A randomized, placebo-controlled trial of vitamin D supplementation to improve glycaemia in overweight and obese African Americans.

Vitamin D deficiency may increase the risk for type 2 diabetes. African Americans tend to have poor vitamin D status and increased risk of diabetes, but effects of vitamin D supplementation on components of diabetes risk have not been tested in this group. This study was conducted to determine whether vitamin D supplementation improves insulin secretion, insulin sensitivity and glycaemia in African Americans with prediabetes or early diabetes. In this randomized, placebo-controlled trial, we examined the effect of 4000 IU/day vitamin D(3,) on glycaemia and contributing measures including insulin secretion, insulin sensitivity and the disposition index over 12 weeks in 89 overweight or obese African Americans with prediabetes or early diabetes. Outcome measures were derived from oral glucose tolerance testing. Mean plasma 25-hydroxyvitamin D was about 40 nmol/l in the placebo and vitamin D groups at baseline and increased to 81 nmol/l with supplementation. Insulin sensitivity decreased by 4% in the vitamin D group compared with a 12% increase in the placebo group (p = 0.034). Insulin secretion increased by 12% in the vitamin D group compared with a 2% increase in the placebo group (p = 0.024), but changes in the disposition index were similar across groups. There was no effect of supplementation on post-load glucose or other measures of glycaemia. Supplementation with 4000 IU/day vitamin D(3) successfully corrected vitamin D insufficiency and had divergent effects on insulin secretion and sensitivity with no overall effect on disposition index or glycaemia. In this study, vitamin D supplementation for 3 months did not change the pathophysiology of prediabetes in overweight and obese African Americans.

Harris SS ，Pittas AG ，Palermo NJ 《-》

Vitamin D supplementation has no effect on insulin sensitivity or secretion in vitamin D-deficient, overweight or obese adults: a randomized placebo-controlled trial.

Background: Vitamin D supplementation has been proposed as a potential strategy to prevent type 2 diabetes. Existing clinical trials have been limited by short duration, low doses of vitamin D, variability in participants' vitamin D-deficiency status, and the use of surrogate measures of body composition, insulin sensitivity, and insulin secretion.Objective: To address existing knowledge gaps, we conducted a double-blind, randomized, placebo-controlled trial to investigate whether vitamin D supplementation that is provided in a sufficient dose and duration to vitamin D-deficient individuals would improve insulin sensitivity or secretion as measured with the use of gold-standard methods. We hypothesized that vitamin D supplementation would improve insulin sensitivity and secretion compared with placebo.Design: Sixty-five overweight or obese, vitamin D-deficient (25-hydroxyvitamin D [25(OH)D] concentration ≤50 nmol/L) adults were randomly assigned to receive either a bolus oral dose of 100,000 IU cholecalciferol followed by 4000 IU cholecalciferol/d or a matching placebo for 16 wk. Before and after the intervention, participants received gold-standard assessments of body composition (via dual X-ray absorptiometry), insulin sensitivity (via hyperinsulinemic-euglycemic clamps), and insulin secretion [via intravenous-glucose-tolerance tests (IVGTTs)].Results: Fifty-four participants completed the study [35 men and 19 women; mean ± SD age: 31.9 ± 8.5 y; body mass index (in kg/m2): 30.9 ± 4.4]. 25(OH)D increased with vitamin D supplementation compared with placebo (57.0 ± 21.3 compared with 1.9 ± 15.1 nmol/L, respectively; P = 0.02). Vitamin D and placebo groups did not differ in change in insulin sensitivity (0.02 ± 2.0 compared with -0.03 ± 2.8 mg · kg-1 · min-1, respectively; P = 0.9) or first-phase insulin secretion (-21 ± 212 compared with 24 ± 184 mU/L, respectively; P = 0.9). Results remained nonsignificant after adjustment for age, sex, percentage of body fat, sun exposure, physical activity, and dietary vitamin D intake (P > 0.1).Conclusions: Vitamin D supplementation does not improve insulin sensitivity or secretion in vitamin D-deficient, overweight or obese adults, despite using high-dose vitamin D supplementation and robust endpoint measures. Therefore, it is unlikely that vitamin D supplementation would be an effective strategy for reducing diabetes risk even in vitamin D-deficient populations. This trial was registered at clinicaltrials.gov as NCT02112721.

Mousa A ，Naderpoor N ，de Courten MP ，Teede H ，Kellow N ，Walker K ，Scragg R ，de Courten B ... -  《-》

Effect of moderate-dose vitamin D supplementation on insulin sensitivity in vitamin D-deficient non-Western immigrants in the Netherlands: a randomized placebo-controlled trial.

