and Risk of Type 2 Diabetes Mellitus: A Systematic Review and Meta-Regression Analysis of Prospective Cohort Studies. Nutrients 8(11).
- Qiao W, Peng Z, Wang Z, Wei J, Zhou A (2009) Chromium improves glucose uptake and metabolism through upregulating the mRNA levels of IR, GLUT4, GS, and UCP3 in skeletal muscle cells. Biol Trace Elem Res 131(2): 133-142.
- Everson GJ, Shrader RE (1968) Abnormal glucose tolerance in manganese-deficient guinea pigs. J Nutr 94(1): 89-94.
- Jiang R, Manson JE, Meigs JB, Ma J, Rifai N, et al. (2004) Body iron stores in relation to risk of type 2 diabetes in apparently healthy women. JAMA 291(6): 711-717.
- Lee DH, Liu DY, Jacobs DR, Shin HR, Song K, et al. (2006) Common presence of non-transferrin-bound iron among patients with type 2 diabetes. Diabetes care 29(5): 1090-1095.
- Jehn M, Clark JM, Guallar E (2004) Serum ferritin and risk of the metabolic syndrome in U.S. adults. Diabetes care 27(10): 2422-2428.
- Cam MC, Brownsey RW, McNeill JH (2000) Mechanisms of vanadium action: insulin-mimetic or insulin-enhancing agent? Can J Physiol Pharmacol 78(10): 829-847.
- Poucheret P, Verma S, Grynpas MD, McNeill JH (1998) Vanadium and diabetes. Mol Cell Biochem 188(1-2): 73-80.
- Orvig C, Thompson KH, Battell M, McNeill JH (1995) Vanadium compounds as insulin mimics. Met Ions Biol Syst 31: 575-594.
- Saker F, Ybarra J, Leahy P, Hanson RW, Kalhan SC, et al. (1998) Glycemialowering effect of cobalt chloride in the diabetic rat: role of decreased gluconeogenesis. Am J Physiol 274(6 Pt 1): E984-E991.
- Peraza MA, Ayala Fierro F, Barber DS, Casarez E, Rael LT (1998) Effects of micronutrients on metal toxicity. Environ Health Perspect 106 Suppl 1: 203-216.
- Luchese C, Brandao R, de Oliveira R, Nogueira CW, Santos FW (2007) Efficacy of diphenyl diselenide against cerebral and pulmonary damage induced by cadmium in mice. Toxicol Lett 173(3): 181-190.
- Liu MC, Xu Y, Chen YM, Li J, Zhao F, et al. (2013) The effect of sodium selenite on lead induced cognitive dysfunction. Neurotoxicology 36: 82-88.
- Brenneisen P, Steinbrenner H, Sies H (2005) Selenium, oxidative stress, and health aspects. Mol Aspects Med 26(4-5): 256-267.
- Ahamed M, Siddiqui MK (2007) Environmental lead toxicity and nutritional factors. Clinical nutrition 26(4): 400-408.
- Vesey DA (2010) Transport pathways for cadmium in the intestine and kidney proximal tubule: focus on the interaction with essential metals. Toxicol Lett 198(1): 13-19.
- Flora SJ (2009) Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure. Oxid Med Cell Longev 2(4): 191-206.
- Duruibe J, Ogwuegbu M, Egwurugwu J (2007) Heavy metal pollution and human biotoxic effects. International Journal of Physical Sciences 2(5): 112-118.
- Ryu DY, Lee SJ, Park DW, Choi BS, Klaassen CD, et al. (2004) Dietary iron regulates intestinal cadmium absorption through iron transporters in rats. Toxicol Lett 152(1): 19-25.
- Reeves PG, Chaney RL (2004) Marginal nutritional status of zinc, iron, and calcium increases cadmium retention in the duodenum and other organs of rats fed rice-based diets. Environ Res 96(3): 311-322.
- Hammad TA, Sexton M, Langenberg P (1996) Relationship between blood lead and dietary iron intake in preschool children. A crosssectional study. Ann Epidemiol 6(1): 30-33.
- Sun HJ, Rathinasabapathi B, Wu B, Luo J, Pu LP, et al. (2014) Arsenic and selenium toxicity and their interactive effects in humans. Environ Int 69: 148-158.
