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

Chiara M A Cefalo, Caterina Conte, Gian Pio Sorice, Simona Moffa, Vinsin A Sun, Francesca Cinti, Enrica Salomone, Giovanna Muscogiuri, Alex A G Brocchi, Alfredo Pontecorvi, Teresa Mezza, Andrea Giaccari, Chiara M A Cefalo, Caterina Conte, Gian Pio Sorice, Simona Moffa, Vinsin A Sun, Francesca Cinti, Enrica Salomone, Giovanna Muscogiuri, Alex A G Brocchi, Alfredo Pontecorvi, Teresa Mezza, Andrea Giaccari

Abstract

Objective: The aim was to investigate whether vitamin D supplementation, combined with a hypocaloric diet, could have an independent effect on insulin sensitivity in subjects with both overweight and hypovitaminosis D. Changes from baseline in anthropometric parameters, body composition, glucose tolerance, and insulin secretion were considered as secondary outcomes.

Methods: Eighteen volunteers who were nondiabetic and vitamin D deficient and had BMI > 25 kg/m2 were randomized (1:1) in a double-blind manner to a hypocaloric diet + either oral cholecalciferol at 25,000 IU/wk or placebo for 3 months. Hyperinsulinemic-euglycemic clamp to measure insulin sensitivity was performed at baseline and after intervention.

Results: Body weight in both groups decreased significantly (-7.5% in the vitamin D group and -10% in the placebo group; P < 0.05 for both), with no between-group differences. Serum 25-hydroxyvitamin D levels in the vitamin D group increased considerably (from 36.7 ± 13.2 nmol/L to 74.8 ± 18.7 nmol/L; P < 0.001). Insulin sensitivity in the vitamin D group improved (from 4.6 ± 2.0 to 6.9 ± 3.3 mg·kg-1 ·min-1 ; P < 0.001), whereas no changes were observed in the placebo group (from 4.9 ± 1.1 to 5.1 ± 0.3 mg·kg-1 ·min-1 ; P = 0.84).

Conclusions: Cholecalciferol supplementation, combined with a weight loss program, significantly improves insulin sensitivity in healthy subjects with obesity and might represent a personalized approach for insulin-resistant subjects with obesity.

Trial registration: ClinicalTrials.gov NCT02020694.

© 2018 The Authors. Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).

Figures

Figure 1
Figure 1
(A) Body weight and (B) 25‐hydroxyvitamin D (25[OH]D) levels at baseline (black bars) and after 3 months of treatment (white bars); *P < 0.001.
Figure 2
Figure 2
Insulin sensitivity (glucose uptake) at baseline (black bars) and after 3 months of treatment (white bars) in the placebo (PLA) and vitamin D (VITD) groups; *P = 0.02.
Figure 3
Figure 3
Areas under the curve (AUC) for (A) glycemia and, (B) insulin and (C) glucose and (D) insulin curves during oral glucose tolerance tests at baseline and after 3 months of treatment in both groups.

