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      Selenium deficiency is linearly associated with hypoglycemia in healthy adults

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          Abstract

          OBJECTIVE

          The trace element selenium (Se) is needed for regular biosynthesis of selenoproteins, which contribute to antioxidative defense systems and affect redox-regulated signaling. Elevated Se intake and selenoprotein expression levels have been associated with impaired hydrogen peroxide-dependent signaling by insulin, leading to hyperglycemia and insulin resistance. The relation of low Se intake with glucose status and carbohydrate metabolism is poorly known.

          RESEARCH DESIGN AND METHODS

          A cross sectional analysis among healthy subjects residing in two Chinese counties with different habitual Se intakes was conducted. Fasted glucose levels were related to Se concentrations of 5686 adults by linear regression analysis with Se, body mass index, age, thyroid status, insulin and sex as independent variables.

          RESULTS

          Serum Se correlated strongly and positively with glucose in the Se-deficient population. There was no strong relationship of Se and glucose in the non-deficient population. Overt hypoglycemia (serum glucose < 2.8 mM) was observed in 19.2% of this random sample of subjects in the Se-deficient and in 1.4% of the moderately supplied population, respectively.

          CONCLUSIONS

          An adequate Se supply constitutes an important factor for glucose homeostasis in human subjects. The interaction between Se status and glucose control is not limited to hyperglycemia, but apparently extends to hypoglycemia risk in Se deficiency. This newly identified relationship may be of relevance for the course of severe disease including major trauma, sepsis and COVID-19, where Se deficiency has been associated with mortality risk.

          Highlights

          • •

            A cross-sectional study compared serum Se and Glc levels in 5686 healthy adults.

          • •

            Half of the subjects were residing on Se poor soil and displayed Se deficiency.

          • •

            These Se-deficient subjects showed a linear association of serum Se and Glc.

          • •

            A well-matched control population with adequate Se supply showed no such relation.

          • •

            This novel interaction may be relevant for disease and death risk in Se deficiency.

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          A liver-derived secretory protein, selenoprotein P, causes insulin resistance.

          Hirofumi Misu, Toshinari Takamura, Hiroaki Takayama … (2010)
          The liver may regulate glucose homeostasis by modulating the sensitivity/resistance of peripheral tissues to insulin, by way of the production of secretory proteins, termed hepatokines. Here, we demonstrate that selenoprotein P (SeP), a liver-derived secretory protein, causes insulin resistance. Using serial analysis of gene expression (SAGE) and DNA chip methods, we found that hepatic SeP mRNA levels correlated with insulin resistance in humans. Administration of purified SeP impaired insulin signaling and dysregulated glucose metabolism in both hepatocytes and myocytes. Conversely, both genetic deletion and RNA interference-mediated knockdown of SeP improved systemic insulin sensitivity and glucose tolerance in mice. The metabolic actions of SeP were mediated, at least partly, by inactivation of adenosine monophosphate-activated protein kinase (AMPK). In summary, these results demonstrate a role of SeP in the regulation of glucose metabolism and insulin sensitivity and suggest that SeP may be a therapeutic target for type 2 diabetes. Copyright © 2010 Elsevier Inc. All rights reserved.
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            Is Open Access