- Basha DC, Rani MU, Devi CB, Kumar MR, Reddy GR (2012) Perinatal lead exposure alters postnatal cholinergic and aminergic system in rat brain: reversal effect of calcium co-administration. Int J Dev Neurosci 30(4): 343-350.
- Djukic Cosic D, Ninkovic M, Malicevic Z, Matovic V, Soldatovic D (2007) Effect of magnesium pretreatment on reduced glutathione levels in tissues of mice exposed to acute and subacute cadmium intoxication: a time course study. Magnes Res 20(3): 177-186.
- Choe SY, Kim SJ, Kim HG, Lee JH, Choi Y, et al. (2003) Evaluation of estrogenicity of major heavy metals. Sci Total Environ 312(1-3): 15-21.
- Henson MC, Chedrese PJ (2004) Endocrine disruption by cadmium, a common environmental toxicant with paradoxical effects on reproduction. Exp Biol Med (Maywood) 229(5): 383-392.
- Roden M, Prskavec M, Furnsinn C, Elmadfa I, Konig J, et al. (1995) Metabolic effect of sodium selenite: insulin-like inhibition of glucagonstimulated glycogenolysis in the isolated perfused rat liver. Hepatology 22(1): 169-174.
- Leasure JL, Giddabasappa A, Chaney S, Johnson JE, Pothakos K, et al. (2008) Low-level human equivalent gestational lead exposure produces sex-specific motor and coordination abnormalities and lateonset obesity in year-old mice. Environmental health perspectives 116(3): 355-361.
- Faulk C, Barks A, Sanchez BN, Zhang Z, Anderson OS, et al. (2014) Perinatal lead (Pb) exposure results in sex-specific effects on food intake, fat, weight, and insulin response across the murine life-course. PloS one 9(8): e104273.
- Kawakami T, Hanao N, Nishiyama K, Kadota Y, Inoue M, et al. (2012) Differential effects of cobalt and mercury on lipid metabolism in the white adipose tissue of high-fat diet-induced obesity mice. Toxicol Appl Pharmacol 258(1): 32-42.
- Padilla MA, Elobeid M, Ruden DM, Allison DB (2010) An examination of the association of selected toxic metals with total and central obesity indices: NHANES 99-02. Int J Environ Res Public Health 7(9): 3332- 3347.
- Rothenberg SE, Korrick SA, Fayad R (2015) The influence of obesity on blood mercury levels for U.S. non-pregnant adults and children: NHANES 2007-2010. Environ Res 138: 173-180.
- Nie X, Wang N, Chen Y, Chen C, Han B, et al. (2016) Blood cadmium in Chinese adults and its relationships with diabetes and obesity. Environ Sci Pollut Res Int 23(18): 18714-18723.
- Lusi EA, Di Ciommo VM, Patrissi T, Guarascio P (2015) High prevalence of nickel allergy in an overweight female population: a pilot observational analysis. PLoS One 10(3): e0123265.
- Del Razo LM, Garcia Vargas GG, Valenzuela OL, Castellanos EH, Sanchez Pena LC, et al. (2011) Exposure to arsenic in drinking water is associated with increased prevalence of diabetes: a cross-sectional study in the Zimapan and Lagunera regions in Mexico. Environmental health 10: 73.
- Feng W, Cui X, Liu B, Liu C, Xiao Y, et al. (2015) Association of urinary metal profiles with altered glucose levels and diabetes risk: a population-based study in China. PLoS One 10(4): e0123742.
- Feseke SK, St Laurent J, Anassour Sidi E, Ayotte P, Bouchard M, et al. (2015) Arsenic exposure and type 2 diabetes: results from the 2007- 2009 Canadian Health Measures Survey. Health Promot Chronic Dis Prev Can 35(4): 63-72.
- Gribble MO, Howard BV, Umans JG, Shara NM, Francesconi KA, et al. (2012) Arsenic exposure, diabetes prevalence, and diabetes control in the Strong Heart Study. Am J Epidemiol 176(10): 865-874.
