Dataset Information

Glucose Metabolism Effects of Vitamin D in Prediabetes: The VitDmet Randomized Placebo-Controlled Supplementation Study.

ABSTRACT: Epidemiological evidence suggests a role for vitamin D in type 2 diabetes prevention. We investigated the effects of vitamin D3 supplementation on glucose metabolism and inflammation in subjects with prediabetes. A 5-month randomized, double-blind, placebo-controlled intervention with three arms (placebo, 40 ?g/d, or 80 ?g/d vitamin D3) was carried out among sixty-eight overweight (BMI 25-35) and aging (?60 years) subjects from Finland, with serum 25-hydroxyvitamin D3 [25(OH)D3] < 75 nmol/L and either impaired fasting glucose or impaired glucose tolerance. Analyses included 66 subjects who completed the trial. Glucose metabolism was evaluated by fasting and 2-hour oral glucose tolerance test-derived indices and glycated hemoglobin. Inflammation was evaluated by high-sensitive C-reactive protein and five cytokines. Although a dose-dependent increase in serum 25(OH)D3 over the supplementation period was observed (P trend < 0.001), there were no other statistically significant differences in changes in the 13 glucose homeostasis indicators between the study groups other than increase in the 120 min glucose concentration (P trend = 0.021) and a decreasing trend both in 30 min plasma insulin (P trend = 0.030) and glycated hemoglobin (P trend = 0.024) concentrations. A borderline statistically significant decreasing trend in interleukin-1 receptor antagonist concentration was observed (P = 0.070). Vitamin D3 supplementation does not improve glucose metabolism in ageing subjects with prediabetes but may have modest anti-inflammatory effects.

SUBMITTER: Tuomainen TP

PROVIDER: S-EPMC4461773 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Glucose Metabolism Effects of Vitamin D in Prediabetes: The VitDmet Randomized Placebo-Controlled Supplementation Study.

Tuomainen Tomi-Pekka TP Virtanen Jyrki K JK Voutilainen Sari S Nurmi Tarja T Mursu Jaakko J de Mello Vanessa D F VD Schwab Ursula U Hakumäki Martti M Pulkki Kari K Uusitupa Matti M

Journal of diabetes research 20150527

Epidemiological evidence suggests a role for vitamin D in type 2 diabetes prevention. We investigated the effects of vitamin D3 supplementation on glucose metabolism and inflammation in subjects with prediabetes. A 5-month randomized, double-blind, placebo-controlled intervention with three arms (placebo, 40 μg/d, or 80 μg/d vitamin D3) was carried out among sixty-eight overweight (BMI 25-35) and aging (≥60 years) subjects from Finland, with serum 25-hydroxyvitamin D3 [25(OH)D3] < 75 nmol/L and ...[more]

PMID: 26106626

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Project description:Adding supraphysiologic doses of levothyroxine (L-T4) to standard treatment for bipolar depression shows promise, but the mechanisms underlying clinical improvement are unknown. In a previous pilot study, L-T4 treatment reduced depression scores and activity within the anterior limbic network. Here we extended this work in a randomized, double-blind, placebo-controlled study of patients with bipolar depression. Cerebral glucose metabolism was assessed with positron emission tomography and [F-18]fluorodeoxyglucose before and after 6 weeks of treatment with L-T4 (n=15) or placebo (n=10) in 12 volumes of interest (VOIs): the bilateral thalamus, amygdala, hippocampus, dorsal striatum and ventral striatum, and midline cerebellar vermis and subgenual cingulate cortex. Radioactivity in the VOIs, normalized to whole-brain radioactivity was taken as a surrogate index of glucose metabolism, and markers of thyroid function were assayed. Changes in brain activity and their association with clinical response were assessed using statistical parametric mapping. Adjunctive L-T4 treatment produced a significant decline in depression scores during the 6-week treatment. In patients treated with L-T4, we found a significant decrease in regional activity at P<0.05 after Bonferroni correction in the left thalamus, right amygdala, right hippocampus, left ventral striatum and the right dorsal striatum. Decreases in the left thalamus, left dorsal striatum and the subgenual cingulate were correlated with a reduction in depression scores (P<0.05 after Bonferroni correction). Placebo treatment was associated with a significant decrease in activity only in the right amygdala, and no region had a change in activity that was correlated with change in depression scores. The groups differed significantly in the relationship between the changes in depression scores and in activity in the thalamus bilaterally and the left ventral striatum. The findings provide evidence that administration of supraphysiologic thyroid hormone improves depressive symptoms in patients with bipolar disorder by modulating function in components of the anterior limbic network.

Project description:BACKGROUND:Vitamin D deficiency has been associated with multiple diseases, but the causal relevance and underlying processes are not fully understood. Elucidating the mechanisms of action of drug treatments in humans is challenging, but application of functional genomic approaches in randomized trials may afford an opportunity to systematically assess molecular responses. METHODS:In the Biochemical Efficacy and Safety Trial of Vitamin D (BEST-D), a double-blind, placebo-controlled, dose-finding, randomized clinical trial, 305 community-dwelling individuals aged over 65?years were randomly allocated to treatment with vitamin D3 4000?IU, 2000?IU or placebo daily for 12?months. Genome-wide genotypes at baseline, and transcriptome and plasma levels of cytokines (IFN-?, IL-10, IL-8, IL-6 and TNF-?) at baseline and after 12?months, were measured. The trial had >90% power to detect 1.2-fold changes in gene expression. FINDINGS:Allocation to vitamin D for 12-months was associated with 2-fold higher plasma levels of 25-hydroxy-vitamin D (25[OH]D, 4000?IU regimen), but had no significant effect on whole-blood gene expression (FDR?<?5%) or on plasma levels of cytokines compared with placebo. In pre-specified analysis, rs7041 (intron variant, GC) had a significant effect on circulating levels of 25(OH)D in the low dose, but not in the placebo or high dose vitamin D regimen. A gene expression quantitative trait locus analysis (eQTL) demonstrated evidence of 31,568 cis-eQTLs (unique SNP-probe pairs) among individuals at baseline and 34,254 after supplementation for 12?months (any dose). No significant associations involving vitamin D supplementation response eQTLs were found. INTERPRETATION:We performed a comprehensive functional genomics and molecular analysis of vitamin D supplementation in a randomized, placebo-controlled trial. Although this study was limited to mostly Caucasian individuals aged over 65?years, the results differ from many previous studies and do not support a strong effect of vitamin D on long-term transcriptomic changes in blood or on plasma cytokine levels. The trial demonstrates the feasibility of applying functional genomic and genetic approaches in randomized trials to assess molecular and individual level responses. KEY RESULT:Supplementation with high-dose vitamin D in older people for 12?months in a randomized, placebo-controlled trial had no significant effect on gene expression or on plasma concentrations of selected cytokines. TRIAL REGISTRATION:SRCTN registry (Number 07034656) and the European Clinical Trials Database (EudraCT Number 2011-005763-24).

Dataset Information

Glucose Metabolism Effects of Vitamin D in Prediabetes: The VitDmet Randomized Placebo-Controlled Supplementation Study.

Publications

Glucose Metabolism Effects of Vitamin D in Prediabetes: The VitDmet Randomized Placebo-Controlled Supplementation Study.

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