Does Zinc Really “Metal” with Diabetes? The Epidemiologic Evidence

Ruz, Manuel; Carrasco, Fernando; Sánchez, A Prieto; Pérez, A.; Rojas, Pamela

doi:10.1007/s11892-016-0803-x

Cited by 18 publications

(8 citation statements)

References 65 publications

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“…In humans, zinc supplementation alleviates markers of oxidative stress (72). Yet, despite all of these insights, including urinary loss of zinc in diabetic patients, and some positive effects of zinc supplementation in zinc-deficient humans, epidemiological studies and systematic reviews of prospective cohort studies are inconclusive as to whether zinc supplementation prevents type 2 diabetes (73–75). The consensus is, however, that more well-designed intervention studies are needed to evaluate this important aspect of public health.…”

Section: Nutritional Approaches To Prevent and Treat Diabetesmentioning

confidence: 99%

Zinc in Pancreatic Islet Biology, Insulin Sensitivity, and Diabetes

Maret

2017

JFN

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About 20 chemical elements are nutritionally essential for humans with defined molecular functions. Several essential and nonessential biometals are either functional nutrients with antidiabetic actions or can be diabetogenic. A key question remains whether changes in the metabolism of biometals and biominerals are a consequence of diabetes or are involved in its etiology. Exploration of the roles of zinc (Zn) in this regard is most revealing because 80 years of scientific discoveries link zinc and diabetes. In pancreatic β- and α-cells, zinc has specific functions in the biochemistry of insulin and glucagon. When zinc ions are secreted during vesicular exocytosis, they have autocrine, paracrine, and endocrine roles. The membrane protein ZnT8 transports zinc ions into the insulin and glucagon granules. ZnT8 has a risk allele that predisposes the majority of humans to developing diabetes. In target tissues, increased availability of zinc enhances the insulin response by inhibiting protein tyrosine phosphatase 1B, which controls the phosphorylation state of the insulin receptor and hence downstream signalling. Inherited diseases of zinc metabolism, environmental exposures that interfere with the control of cellular zinc homeostasis, and nutritional or conditioned zinc deficiency influence the patho-biochemistry of diabetes. Accepting the view that zinc is one of the many factors in multiple gene-environment interactions that cause the functional demise of β-cells generates an immense potential for treating and perhaps preventing diabetes. Personalized nutrition, bioactive food, and pharmaceuticals targeting the control of cellular zinc in precision medicine are among the possible interventions.

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Section: Nutritional Approaches To Prevent and Treat Diabetesmentioning

confidence: 99%

Zinc in Pancreatic Islet Biology, Insulin Sensitivity, and Diabetes

Maret

2017

JFN

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“…Zn has a potential to be utilized for the treatment of type 2 diabetes; however, the epidemiologic evidence suggests that the effect of Zn on type 2 diabetes remains unclear (10). Up to 85% of the whole body Zn content is found in muscle and bones, with 11% in the skin and liver (11).…”

Section: Introductionmentioning

confidence: 99%

Serum Zn/Cu Ratio Is Associated with Renal Function, Glycemic Control, and Metabolic Parameters in Japanese Patients with and without Type 2 Diabetes: A Cross-sectional Study

2016

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BackgroundZinc (Zn) and copper (Cu) may play a pivotal role in the pathogenesis of diabetes and diabetic complications by mediating oxidative stress. Both Zn deficiency and excess of Cu are associated with an increased risk of type 2 diabetes and cardiovascular disease. We aimed to investigate the relationships between serum Zn/Cu ratio and glycemic status, renal function, and metabolic parameters in patients with and without type 2 diabetes.MethodsWe conducted a cross-sectional study on 355 subjects (149 type 2 diabetic and 206 non-diabetic) in whom serum Zn and Cu levels were measured at the same time. Associations between serum Zn/Cu ratio and clinical data were evaluated using multiple regression analysis. We also evaluated associations between serum Zn/Cu ratio and the prevalence of type 2 diabetes and glycemic control by multivariate logistic regression analysis.ResultsSerum Zn/Cu ratio was positively associated with estimated glomerular filtration rate after adjustment for body mass index (BMI) (β = 0.137, p = 0.014). Plasma B-type natriuretic peptide levels were negatively associated with serum Zn/Cu ratio after adjustment for age, sex, and BMI (β = −0.258, p = 0.032). In patients with type 2 diabetes, serum Zn/Cu ratio was negatively associated with plasma HbA1c levels after adjustment for age, sex, and BMI (β = −0.239, p = 0.003). In addition, multivariate logistic regression analysis revealed that the highest quartile of serum Zn/Cu ratio was associated with a reduced risk of poor (HbA1c ≥ 7%) glycemic control (odds ratio = 0.382; 95% confidence interval, 0.165–0.884; p = 0.025) in patients with type 2 diabetes.ConclusionSerum Zn/Cu ratio was favorably associated with renal function in all subjects and glycemic control in patients with type 2 diabetes. The Zn/Cu ratio, in addition to the individual serum levels of trace elements, is important for metabolism in humans.

