Selenium supplementation and insulin resistance in a randomized, clinical trial

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Abstract

Objective

While controversial, observational and randomized clinical trial data implicate the micronutrient selenium (Se) in the development of type 2 diabetes (T2D). The aim of this study was to test the hypothesis that Se supplementation adversely affects pancreatic β-cell function and insulin sensitivity.

Research design and methods

In a subset of 400 individuals participating in a randomized, placebo-controlled trial of Se at 200 µg/day for colorectal adenomatous polyps, fasting plasma glucose and insulin were measured before randomization and within 6 months of completing intervention. Change in the homeostasis model assessment-β cell function (HOMA2-%β) and insulin sensitivity (HOMA2-%S) were compared between arms. A subgroup of 175 (79 Se and 96 placebo) participants underwent a modified oral glucose tolerance test (mOGTT) at the end of intervention and change in glucose values was assessed.

Results

No statistically significant differences were observed for changes in HOMA2-%β or HOMA2-%S between those who received Se compared with placebo. After a mean of 2.9 years on study, mean HOMA2-%β values were 3.1±24.0 and 3.1±29.8 for the Se and placebo groups, respectively (p=0.99). For HOMA2-%S, the values were −0.5±223.2 and 80.9±1530.9 for the Se and placebo groups, respectively (p=1.00). Stratification by sex or age did not reveal any statistically significant effects on insulin sensitivity by treatment group. For mOGTT, mean baseline fasting blood glucose concentrations were significantly higher among participants in the placebo group compared with the Se group (96.6±14.6 and 92.3±12.0, respectively; p=0.04), a trend which remained through the 20 min assessment.

Conclusions

These findings do not support a significant adverse effect of daily Se supplementation with 200 µg/day of selenized yeast on β-cell function or insulin sensitivity as an explanation for previously reported associations between Se and T2D. Further clarification of longer term effects of Se is needed.

Clinical trial registry

NIH Clinical Trials.gov number NCT00078897.

Related collections

Most cited references 17

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From selenium to selenoproteins: synthesis, identity, and their role in human health.

Laura Vanda Papp, Jun Lu, Arne Holmgren … (2007)

The requirement of the trace element selenium for life and its beneficial role in human health has been known for several decades. This is attributed to low molecular weight selenium compounds, as well as to its presence within at least 25 proteins, named selenoproteins, in the form of the amino acid selenocysteine (Sec). Incorporation of Sec into selenoproteins employs a unique mechanism that involves decoding of the UGA codon. This process requires multiple features such as the selenocysteine insertion sequence (SECIS) element and several protein factors including a specific elongation factor EFSec and the SECIS binding protein 2, SBP2. The function of most selenoproteins is currently unknown; however, thioredoxin reductases (TrxR), glutathione peroxidases (GPx) and thyroid hormone deiodinases (DIO) are well characterised selenoproteins involved in redox regulation of intracellular signalling, redox homeostasis and thyroid hormone metabolism. Recent evidence points to a role for selenium compounds as well as selenoproteins in the prevention of some forms of cancer. A number of clinical trials are either underway or being planned to examine the effects of selenium on cancer incidence. In this review we describe some of the recent progress in our understanding of the mechanism of selenoprotein synthesis, the role of selenoproteins in human health and disease and the therapeutic potential of some of these proteins.

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Reactive oxygen species enhance insulin sensitivity.

Kim Loh, Haiyang Deng, Atsushi Fukushima … (2009)

Chronic reactive oxygen species (ROS) production by mitochondria may contribute to the development of insulin resistance, a primary feature of type 2 diabetes. In recent years it has become apparent that ROS generation in response to physiological stimuli such as insulin may also facilitate signaling by reversibly oxidizing and inhibiting protein tyrosine phosphatases (PTPs). Here we report that mice lacking one of the key enzymes involved in the elimination of physiological ROS, glutathione peroxidase 1 (Gpx1), were protected from high-fat-diet-induced insulin resistance. The increased insulin sensitivity in Gpx1(-/-) mice was attributed to insulin-induced phosphatidylinositol-3-kinase/Akt signaling and glucose uptake in muscle and could be reversed by the antioxidant N-acetylcysteine. Increased insulin signaling correlated with enhanced oxidation of the PTP family member PTEN, which terminates signals generated by phosphatidylinositol-3-kinase. These studies provide causal evidence for the enhancement of insulin signaling by ROS in vivo.