            Selenium Deficiency Is Associated with Mortality Risk from COVID-19

            Arash A Moghaddam, Raban Arved Heller, Qian Sun … (2020)
            SARS-CoV-2 infections underlie the current coronavirus disease (COVID-19) pandemic and are causative for a high death toll particularly among elderly subjects and those with comorbidities. Selenium (Se) is an essential trace element of high importance for human health and particularly for a well-balanced immune response. The mortality risk from a severe disease like sepsis or polytrauma is inversely related to Se status. We hypothesized that this relation also applies to COVID-19. Serum samples (n = 166) from COVID-19 patients (n = 33) were collected consecutively and analyzed for total Se by X-ray fluorescence and selenoprotein P (SELENOP) by a validated ELISA. Both biomarkers showed the expected strong correlation (r = 0.7758, p < 0.001), pointing to an insufficient Se availability for optimal selenoprotein expression. In comparison with reference data from a European cross-sectional analysis (EPIC, n = 1915), the patients showed a pronounced deficit in total serum Se (mean ± SD, 50.8 ± 15.7 vs. 84.4 ± 23.4 µg/L) and SELENOP (3.0 ± 1.4 vs. 4.3 ± 1.0 mg/L) concentrations. A Se status below the 2.5th percentile of the reference population, i.e., [Se] < 45.7 µg/L and [SELENOP] < 2.56 mg/L, was present in 43.4% and 39.2% of COVID samples, respectively. The Se status was significantly higher in samples from surviving COVID patients as compared with non-survivors (Se; 53.3 ± 16.2 vs. 40.8 ± 8.1 µg/L, SELENOP; 3.3 ± 1.3 vs. 2.1 ± 0.9 mg/L), recovering with time in survivors while remaining low or even declining in non-survivors. We conclude that Se status analysis in COVID patients provides diagnostic information. However, causality remains unknown due to the observational nature of this study. Nevertheless, the findings strengthen the notion of a relevant role of Se for COVID convalescence and support the discussion on adjuvant Se supplementation in severely diseased and Se-deficient patients.
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              Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial.

              R Natarajan, James A R Marshall, Maurizio Trevisan … (2007)
              Findings from animal models suggest that selenium supplementation improves glucose metabolism. To examine the effect of long-term selenium supplementation on the incidence of type 2 diabetes. Secondary analysis of a randomized, double-blind, placebo-controlled trial. Areas of low selenium consumption of the eastern United States. 1202 persons seen in dermatology clinics who did not have type 2 diabetes at baseline. Oral administration of selenium, 200 microg/d, or placebo. Incidence of type 2 diabetes. During an average follow-up of 7.7 years (SD, 2.7), type 2 diabetes developed in 58 selenium recipients and 39 placebo recipients (incidence, 12.6 cases per 1000 person-years vs. 8.4 cases per 1000 person-years, respectively; hazard ratio, 1.55 [95% CI, 1.03 to 2.33]). The lack of benefit of selenium supplementation on the incidence of type 2 diabetes persisted in analyses stratified by age, sex, body mass index, and smoking status. An exposure-response gradient was found across tertiles of baseline plasma selenium level, with a statistically significantly increased risk for type 2 diabetes in the highest tertile of baseline plasma selenium level (hazard ratio, 2.70 [CI, 1.30 to 5.61]). Diabetes was a secondary outcome in the parent trial. Diagnoses of diabetes were self-reported but were validated in most participants. The sample was mostly older and white. Selenium supplementation does not seem to prevent type 2 diabetes, and it may increase risk for the disease. Click here for related information on selenium.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Redox Biol
                Journal ID (iso-abbrev): Redox Biol
                Title: Redox Biology
                Publisher: Published by Elsevier B.V.
                ISSN (Electronic): 2213-2317
                Publication date PMC-release: 1 September 2020
                Publication date (Electronic): 1 September 2020
                Electronic Location Identifier: 101709
                Affiliations
                [a ]Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, China
                [b ]Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, CVK, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, 13353, Berlin, Germany
                [c ]Xi’an Jiaotong University Health Science Center, Xi’an, 710 061, China
                Author notes
                [∗ ]Corresponding author. Charité-Universitätsmedizin Berlin, CVK, Institut für Experimentelle Endokrinologie, 13353, Berlin, Germany
                [∗∗ ]Corresponding author. Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University Health Science Center, Xi’an, 710 061, China.
                [1]

                WY and ER contributed equally

                Article
                Publisher ID: S2213-2317(20)30914-9 Publisher ID: 101709
                DOI: 10.1016/j.redox.2020.101709
                PMC ID: 7462470
                PubMed ID: 32905881
                SO-VID: 188ff382-846d-4a0d-bede-ab9b23a39a7b
                Copyright © © 2020 Published by Elsevier B.V.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 21 July 2020
                Date revision received : 21 August 2020
                Date accepted : 27 August 2020
                Categories
                Subject: Article

                Keywords: selenium,selenoprotein,selenop,gpx,insulin,redox
                Data availability:
                Keywords: selenium, selenoprotein, selenop, gpx, insulin, redox

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