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“…Capdor et al [57] found a modest reduction in glucose concentration and tendency for a decrease in HbA1c following zinc supplementation and suggested that zinc may contribute to the management of hyperglycemia in individuals with chronic metabolic disease. Ruz et al [58] remarked that studies available to date on zinc supplementation in type 2 Dm suggest that zinc supplementation is only effective in patients with initially reduced zinc concentrations.…”

Section: Main Textmentioning

confidence: 99%

“…Zinc administration increased glucose disposal entirely due to noninsulin-mediated glucose uptake without any systematic effect on insulin secretion and sensitivity [65]. Ruz et al [58] recommended to further determine the role of zinc in type 2 Dm and therapeutic effectiveness of supplementation by long-term studies under observation of factors such as stage of disease, comorbidities, that is, also NAFLD, duration and type of medication (zinc preparation), and, finally, also examining the genetic variations in SLC30A8 as well due to the heterogeneity and complexity with multiple influences on the disease (Figure 1).…”

Section: Main Textmentioning

confidence: 99%

Non-Alcoholic Fatty Liver Disease, Diabetes Mellitus, and Zinc/ Zinc Transporters: Is there a Connection?

Grüngreiff¹

2018

Liver Research and Clinical Management

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Immune response and metabolic regulation are closely connected with each other in such a way that dysfunction could lead to a variety of metabolic diseases such as obesity, diabetes mellitus (Dm), lipid metabolism disorders, and fatty liver disorders. Combined with uncritical "sugar-based" overeating and malnutrition, these multisystem metabolic diseases expand into a global epidemic. There are correlations between a fatty liver disease and diabetic metabolism state. A fatty liver leads to insulin resistance and thus to the development of a type 2 Dm; insulin resistance in turn augments the fatty liver. Zinc is a trace element of fundamental importance for a variety of biological processes. The liver is the main organ of the zinc metabolism. Metallothionein and zinc transporters are the key regulators of cellular zinc homeostasis. Molecular studies support the assumption of a correlation between zinc and Dm. Zinc is essential for the synthesis, secretion, and storage of insulin. ZnT8 is a significant autoantigen for type 1 Dm. Genetic polymorphisms in the ZnT8 gene are associated with an increased risk of developing type 2 Dm. Cellular zinc restriction induces the release of stress, particularly in the endoplasmic reticulum (ER). ER stress alone or coupled with cellular stress, as well as chronic inflammation, are central to the development of insulin resistance and type 2 Dm. The present insights into the context of a non-alcoholic fatty liver disease (NAFLD) and a type 2 Dm indicate that zinc and zinc transporters at the cellular level in various forms and in interactions with other mediators both in the regulation of physiological processes and in the formation of pathological processes, such as the cellular and ER stress, as well as chronic inflammation, and the development of metabolic disorders are involved.

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Does Zinc Really “Metal” with Diabetes? The Epidemiologic Evidence

Cited by 18 publications

References 65 publications

Zinc in Pancreatic Islet Biology, Insulin Sensitivity, and Diabetes

Zinc in Pancreatic Islet Biology, Insulin Sensitivity, and Diabetes

Serum Zn/Cu Ratio Is Associated with Renal Function, Glycemic Control, and Metabolic Parameters in Japanese Patients with and without Type 2 Diabetes: A Cross-sectional Study

Non-Alcoholic Fatty Liver Disease, Diabetes Mellitus, and Zinc/ Zinc Transporters: Is there a Connection?

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