- Kim Y, Lee BK (2011) Association between urinary arsenic and diabetes mellitus in the Korean general population according to KNHANES 2008. Sci Total Environ 409(19): 4054-4062.
- Lai MS, Hsueh YM, Chen CJ, Shyu MP, Chen SY, et al. (1994) Ingested inorganic arsenic and prevalence of diabetes mellitus. Am J Epidemiol 139(5): 484-492.
- Mendez MA, Gonzalez Horta C, Sanchez Ramirez B, Ballinas Casarrubias L, Ceron RH, et al. (2016) Chronic exposure to arsenic and markers of cardiometabolic risk: a cross-sectional study in chihuahua, Mexico. Environmental health perspectives. 124(1): 104-111.
- Navas Acien A, Silbergeld EK, Pastor Barriuso R, Guallar E (2009) Rejoinder: Arsenic exposure and prevalence of type 2 diabetes: updated findings from the National Health Nutrition and Examination Survey, 2003-2006. Epidemiology 20(6): 816-820.
- Navas Acien A, Silbergeld EK, Pastor Barriuso R, Guallar E (2008) Arsenic exposure and prevalence of type 2 diabetes in US adults. JAMA 300(7): 814-822.
- Rahman M, Tondel M, Ahmad SA, Axelson O (1998) Diabetes mellitus associated with arsenic exposure in Bangladesh. Am J Epidemiol 148(2): 198-203.
- Rahman M, Tondel M, Chowdhury IA, Axelson O (1999) Relations between exposure to arsenic, skin lesions, and glucosuria. Occup Environ Med 56(4): 277-281.
- Wang SL, Chiou JM, Chen CJ, Tseng CH, Chou WL, et al. (2003) Prevalence of non-insulin-dependent diabetes mellitus and related vascular diseases in southwestern arseniasis-endemic and nonendemic areas in Taiwan. Environ Health Perspect 111(2): 155-159.
- Afridi HI, Kazi TG, Kazi N, Jamali MK, Arain MB, et al. (2008) Evaluation of status of toxic metals in biological samples of diabetes mellitus patients. Diabetes Res Clin Pract 80(2): 280-288.
- Coronado Gonzalez JA, Del Razo LM, Garcia Vargas G, Sanmiguel Salazar F, Escobedo de la Pena J (2007) Inorganic arsenic exposure and type 2 diabetes mellitus in Mexico. Environ Res 104(3): 383-389.
- James KA, Marshall JA, Hokanson JE, Meliker JR, Zerbe GO, et al. (2013) A case-cohort study examining lifetime exposure to inorganic arsenic in drinking water and diabetes mellitus. Environ Res 123: 33-38.
- Tseng CH, Tai TY, Chong CK, Tseng CP, Lai MS, et al. (2000) Long-term arsenic exposure and incidence of non-insulin-dependent diabetes mellitus: a cohort study in arseniasis-hyperendemic villages in Taiwan. Environ Health Perspect 108(9): 847-851.
- Kim NH, Mason CC, Nelson RG, Afton SE, Essader AS, et al. (2013) Arsenic exposure and incidence of type 2 diabetes in Southwestern American Indians. Am J Epidemiol 177(9): 962-969.
- Tsai SM, Wang TN, Ko YC (1999) Mortality for certain diseases in areas with high levels of arsenic in drinking water. Arch Environ Health 54(3): 186-193.
- Currier JM, Ishida MC, Gonzalez Horta C, Sanchez Ramirez B, Ballinas Casarrubias L, et al. (2014) Associations between arsenic species in exfoliated urothelial cells and prevalence of diabetes among residents of Chihuahua, Mexico. Environ Health Perspect 122(10): 1088-1094.
- Jovanovic D, Rasic Milutinovic Z, Paunovic K, Jakovljevic B, Plavsic S, et al. (2013) Low levels of arsenic in drinking water and type 2 diabetes in Middle Banat region, Serbia. Int J Hyg Environ Health 216(1): 50-55.
- Rhee SY, Hwang YC, Woo JT, Chin SO, Chon S, et al. (2013) Arsenic exposure and prevalence of diabetes mellitus in Korean adults. J Korean Med Sci 28(6): 861-868.