Low serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with insulin resistance, the metabolic syndrome, and type 2 diabetes. Because many non-Western immigrants in the Netherlands are vitamin D deficient, obese, and at high risk of diabetes, vitamin D supplementation may contribute to prevent diabetes and insulin resistance. We examined the effect of vitamin D supplementation on insulin sensitivity and β cell function in overweight, vitamin D-deficient, non-Western immigrants at high risk of diabetes. The study was a 16-wk, randomized, placebo-controlled trial. A total of 130 non-Western immigrants with prediabetes (fasting glucose concentration >5.5 mmol/L or random glucose concentration from 7.8 to 11.1 mmol/L) and vitamin D deficiency (serum 25[OH]D concentration <50 nmol/L) were randomly assigned after stratification by sex to receive either cholecalciferol (1200 IU/d) or a placebo for 16 wk. All participants received 500 mg Ca/d as calcium carbonate. The primary outcome was the difference in the area under the curve of insulin and glucose after a 75-g oral-glucose-tolerance test after 4 mo of treatment. Secondary outcomes were insulin-sensitivity variables, β cell-function variables, and metabolic syndrome. Mean serum 25(OH)D concentrations increased significantly in the vitamin D compared with placebo groups. After 4 mo of therapy, the mean between-group difference was 38 nmol/L (95% CI: 32.1, 43.9 nmol/L; P < 0.001). There was no significant effect on insulin sensitivity and β cell function. In a post hoc analysis, when patients with diabetes at baseline were excluded, a significant increase in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L (P = 0.040). Vitamin D supplementation in non-Western vitamin D-deficient immigrants with prediabetes did not improve insulin sensitivity or β cell function or change the incidence of metabolic syndrome. However, after the exclusion of diabetic subjects, an improvement in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L. This trial was registered at trialregister.nl as NTR1827.

Oosterwerff MM ，Eekhoff EM ，Van Schoor NM ，Boeke AJ ，Nanayakkara P ，Meijnen R ，Knol DL ，Kramer MH ，Lips P ... -  《-》

Effects of 6-month vitamin D supplementation on insulin sensitivity and secretion: a randomised, placebo-controlled trial.

Lemieux P ，Weisnagel SJ ，Caron AZ ，Julien AS ，Morisset AS ，Carreau AM ，Poirier J ，Tchernof A ，Robitaille J ，Bergeron J ，Marette A ，Vohl MC ，Gagnon C ... -  《-》

Effects of Vitamin D Supplementation on Insulin Sensitivity and Secretion in Prediabetes.

Vitamin D regulates glucose homeostasis pathways, but effects of vitamin D supplementation on β-cell function remain unclear. To investigate the effects of vitamin D3 supplementation on insulin sensitivity and β-cell function. This is a prespecified secondary analysis of the Vitamin D and Type 2 Diabetes study. Overweight/obese adults at high risk for type 2 diabetes (prediabetes) were randomly treated with vitamin D3 4000 IU or matching placebo daily for 24 months. Disposition index (DI), as an estimate of β-cell function, was calculated as the product of Homeostasis Model Assessment 2 indices derived from C-peptide values (HOMA2%Scpep) and C-peptide response during the first 30 minutes of a 75-g oral glucose tolerance test (OGTT). Mean age was 60.5 ± 9.8 years and body mass index was 31.9 ± 4.4 kg/m2. Mean serum 25(OH)D level increased from 27.9 ± 10.3 ng/mL at baseline to 54.9 ng/mL at 2 years in the vitamin D group and was unchanged (28.5 ± 10.0 ng/mL) in the placebo group. The baseline DI predicted incident diabetes independent of the intervention. In the entire cohort, there were no significant differences in changes in DI, HOMA2%Scpep, or C-peptide response between the 2 groups. Among participants with baseline 25(OH)D level <12 ng/mL, the mean percent differences for DI between the vitamin D and placebo groups was 8.5 (95% CI, 0.2-16.8). Supplementation with vitamin D3 for 24 months did not improve an OGTT-derived index of β-cell function in people with prediabetes not selected based on baseline vitamin D status; however, there was benefit among those with very low baseline vitamin D status.

Rasouli N ，Brodsky IG ，Chatterjee R ，Kim SH ，Pratley RE ，Staten MA ，Pittas AG ，D2d Research Group ... -  《-》