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

Abstract

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. 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. 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)]. Fifty-four participants completed the study [35 men and 19 women; mean ± SD age: 31.9 ± 8.5 y; body mass index (in kg/m): 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; = 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 · min, respectively; = 0.9) or first-phase insulin secretion (-21 ± 212 compared with 24 ± 184 mU/L, respectively; = 0.9). Results remained nonsignificant after adjustment for age, sex, percentage of body fat, sun exposure, physical activity, and dietary vitamin D intake ( > 0.1). 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.

Effect of Vitamin D Supplementation on Obesity‐Induced Insulin Resistance: A Double‐Blind, Randomized, Placebo‐Controlled Trial

“…In a small group of healthy male volunteers ( n = 18), insulin sensitivity, measured using the clamp procedure, was similar after either calcitriol or placebo treatment, but these subjects had normal body weight and vitamin D levels . The findings of a recent randomized controlled trial conducted on subjects with overweight or obesity and with no history of diabetes and vitamin D deficiency contrast with our findings, showing no difference in insulin sensitivity measured with the use of a hyperinsulinemic‐euglycemic clamp and insulin secretion measured with the use of an intravenous glucose tolerance test after vitamin D supplementation compared to placebo, despite a significant increase in 25(OH)D concentrations in the vitamin D group. However, in our study, subjects showed a reduction in body weight following a hypocaloric diet, suggesting that supplementation with vitamin D may have a greater effect than lifestyle intervention alone in improving insulin sensitivity in vitamin D deficient subjects with obesity.…”

Long‐term treatment with metformin in type 2 diabetes and vitaminDlevels:Apost‐hocanalysis of a randomized placebo‐controlled trial

“…Several intervention trials with vitamin D supplementation failed to show significant protection against the onset of diabetes [15][16][17] or improvement of cardiovascular risk, insulin sensitivity and glucose regulation. [18][19][20][21][22] As only 2 of these trials had a vitamin D deficiency (a 25-hydroxyvitamin D [25(OH)D] below 50 nmoL/L) as inclusion criterion, 19,20 more research is needed to draw conclusions about the association between vitamin D deficiency and type 2 diabetes. Studies on the effects of metformin on vitamin D levels are sparse.…”

Sex-Specific Association of Serum 25-Hydroxyvitamin D₃ with Insulin Resistance in Chinese Han Patients with Newly Diagnosed Type 2 Diabetes Mellitus

“…However, the definitive association between vitamin D and T2DM has also been doubted (16,17). Additionally, some Mendelian randomization studies and randomized placebo-controlled trials have challenged the causal association between vitamin D and T2DM (18)(19)(20)(21). (22,23).…”