Zinc and Other Metals Deficiencies and Risk of Type 1 Diabetes: An Ecological Study in the High Risk Sardinia Island

Valera, Paolo; Zavattari, Patrizia; Sanna, Alessandro; Pretti, S.; Marcello, A.; Mannu, Carla; Targhetta, Clara; Bruno, Graziella; Songini, Marco

doi:10.1371/journal.pone.0141262

Cited by 27 publications

(19 citation statements)

References 41 publications

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“…In addition, environmental factors that affect zinc levels in soil and water may be important in determining disease risk. Ecological studies have shown negative associations between zinc levels in soil and onset of autoimmune diseases, specifically Type 1 DM [49] and multiple sclerosis [50], suggesting that natural zinc bioavailability in different locations can influence risk of developing diseases. …”

Section: Discussionmentioning

confidence: 99%

Zinc Status and Risk of Cardiovascular Diseases and Type 2 Diabetes Mellitus—A Systematic Review of Prospective Cohort Studies

2016

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Zinc is an essential trace element with proposed therapeutic effects in Type 2 diabetes mellitus (DM), however, the associations between zinc status and the prospective risks of cardiovascular diseases (CVD) and Type 2 DM have not been evaluated. The current systematic review aims to determine the relationships between zinc intake or plasma/serum zinc levels and prospective incidence of CVD and Type 2 DM. Fourteen papers describing prospective cohort studies were included, reporting either CVD (n = 91,708) and/or Type 2 DM (n = 334,387) outcomes. Primary analyses from four out of five studies reported no association between zinc intake and CVD events, when adjusted for multiple variables. Higher serum zinc level was associated with lower risk of CVD in three out of five studies; pronounced effects were observed in vulnerable populations, specifically those with Type 2 DM and patients referred to coronary angiography. The limited evidence available suggests no association between zinc status and Type 2 DM risk. Further investigations into the mechanisms of zinc’s action on the pathogenesis of chronic diseases and additional evidence from observational studies are required to establish a recommendation for dietary zinc in relation to the prevention of CVD and Type 2 DM.

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Section: Discussionmentioning

confidence: 99%

Zinc Status and Risk of Cardiovascular Diseases and Type 2 Diabetes Mellitus—A Systematic Review of Prospective Cohort Studies

2016

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“…This is important in relation to environmental factors such as zinc in drinking water and soils. Although T1DM is clearly related to genetic factors such as HLA-DR3-DQ2 and HLA-DR4-DQ8 [ 318 ], the risk of onset of T1DM is associated with low levels of zinc in drinking water and soils [ 233 , 334 ]. Moreover, zinc deficiency triggers the IL-6-induced phosphorylation of STAT3 [ 145 ], thereby pathologically enhancing B cell differentiation into antibody-producing plasma cells and autoantibody production.…”

Section: Zinc Deficiency In the Context Of Diseasementioning

confidence: 99%

Zinc as a Gatekeeper of Immune Function

2017

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After the discovery of zinc deficiency in the 1960s, it soon became clear that zinc is essential for the function of the immune system. Zinc ions are involved in regulating intracellular signaling pathways in innate and adaptive immune cells. Zinc homeostasis is largely controlled via the expression and action of zinc “importers” (ZIP 1–14), zinc “exporters” (ZnT 1–10), and zinc-binding proteins. Anti-inflammatory and anti-oxidant properties of zinc have long been documented, however, underlying mechanisms are still not entirely clear. Here, we report molecular mechanisms underlying the development of a pro-inflammatory phenotype during zinc deficiency. Furthermore, we describe links between altered zinc homeostasis and disease development. Consequently, the benefits of zinc supplementation for a malfunctioning immune system become clear. This article will focus on underlying mechanisms responsible for the regulation of cellular signaling by alterations in zinc homeostasis. Effects of fast zinc flux, intermediate “zinc waves”, and late homeostatic zinc signals will be discriminated. Description of zinc homeostasis-related effects on the activation of key signaling molecules, as well as on epigenetic modifications, are included to emphasize the role of zinc as a gatekeeper of immune function.

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“…We found a small but significant negative association between type 1 diabetes and lead in soil in our EnWAS and Bayesian analyses, although this association did not remain significant in the multivariable ecological regression. A study in Sardinia reported a significant negative correlation between type 1 diabetes incidence rates and lead in stream sediments [42].…”

Section: Discussionmentioning

confidence: 98%

Childhood type 1 diabetes: an environment-wide association study across England

et al. 2020

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Aims/hypothesis Type 1 diabetes is an autoimmune disease affecting~400,000 people across the UK. It is likely that environmental factors trigger the disease process in genetically susceptible individuals. We assessed the associations between a wide range of environmental factors and childhood type 1 diabetes incidence in England, using an agnostic, ecological environmentwide association study (EnWAS) approach, to generate hypotheses about environmental triggers. Methods We undertook analyses at the local authority district (LAD) level using a national hospital episode statistics-based incident type 1 diabetes dataset comprising 13,948 individuals with diabetes aged 0-9 years over the period April 2000 to March 2011. We compiled LAD level estimates for a range of potential demographic and environmental risk factors including meteorological, land use and environmental pollution variables. The associations between type 1 diabetes incidence and risk factors were assessed via Poisson regression, disease mapping and ecological regression. Results Case counts by LAD varied from 1 to 236 (median 33, interquartile range 24-46). Overall type 1 diabetes incidence was 21.2 (95% CI 20.9, 21.6) per 100,000 individuals. The EnWAS and disease mapping indicated that 15 out of 53 demographic and environmental risk factors were significantly associated with diabetes incidence, after adjusting for multiple testing. These included air pollutants (particulate matter, nitrogen dioxide, nitrogen oxides, carbon monoxide; all inversely associated), as well as lead in soil, radon, outdoor light at night, overcrowding, population density and ethnicity. Disease mapping revealed spatial heterogeneity in type 1 diabetes risk. The ecological regression found an association between type 1 diabetes and the living environment domain of the Index of Multiple Deprivation (RR 0.995; 95% credible interval [CrI] 0.991, 0.998) and radon potential class (RR 1.044; 95% CrI 1.015, 1.074). Conclusions/interpretation Our analysis identifies a range of demographic and environmental factors associated with type 1 diabetes in children in England.

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Zinc and Other Metals Deficiencies and Risk of Type 1 Diabetes: An Ecological Study in the High Risk Sardinia Island

Cited by 27 publications

References 41 publications

Zinc Status and Risk of Cardiovascular Diseases and Type 2 Diabetes Mellitus—A Systematic Review of Prospective Cohort Studies

Zinc Status and Risk of Cardiovascular Diseases and Type 2 Diabetes Mellitus—A Systematic Review of Prospective Cohort Studies

Zinc as a Gatekeeper of Immune Function

Childhood type 1 diabetes: an environment-wide association study across England

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