- Brauner EV, Nordsborg RB, Andersen ZJ, Tjonneland A, Loft S, et al. (2014) Long-term exposure to low-level arsenic in drinking water and diabetes incidence: a prospective study of the diet, cancer and health cohort. Environmental health perspectives. 122(10): 1059- 1065.
- D’Ippoliti D, Santelli E, De Sario M, Scortichini M, Davoli M, et al. (2015) Arsenic in drinking water and mortality for cancer and chronic diseases in central Italy, 1990-2010. PLoS One 10(9): e0138182.
- Kuo CC, Howard BV, Umans JG, Gribble MO, Best LG, et al. (2015) Arsenic exposure, arsenic metabolism, and incident diabetes in the strong heart study. Diabetes care 38(4): 620-627.
- Schwartz GG, Il’yasova D, Ivanova A (2003) Urinary cadmium, impaired fasting glucose, and diabetes in the NHANES III. Diabetes care 26(2): 468-470.
- Swaddiwudhipong W, Nguntra P, Kaewnate Y, Mahasakpan P, Limpatanachote P, et al. (2015) Human health effects from cadmium exposure: comparison between persons living in cadmiumcontaminated and non-contaminated areas in Northwestern Thailand. Southeast Asian J Trop Med Public Health 46(1): 133-142.
- Afridi HI, Kazi TG, Brabazon D, Naher S, Talpur FN (2013) Comparative metal distribution in scalp hair of Pakistani and Irish referents and diabetes mellitus patients. Clinica chimica acta. international journal of clinical chemistry 415: 207-214.
- He K, Xun P, Liu K, Morris S, Reis J, et al. (2013) Mercury exposure in young adulthood and incidence of diabetes later in life: the CARDIA Trace Element Study. Diabetes care 36(6): 1584-1589.
- Cancarini A, Fostinelli J, Napoli L, Gilberti ME, Apostoli P, et al. (2017) Trace elements and diabetes: Assessment of levels in tears and serum. Exp Eye Res 154: 47-52.
- Menke A, Guallar E, Cowie CC (2016) Metals in urine and diabetes in U.S. adults. Diabetes 65(1): 164-171.
- Chen Y, Ahsan H, Slavkovich V, Peltier GL, Gluskin RT, et al. (2010) No association between arsenic exposure from drinking water and diabetes mellitus: a cross-sectional study in Bangladesh. Environ Health Perspect 118(9): 1299-1305.
- Islam R, Khan I, Hassan SN, McEvoy M, D’Este C, et al. (2012) Association between type 2 diabetes and chronic arsenic exposure in drinking water: a cross sectional study in Bangladesh. Environ Health 11: 38.
- Li X, Li B, Xi S, Zheng Q, Lv X, et al. (2013) Prolonged environmental exposure of arsenic through drinking water on the risk of hypertension and type 2 diabetes. Environ Sci Pollut Res Int 20(11): 8151-8161.
- Makris KC, Christophi CA, Paisi M, Ettinger AS (2012) A preliminary assessment of low level arsenic exposure and diabetes mellitus in Cyprus. BMC public health 12: 334.
- Nabi AH, Rahman MM, Islam LN (2005) Evaluation of biochemical changes in chronic arsenic poisoning among Bangladeshi patients. Int J Environ Res Public Health 2(3-4): 385-393.
- Tollestrup K, Frost FJ, Harter LC, McMillan GP (2003) Mortality among children residing near the American Smelting and Refining Company (ASARCO) copper smelter in Ruston, Washington. Arch Environ Health 58(11): 683-691.
- Barregard L, Bergstrom G, Fagerberg B (2013) Cadmium exposure in relation to insulin production, insulin sensitivity and type 2 diabetes: a cross-sectional and prospective study in women. Environmental research 121: 104-109.
- Hansen AF, Simic A, Asvold BO, Romundstad PR, Midthjell K, et al. (2017) Trace elements in early phase type 2 diabetes mellitus-A population-based study. The HUNT study in Norway. J Trace Elem Med Biol 40: 46-53.
- Liu B, Feng W, Wang J, Li Y, Han X,et al. (2016) Association of urinary metals levels with type 2 diabetes risk in coke oven workers. Environ Pollut 210: 1-8.