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Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group.

S. Davis, H. Park, Marisa Sanders … (1996)

To determine whether a nutritional supplement of selenium will decrease the incidence of cancer. A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial. Seven dermatology clinics in the eastern United States. A total of 1312 patients (mean age, 63 years; range, 18-80 years) with a history of basal cell or squamous cell carcinomas of the skin were randomized from 1983 through 1991. Patients were treated for a mean (SD) of 4.5 (2.8) years and had a total follow-up of 6.4 (2.0) years. Oral administration of 200 microg of selenium per day or placebo. The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin. The secondary end points, established in 1990, were all-cause mortality and total cancer mortality, total cancer incidence, and the incidences of lung, prostate, and colorectal cancers. After a total follow-up of 8271 person-years, selenium treatment did not significantly affect the incidence of basal cell or squamous cell skin cancer. There were 377 new cases of basal cell skin cancer among patients in the selenium group and 350 cases among the control group (relative risk [RR], 1.10; 95% confidence interval [CI], 0.95-1.28), and 218 new squamous cell skin cancers in the selenium group and 190 cases among the controls (RR, 1.14; 95% CI, 0.93-1.39). Analysis of secondary end points revealed that, compared with controls, patients treated with selenium had a nonsignificant reduction in all-cause mortality (108 deaths in the selenium group and 129 deaths in the control group [RR; 0.83; 95% CI, 0.63-1.08]) and significant reductions in total cancer mortality (29 deaths in the selenium treatment group and 57 deaths in controls [RR, 0.50; 95% CI, 0.31-0.80]), total cancer incidence (77 cancers in the selenium group and 119 in controls [RR, 0.63; 95% CI, 0.47-0.85]), and incidences of lung, colorectal, and prostate cancers. Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group, the blinded phase of the trial was stopped early. No cases of selenium toxicity occurred. Selenium treatment did not protect against development of basal or squamous cell carcinomas of the skin. However, results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites. These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made

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Author and article information

Journal

Journal ID (nlm-ta): BMJ Open Diabetes Res Care

Journal ID (iso-abbrev): BMJ Open Diabetes Res Care

Journal ID (hwp): bmjdrc

Journal ID (publisher-id): bmjdrc

Title: BMJ Open Diabetes Research & Care

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Electronic): 2052-4897

Publication date Collection: 2019

Publication date (Electronic): 7 February 2019

Volume: 7

Issue: 1

Electronic Location Identifier: e000613

Affiliations

[1 ] departmentDepartment of Epidemiology and Biostatistics , Mel and Enid Zuckerman College of Public Health, University of Arizona , Tucson, Arizona

[2 ] University of Arizona Cancer Center , Tucson, Arizona

[3 ] departmentDepartment of Nutritional Sciences , University of Arizona , Tucson, Arizona

[4 ] departmentDepartment of Medicine , University of Arizona , Tucson, Arizona

[5 ] Center for Disparities in Diabetes, Obesity and Metabolism, University of Arizona , Tucson, Arizona

[6 ] departmentDepartment of Surgery , University of Arizona , Tucson, Arizona

[7 ] departmentDepartment of Medicine , Stony Brook University , New York City, New York, USA

Author notes

[Correspondence to ] Dr Elizabeth Theresa Jacobs; jacobse@ 123456email.arizona.edu

Article

Publisher ID: bmjdrc-2018-000613

DOI: 10.1136/bmjdrc-2018-000613

PMC ID: 6398811

PubMed ID: 30899530

SO-VID: 27c7e4db-6fc0-43e4-9de7-4dca7911d9b1

License:

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

History

Date received : 28 August 2018

Date revision received : 13 December 2018

Date accepted : 22 December 2018

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000054, National Cancer Institute;

Award ID: P01CA041108

Award ID: P30CA023074

Award ID: R01CA151708

Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: R01DK047396

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Keywords: selenium,supplementation,insulin resistance,homa,homeostatic model assessment,ogtt

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Keywords: selenium, supplementation, insulin resistance, homa, homeostatic model assessment, ogtt

Selenium supplementation and insulin resistance in a randomized, clinical trial

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Abstract

Objective

Research design and methods

Results

Conclusions

Clinical trial registry

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Karger: Nutrition and Dietetics

Most cited references 17

From selenium to selenoproteins: synthesis, identity, and their role in human health.

Reactive oxygen species enhance insulin sensitivity.

Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group.

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