Insulin secretion and sensitivity in healthy adults with low vitamin D are not affected by high-dose ergocalciferol administration: a randomized controlled trial

Abstract

Background: Epidemiologic data suggest that low serum 25-hydroxyvitamin D [25(OH)D] increases insulin resistance and the risk of type 2 diabetes. Few interventional trials have assessed the effect of vitamin D on insulin metabolism, and published results are discordant.

Objective: The goal of this study was to perform a detailed assessment of the effect of ergocalciferol administration on glucose and insulin metabolism in healthy people with low total 25(OH)D(total).

Design: This was a 12-wk, double-blinded, randomized controlled trial. We enrolled 90 healthy volunteers aged 18-45 y with serum 25(OH)D ≤20 ng/mL (by immunoassay) and administered 50,000 IU ergocalciferol/wk or placebo for 12 wk. Primary endpoints were change in first-phase insulin response and insulin sensitivity as measured by intravenous glucose tolerance test. Secondary endpoints included change in homeostasis model assessment of insulin resistance; fasting glucose, insulin, and lipids; body mass index (BMI); and blood pressure.

Results: On-study 25(OH)D(total) was assessed by liquid chromatography-tandem mass spectrometry. In the treated group, 25(OH)D(total) rose from 18 ± 7 to 43 ± 12 ng/mL (P < 0.001) with no change in the placebo group. Despite this increase, at 12 wk, there were no between-group differences in either insulin response or insulin sensitivity; nor were there differences in any measured secondary endpoints. There was no evidence of effect modification by sex, race, glucose tolerance status, baseline 25(OH)D(total), or BMI.

Conclusion: In healthy persons with low 25(OH)D(total), ergocalciferol administration for 12 wk normalizes 25(OH)D(total) but does not improve insulin secretion, insulin sensitivity, or other markers of metabolic health.

Trial registration: ClinicalTrials.gov NCT00491322.

Keywords: diabetes; ergocalciferol; glucose; insulin; insulin resistance; vitamin D.

FIGURE 1

Flow diagram of study subjects. OGTT, oral-glucose-tolerance test; 25(OH)D_total, total 25-hydroxyvitamin D.

FIGURE 2

Mean ± SEM changes in 25(OH)D_total (A) and HOMA-IR (B) with ergocalciferol administration. Open squares: placebo group (n = 50); filled squares: ergocalciferol group (n = 40). P values are for between-group comparisons by repeated-measures ANOVA (A) or by ANOVA of AUC (B). 25(OH)D_total, total 25-hydroxyvitamin D.

FIGURE 3

Mean ± SEM changes in first-phase insulin secretory response (mU ^· L^{−1 ·} min/mmol ^· L⁻¹) (A) and insulin sensitivity (min⁻¹/mU⁻¹ · min) (B) as measured by IVGTT with ergocalciferol administration (30). Open squares: placebo group (n = 50); filled squares: ergocalciferol group (n = 40). P values are for between-group difference in change in insulin secretion (A) or insulin sensitivity (B) by ANCOVA with control for baseline value. IVGTT, intravenous-glucose-tolerance test.