- Moon SS (2013) Association of lead, mercury and cadmium with diabetes in the Korean population: the Korea National Health and Nutrition Examination Survey (KNHANES) 2009-2010. Diabet Med 30(4): e143-e148.
- Swaddiwudhipong W, Mahasakpan P, Limpatanachote P, Krintratun S (2010) Correlations of urinary cadmium with hypertension and diabetes in persons living in cadmium-contaminated villages in northwestern Thailand: A population study. Environ Res 110(6): 612-616.
- Swaddiwudhipong W, Limpatanachote P, Nishijo M, Honda R, Mahasakpan P, et al. (2010) Cadmium-exposed population in Mae Sot district, Tak province: 3. Associations between urinary cadmium and renal dysfunction, hypertension, diabetes, and urinary stones. J Med Assoc Thai 93(2): 231-238.
- Borne Y, Fagerberg B, Persson M, Sallsten G, Forsgard N, et al. (2014) Cadmium exposure and incidence of diabetes mellitus--results from the Malmo Diet and Cancer study. PLoS One 9(11): e112277.
- Van Larebeke N, Sioen I, Hond ED, Nelen V, Van de Mieroop E, et al. (2015) Internal exposure to organochlorine pollutants and cadmium and self-reported health status: a prospective study. Int J Hyg Environ Health 218(2): 232-245.
- Forte G, Bocca B, Peruzzu A, Tolu F, Asara Y, et al. (2013) Blood metals concentration in type 1 and type 2 diabetics. Biol Trace Elem Res 156(1-3): 79-90.
- Mozaffarian D, Shi P, Morris JS, Grandjean P, Siscovick DS, et al. (2013) Methylmercury exposure and incident diabetes in U.S. men and women in two prospective cohorts. Diabetes care 36(11): 3578- 3584.
- Huang JW, Cheng YY, Sung TC, Guo HR, Sthiannopkao S (2014) Association between arsenic exposure and diabetes mellitus in Cambodia. Biomed Res Int 2014: 683124.
- Zierold KM, Knobeloch L, Anderson H (2004) Prevalence of chronic diseases in adults exposed to arsenic-contaminated drinking water. Am J Public Health 94(11): 1936-1937.
- Humayun M, Khalid A, Ali A, Ahamad S, Javed A (2011) To Study the levels of serum chromium, copper, Mg and Zn in patients with T2DM. Pakistan Journal of Medical and Health Sciences.
- Chen H, Tan C (2012) Prediction of type-2 diabetes based on several element levels in blood and chemometrics. Biol Trace Elem Res 147(1-3): 67-74.
- Ekmekcioglu C, Prohaska C, Pomazal K, Steffan I, Schernthaner G, et al. (2001) Concentrations of seven trace elements in different hematological matrices in patients with type 2 diabetes as compared to healthy controls. Biol Trace Elem Res 79(3): 205-219.
- Yary T, Virtanen JK, Ruusunen A, Tuomainen TP, Voutilainen S (2016) Serum zinc and risk of type 2 diabetes incidence in men: the kuopio ischaemic heart disease risk factor study. J Trace Elem Med Biol 33: 120-124.
- Al Timimi DJ, Mahmoud HM, Mohammed DA, Ahmed IH (2015) Serum zinc and metabolic health status in siblings of patients with type 2 diabetes mellitus. J Clin Diagn Res 9(12): Bc05-Bc08
- Shan Z, Chen S, Sun T, Luo C, Guo Y, et al. (2016) U-shaped association between plasma manganese levels and type 2 diabetes. Environ Health Perspect 124(12): 1876-1881.
- Kazi TG, Afridi HI, Kazi N, Jamali MK, Arain MB, et al. (2008) Copper, chromium, manganese, iron, nickel, and zinc levels in biological samples of diabetes mellitus patients. Biol Trace Elem Res 122(1): 1-18.
- Kao WH, Folsom AR, Nieto FJ, Mo JP, Watson RL, et al. (1999) Serum and dietary magnesium and the risk for type 2 diabetes mellitus: the Atherosclerosis Risk in Communities Study. Arch Intern Med 159(18): 2151-2159.
