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

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          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/m 2 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.

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          Most cited references24

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          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.

          Low serum 25-hydroxyvitamin D (25(OH)D) has been shown to correlate with increased risk of type 2 diabetes. Small, observational studies suggest an action for vitamin D in improving insulin sensitivity and/or insulin secretion. The objective of the present study was to investigate the effect of improved vitamin D status on insulin resistance (IR), utilising randomised, controlled, double-blind intervention administering 100 microg (4000 IU) vitamin D(3) (n 42) or placebo (n 39) daily for 6 months to South Asian women, aged 23-68 years, living in Auckland, New Zealand. Subjects were insulin resistant - homeostasis model assessment 1 (HOMA1)>1.93 and had serum 25(OH)D concentration 25 microg (1000 IU)/d. The HOMA2 computer model was used to calculate outcomes. Median (25th, 75th percentiles) serum 25(OH)D(3) increased significantly from 21 (11, 40) to 75 (55, 84) nmol/l with supplementation. Significant improvements were seen in insulin sensitivity and IR (P = 0.003 and 0.02, respectively), and fasting insulin decreased (P = 0.02) with supplementation compared with placebo. There was no change in C-peptide with supplementation. IR was most improved when endpoint serum 25(OH)D reached > or = 80 nmol/l. Secondary outcome variables (lipid profile and high sensitivity C-reactive protein) were not affected by supplementation. In conclusion, improving vitamin D status in insulin resistant women resulted in improved IR and sensitivity, but no change in insulin secretion. Optimal vitamin D concentrations for reducing IR were shown to be 80-119 nmol/l, providing further evidence for an increase in the recommended adequate levels. Registered Trial No. ACTRN12607000642482.
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            Baseline Serum 25-Hydroxy Vitamin D Is Predictive of Future Glycemic Status and Insulin Resistance

            OBJECTIVE—Accumulating epidemiological evidence suggests that hypovitaminosis D may be associated with type 2 diabetes and related metabolic risks. However, prospective data using the biomarker serum 25-hydroxyvitamin D [25(OH)D] are limited and therefore examined in the present study. RESEARCH DESIGN AND METHODS—A total of 524 randomly selected nondiabetic men and women, aged 40–69 years at baseline, with measurements for serum 25(OH)D and IGF-1 in the population-based Ely Study, had glycemic status (oral glucose tolerance), lipids, insulin, anthropometry, and blood pressure measured and metabolic syndrome risk (metabolic syndrome z score) derived at baseline and at 10 years of follow-up. RESULTS—Age-adjusted baseline mean serum 25(OH)D was greater in men (64.5 nmol/l [95% CI 61.2–67.9]) than women (57.2 nmol/l [54.4,60.0]) and varied with season (highest late summer). Baseline 25(OH)D was associated inversely with 10-year risk of hyperglycemia (fasting glucose: β = −0.0023, P = 0.019; 2-h glucose: β = −0.0097, P = 0.006), insulin resistance (fasting insulin β = −0.1467, P = 0.010; homeostasis model assessment of insulin resistance [HOMA-IR]: β = −0.0059, P = 0.005), and metabolic syndrome z score (β = −0.0016, P = 0.048) after adjustment for age, sex, smoking, BMI, season, and baseline value of each metabolic outcome variable. Associations with 2-h glucose, insulin, and HOMA-IR remained significant after further adjustment for IGF-1, parathyroid hormone, calcium, physical activity, and social class. CONCLUSIONS—This prospective study reports inverse associations between baseline serum 25(OH)D and future glycemia and insulin resistance. These associations are potentially important in understanding the etiology of abnormal glucose metabolism and warrant investigation in larger, specifically designed prospective studies and randomized controlled trials of supplementation.
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              Effects of vitamin D and calcium supplementation on pancreatic β 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.

