A randomized trial of selenium supplementation and risk of type-2 diabetes, as assessed by plasma adiponectin

Background: Evidence that selenium affects the risk of type-2 diabetes is conflicting, with observational studies and a few randomized trials showing both lower and higher risk linked to the level of selenium intake and status. We investigated the effect of selenium supplementation on the risk of type-2 diabetes in a population of relatively low selenium status as part of the UK PRECISE (PREvention of Cancer by Intervention with SElenium) pilot study. Plasma adiponectin concentration, a recognised independent predictor of type-2 diabetes risk and known to be correlated with circulating selenoprotein P, was the biomarker chosen. Methods: In a randomized, double-blind, placebo-controlled trial, five hundred and one elderly volunteers were randomly assigned to a six-month intervention with 100, 200 or 300 μg selenium/d as high-selenium or placebo yeast. Adiponectin concentration was measured by ELISA at baseline and after six months of treatment in 473 participants with one or both plasma samples available. Results: Mean (SD) plasma selenium concentration was 88.5 ng/g (19.1) at baseline and increased significantly in the selenium-treatment groups. In baseline cross-sectional analyses, the fully adjusted geometric mean of plasma adiponectin was 14% lower (95% CI, 0-27%) in the highest than in the lowest quartile of plasma selenium (P for linear trend = 0.04). In analyses across randomized groups, however, selenium supplementation had no effect on adiponectin levels after six months of treatment (P = 0.96). Conclusions: These findings are reassuring as they did not show a diabetogenic effect of a six-month supplementation with selenium in this sample of elderly individuals of relatively low selenium status

Cross-sectional association between plasma selenium and adiponectin concentrations at baseline^*

*<p>Results were obtained from linear regression models of log-transformed adiponectin levels on selenium levels using only cross-sectional data from the</p><p>baseline visit.</p>†<p>Model 1 adjusted for age (continuous), sex, and study center (Bungay, Guisborough, Bromsgrove, or Linthorpe).</p>‡<p>Model 2 further adjusted for smoking status (never, former, or current), drinking habits (never, former, or current), body mass index (continuous), and waist circumference (continuous).</p>§<p>Model 3 further adjusted for total cholesterol level (continuous), HDL cholesterol level (continuous), use of lipid lowering medications, and use of diabetes medications.</p><p>∥<i>P</i> values for linear trend were obtained from Wald tests for the coefficient of an ordinal variable with the median baseline selenium level of each quartile in linear regression models.</p

Descriptive baseline characteristics overall and by treatment group^*

*<p>Data are means (SDs) or numbers (%) in participants with at least one adiponectin measurement available either at baseline or at six months.</p>†<p><i>P</i> values for homogeneity of means or proportions across the four treatment groups, as obtained from one-way analysis-of-variance <i>F</i> tests for continuous variables and Pearson’s chi-squared tests for categorical variables.</p><p>HDL, high-density lipoprotein.</p

Effect of selenium supplementation on changes in plasma adiponectin and selenium concentrations after six months^*

*<p>Results were obtained from linear mixed models on log-transformed adiponectin levels (and untransformed selenium levels) with fixed treatment-by-time interactions and random between-subject variations in both baseline levels (intercepts) and longitudinal changes over time (slopes).</p>†<p><i>P</i> values comparing the ratio of geometric mean adiponectin levels (and the change in arithmetic mean selenium levels) at six months to baseline in each active treatment group to placebo, as obtained from Wald tests for each treatment-by-time interaction coefficient in linear mixed models.</p>‡<p>Overall <i>P</i> value comparing the three active treatment groups to placebo, as obtained from the joint Wald test for all treatment-by-time interaction coefficients in linear mixed models.</p