References

    1. Forouhi NG, Luan J, Cooper A, Boucher BJ, Wareham NJ. Baseline serum 25‐hydroxy vitamin D is predictive of future glycemic status and insulin resistance: the Medical Research Council Ely Prospective Study 1990‐2000. Diabetes 2008;57:2619‐2625.
    1. Kayaniyil S, Vieth R, Retnakaran R, et al. Association of vitamin D with insulin resistance and beta‐cell dysfunction in subjects at risk for type 2 diabetes. Diabetes Care 2010;33:1379‐1381.
    1. Pereira‐Santos M, Costa PR, Assis AM, Santos CA, Santos DB. Obesity and vitamin D deficiency: a systematic review and meta‐analysis. Obes Rev 2015;16:341‐349.
    1. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 2000;72:690‐693.
    1. Wamberg L, Christiansen T, Paulsen SK, et al. Expression of vitamin D‐metabolizing enzymes in human adipose tissue‐the effect of obesity and diet‐induced weight loss. Int J Obes (Lond) 2012;37:651‐657.
    1. Barchetta I, De Bernardinis M, Capoccia D, et al. Hypovitaminosis D is independently associated with metabolic syndrome in obese patients. PLoS One 2013;31;8:e68689. doi:10.1371/journal.pone.0068689
    1. Olson ML, Maalouf NM, Oden JD, White PC, Hutchison MR. Vitamin D deficiency in obese children and its relationship to glucose homeostasis. J Clin Endocrinol Metab 2012;97:279‐285.
    1. Kayaniyil S, Retnakaran R, Harris SB, et al. Prospective associations of vitamin D with beta‐cell function and glycemia: the prospective Metabolism and Islet cell Evaluation (PROMISE) cohort study. Diabetes 2011;60:2947‐2953.
    1. Dunlop TW, Vaisanen S, Frank C, Molnar F, Sinkkonen L, Carlberg C. The human peroxisome proliferator‐activated receptor delta gene is a primary target of 1alpha,25‐dihydroxyvitamin D3 and its nuclear receptor. J Mol Biol 2005;349:248‐260.
    1. Maiti A, Beckman MJ. Extracellular calcium is a direct effecter of VDR levels in proximal tubule epithelial cells that counter‐balances effects of PTH on renal Vitamin D metabolism. J Steroid Biochem Mol Biol 2007;103:504‐508.
    1. Dutta D, Mondal SA, Choudhuri S, et al. Vitamin‐D supplementation in prediabetes reduced progression to type 2 diabetes and was associated with decreased insulin resistance and systemic inflammation: an open label randomized prospective study from Eastern India. Diabetes Res Clin Pract 2014;103:e18‐e23.
    1. Muscogiuri G, Sorice GP, Prioletta A, et al. 25‐Hydroxyvitamin D concentration correlates with insulin‐sensitivity and BMI in obesity. Obesity (Silver Spring) 2010;18:1906‐1910.
    1. Grimnes G, Figenschau Y, Almas B, Jorde R. Vitamin D, insulin secretion, sensitivity, and lipids: results from a case‐control study and a randomized controlled trial using hyperglycemic clamp technique. Diabetes 2011;60:2748‐2757.
    1. von Hurst PR, Stonehouse W, Coad J. Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient ‐ a randomised, placebo‐controlled trial. Br J Nutr 2010;103:549‐555.
    1. George PS, Pearson ER, Witham MD. Effect of vitamin D supplementation on glycaemic control and insulin resistance: a systematic review and meta‐analysis. Diabet Med 2012;29:e142‐e150.
    1. Gulseth HL, Wium C, Angel K, Eriksen EF, Birkeland KI. Effects of vitamin D supplementation on insulin sensitivity and insulin secretion in subjects with type 2 diabetes and vitamin D deficiency: a randomized controlled trial. Diabetes Care 2017;40:872‐878.
    1. Kampmann U, Mosekilde L, Juhl C, et al. Effects of 12 weeks high dose vitamin D3 treatment on insulin sensitivity, beta cell function, and metabolic markers in patients with type 2 diabetes and vitamin D insufficiency ‐ a double‐blind, randomized, placebo‐controlled trial. Metabolism 2014;63:1115‐1124.
    1. Fliser D, Stefanski A, Franek E, Fode P, Gudarzi A, Ritz E. No effect of calcitriol on insulin‐mediated glucose uptake in healthy subjects. Eur J Clin Invest 1997;27:629‐633.
    1. Mousa A, Naderpoor N, de Courten MP, et al. Vitamin D supplementation has no effect on insulin sensitivity or secretion in vitamin D‐deficient, overweight or obese adults: a randomized placebo‐controlled trial. Am J Clin Nutr 2017;105:1372‐1381.
    1. Liu P, Ma F, Lou H, Liu Y. The utility of fat mass index vs. body mass index and percentage of body fat in the screening of metabolic syndrome. BMC Public Health 2013;13:629. doi:10.1186/1471-2458-13-629
    1. Mason C, Xiao L, Imayama I, et al. A. Vitamin D3 supplementation during weight loss: a double‐blind randomized controlled trial. Am J Clin Nutr 2014;99:1015‐1025.
    1. Salehpour A, Hosseinpanah F, Shidfarf F, et al. A 12‐week double‐blind randomized clinical trial of vitamin D3 supplementation on body fat mass in healthy overweight and obese women. Nutr J 2012;11:78. doi:10.1186/1475-2891-11-78
    1. Marcotorchino J, Tourniaire F, Astier J, et al. Vitamin D protects against diet‐induced obesity by enhancing fatty acid oxidation. J Nutr Biochem 2014;25:1077‐1083.
    1. Kim JH, Kang S, Jung YN, Choi HS. Cholecalciferol inhibits lipid accumulation by regulating early adipogenesis in cultured adipocytes and zebrafish. Biochembiophys Res Commun 2016;469:646‐653.
    1. Khan RJ, Riestra P, Gebreab SY, et al. Vitamin D receptor gene polymorphisms are associated with abdominal visceral adipose tissue volume and serum adipokine concentrations but not with body mass index or waist circumference in African Americans: the Jackson Heart Study. J Nutr 2016;146:1476‐1482.
    1. Williams PF, Caterson ID, Cooney GJ, Zilkens RR, Turtle JR. High affinity insulin binding and insulin receptor‐effector coupling: modulation by Ca2+. Cell Calcium 1990;11:547‐556.
    1. Rock CL, Emond JA, Flatt SW, et al. Weight loss is associated with increased serum 25‐hydroxyvitamin D in overweight or obese women. Obesity (Silver Spring) 2012;20:2296‐2301.
    1. Thibault V, Morisset AS, Brown C, et al. The increase in serum 25‐hydroxyvitamin D following weight loss does not contribute to the improvement in insulin sensitivity, insulin secretion and beta‐cell function. Br J Nutr 2015;114:161‐168.
    1. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266‐281.
    1. Jorde R, Figenschau Y. Supplementation with cholecalciferol does not improve glycaemic control in diabetic subjects with normal serum 25‐hydroxyvitamin D levels. Eur J Nutr 2009;48:349‐354.
    1. Mitri J, Dawson‐Hughes B, Hu FB, Pittas AG. Effects of vitamin D and calcium supplementation on pancreatic beta cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CADDM) randomized controlled trial. Am J Clin Nutr 2011;94:486‐494.

Source: PubMed

3
Prenumerera