- Liu G, Sun L, Pan A, Zhu M, Li Z, et al. (2015) Nickel exposure is associated with the prevalence of type 2 diabetes in Chinese adults. Int J Epidemiol 44(1): 240-248.
- Yang AM, Cheng N, Pu HQ, Liu SM, Li JS, et al. (2015) Metal Exposure and risk of diabetes and prediabetes among chinese occupational workers. Biomed Environ Sci 28(12): 875-883.
- Aguilar MV, Saavedra P, Arrieta FJ, Mateos CJ, Gonzalez MJ, et al. (2007) Plasma mineral content in type-2 diabetic patients and their association with the metabolic syndrome. Ann Nutr Metab 51(5): 402-406.
- Yin Y, Han W, Wang Y, Zhang Y, Wu S, et al. (2015) Identification of risk factors affecting impaired fasting glucose and diabetes in adult patients from Northeast China. Int J Environ Res Public Health 12(10): 12662-12678.
- Zahra h, Mansournia N, Meimand ZM (2016) Serum Zinc levels in patients with type 2 diabetes mellitus compared with the control group. Scholar Rrsearch Library 8(14): 23-26.
- Ma J, Folsom AR, Melnick SL, Eckfeldt JH, Sharrett AR, et al. (1995) Associations of serum and dietary magnesium with cardiovascular disease, hypertension, diabetes, insulin, and carotid arterial wall thickness: the ARIC study. Atherosclerosis Risk in Communities Study. J Clin Epidemiol 48(7): 927-940.
- Hruby A, Meigs JB, O’Donnell CJ, Jacques PF, McKeown NM (2014) Higher magnesium intake reduces risk of impaired glucose and insulin metabolism and progression from prediabetes to diabetes in middle-aged Americans. Diabetes care 37(2): 419-427.
- Oba S, Nanri A, Kurotani K, Goto A, Kato M, et al. (2013) Dietary glycemic index, glycemic load and incidence of type 2 diabetes in Japanese men and women: the Japan Public Health Center-based Prospective Study. Nutr J 12(1): 165.
- Hata A, Doi Y, Ninomiya T, Mukai N, Hirakawa Y, et al. (2013) Magnesium intake decreases Type 2 diabetes risk through the improvement of insulin resistance and inflammation: the Hisayama Study. Diabet Med 30(12): 1487-1494.
- Thayer KA, Heindel JJ, Bucher JR, Gallo MA (2012) Role of environmental chemicals in diabetes and obesity: a National Toxicology Program workshop review. Environ Health Perspect 120(6): 779-789.
- Kosnett MJ (2010) Chelation for heavy metals (arsenic, lead, and mercury): protective or perilous? Clin Pharmacol Ther 88(3): 412- 415.
- Sah S, Vandenberg A, Smits J (2013) Treating chronic arsenic toxicity with high selenium lentil diets. Toxicol Appl Pharmacol 272(1): 256- 262.
- Zhai Q, Narbad A, Chen W (2015) Dietary strategies for the treatment of cadmium and lead toxicity. Nutrients. 7(1): 552-571.
- Kuo CC, Moon K, Thayer KA, Navas Acien A (2013) Environmental chemicals and type 2 diabetes: an updated systematic review of the epidemiologic evidence. Curr Diab Rep 13(6): 831-849.
- Martini LA, Catania AS, Ferreira SR (2010) Role of vitamins and minerals in prevention and management of type 2 diabetes mellitus. Nutr Rev 68(6): 341-354.
- Barbagallo M, Dominguez LJ (2007) Magnesium metabolism in type 2 diabetes mellitus, metabolic syndrome and insulin resistance. Arch Biochem Biophys 458(1): 40-47.
- Song Y, Chou EL, Baecker A, You NC, Song Y, et al. (2016) Endocrinedisrupting chemicals, risk of type 2 diabetes, and diabetes-related metabolic traits: A systematic review and meta-analysis. J Diabetes 8(4): 516-532.
- Rotter I, Kosik Bogacka D, Dolegowska B, Safranow K, Lubkowska A, et al. (2015) Relationship between the concentrations of heavy metals and bioelements in aging men with metabolic syndrome. Int J Environ Res Public Health 12(4): 3944-3961.