              A suboptimal vitamin D and calcium status has been associated with higher risk of type 2 diabetes in observational studies, but evidence from trials is lacking. We determined whether vitamin D supplementation, with or without calcium, improved glucose homeostasis in adults at high risk of diabetes. Ninety-two adults were randomly assigned in a 2-by-2 factorial-design, double-masked, placebo-controlled trial to receive either cholecalciferol (2000 IU once daily) or calcium carbonate (400 mg twice daily) for 16 wk. The primary outcome was the change in pancreatic β cell function as measured by the disposition index after an intravenous-glucose-tolerance test. Other outcomes were acute insulin response, insulin sensitivity, and measures of glycemia. Participants had a mean age of 57 y, a body mass index (BMI; in kg/m(2)) of 32, and glycated hemoglobin (Hb A(1c)) of 5.9%. There was no significant vitamin D × calcium interaction on any outcomes. The disposition index increased in the vitamin D group and decreased in the no-vitamin D group (adjusted mean change ± SE: 300 ± 130 compared with -126 ± 127, respectively; P = 0.011), which was explained by an improvement in insulin secretion (62 ± 39 compared with -36 ± 37 mU · L(-1) · min, respectively; P = 0.046). Hb A(1c) increased less, but nonsignificantly, in the vitamin D group than in the no-vitamin D group (0.06 ± 0.03% compared with 0.14 ± 0.03%, respectively; P = 0.081). There was no significant difference in any outcomes with calcium compared with no calcium. In adults at risk of type 2 diabetes, short-term supplementation with cholecalciferol improved β cell function and had a marginal effect on attenuating the rise in Hb A(1c). This trial was registered at clinicaltrials.gov as NCT00436475.
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                Author and article information

                Contributors
                teresa.mezza@gmail.com
                Journal
                Obesity (Silver Spring)
                Obesity (Silver Spring)
                10.1002/(ISSN)1930-739X
                OBY
                Obesity (Silver Spring, Md.)
                John Wiley and Sons Inc. (Hoboken )
                1930-7381
                1930-739X
                04 March 2018
                April 2018
                : 26
                : 4 ( doiID: 10.1002/oby.v26.4 )
                : 651-657
                Affiliations
                [ 1 ] Center for Endocrine and Metabolic Diseases, Gemelli University Polyclinic Foundation, Catholic University of the Sacred Heart Rome Italy
                [ 2 ] Internal Medicine and Transplant Unit, San Raffaele Hospital Milan Italy
                [ 3 ] Center for Diabetes and Metabolic Diseases, Association of Italian Knights of the Sovereign Military Order of Malta Rome Italy
                [ 4 ] Division of Endocrinology, Department of Clinical Medicine and Surgery Federic II University Naples Italy
                Author notes
                [*] [* ]Correspondence: Teresa Mezza ( teresa.mezza@ 123456gmail.com )

                Funding agencies: This study was supported by grants from the Catholic University of the Sacred Heart (Fondi Ateneo Linea D.3.2); the Italian Ministry of Education, University and Research (PRIN 2015373Z39_006); a European Foundation for the Study of Diabetes award supported by Astra Zeneca (to AG); and European Foundation for the Study of Diabetes Novo Nordisk, Lilly, and Astra Zeneca Awards (to TM). CC and GPS are recipients of a fellowship from Fondazione Roma, and CMAC is the recipient of a fellowship prize from Diabete Ricerca.

                Author information
                http://orcid.org/0000-0001-5407-9576
                Article
                OBY22132
                10.1002/oby.22132
                6175391
                29504254
                7fac3421-862e-4caf-9b6f-e02336517c7a
                © 2018 The Authors. Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS)

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 04 October 2017
                : 27 December 2017
                : 29 December 2017
                Page count
                Figures: 3, Tables: 2, Pages: 7, Words: 4280
                Funding
                Funded by: Catholic University of the Sacred Heart
                Funded by: Rome Foundation (Grant for Biomedical Research)
                Funded by: CMAC
                Award ID: 2014/2015
                Funded by: Italian Society of Diabetology
                Funded by: European Association for the Study of Diabetes
                Funded by: Fondi Ateneo
                Award ID: Linea D.1 2015
                Award ID: Linea D.1 2016
                Award ID: Linea D.2.3 2015
                Award ID: Linea D.3.2 Sindrome Metabolica
                Funded by: società italiana di diabetologia
                Award ID: FODIRI‐MSD 2014/2015
                Categories
                Original Article
                Original Articles
                Clinical Trials and Investigations
                Custom metadata
                2.0
                oby22132
                April 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.5.0 mode:remove_FC converted:08.10.2018

                Medicine
                Medicine

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