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      Effect of Vitamin D 3 Supplementation on Serum 25(OH)D, Lipids and Markers of Insulin Resistance in Obese Adolescents: A Prospective, Randomized, Placebo-Controlled Pilot Trial

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          Abstract

          Background/Aims: To determine the effect of vitamin D<sub>3</sub> supplementation on 25-hydroxyvitamin D [25(OH)D], lipid profile and markers of insulin resistance in obese adolescents. Methods: In this double-blind, randomized, placebo-controlled trial, 58 obese adolescents (n = 58; 12-18 years of age) received either vitamin D<sub>3</sub> (2,000 IU/day) or placebo for 12 weeks. Total 25(OH)D, fasting plasma glucose, insulin and lipid profile were measured at baseline and following supplementation. Results: The trial was completed by 44/58 enrolled participants. At the end of the 12 weeks, total serum 25(OH)D concentrations increased to a modest degree (median 6 ng/ml) in the vitamin D-supplemented group (p < 0.001). Supplementation showed no detectable changes in fasting plasma glucose, insulin, homeostatic model of assessment index (HOMA-IR), lipids and highly sensitive C-reactive protein. Conclusions: 12 weeks of vitamin D<sub>3</sub> supplementation in obese adolescents with 2,000 IU once daily resulted in a modest increase in 25(OH)D concentration in obese adolescents, but did not affect the lipid profile and markers of insulin resistance and inflammation. Further studies with higher doses of vitamin D<sub>3</sub> and/or longer duration of supplementation are needed to understand if vitamin D<sub>3</sub> supplementation can impact lipid profiles and markers of insulin resistance and inflammation in obese children.

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          The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis.

          Altered vitamin D and calcium homeostasis may play a role in the development of type 2 diabetes mellitus (type 2 DM). EVIDENCE ACQUISITION AND ANALYSES: MEDLINE review was conducted through January 2007 for observational studies and clinical trials in adults with outcomes related to glucose homeostasis. When data were available to combine, meta-analyses were performed, and summary odds ratios (OR) are presented. Observational studies show a relatively consistent association between low vitamin D status, calcium or dairy intake, and prevalent type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM prevalence, 0.36 (0.16-0.80) among nonblacks for highest vs. lowest 25-hydroxyvitamin D; metabolic syndrome prevalence, 0.71 (0.57-0.89) for highest vs. lowest dairy intake]. There are also inverse associations with incident type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM incidence, 0.82 (0.72-0.93) for highest vs. lowest combined vitamin D and calcium intake; 0.86 (0.79-0.93) for highest vs. lowest dairy intake]. Evidence from trials with vitamin D and/or calcium supplementation suggests that combined vitamin D and calcium supplementation may have a role in the prevention of type 2 DM only in populations at high risk (i.e. glucose intolerance). The available evidence is limited because most observational studies are cross-sectional and did not adjust for important confounders, whereas intervention studies were short in duration, included few subjects, used a variety of formulations of vitamin D and calcium, or did post hoc analyses. Vitamin D and calcium insufficiency may negatively influence glycemia, whereas combined supplementation with both nutrients may be beneficial in optimizing glucose metabolism.
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            Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey.

            To determine the association between serum 25-hydroxyvitamin D (25OHD) and diabetes risk and whether it varies by ethnicity. We performed an analysis of data from participants who attended the morning examination of the Third National Health and Nutrition Examination Survey (1988-1994), a cross-sectional survey of a nationally representative sample of the U.S. population. Serum levels of 25OHD, which reflect vitamin D status, were available from 6,228 people (2,766 non-Hispanic whites, 1,736 non-Hispanic blacks, and 1,726 Mexican Americans) aged > or =20 years with fasting and/or 2-h plasma glucose and serum insulin measurements. Adjusting for sex, age, BMI, leisure activity, and quarter of year, ethnicity-specific odds ratios (ORs) for diabetes (fasting glucose > or =7.0 mmol/l) varied inversely across quartiles of 25OHD in a dose-dependent pattern (OR 0.25 [95% CI 0.11-0.60] for non-Hispanic whites and 0.17 [0.08-0.37] for Mexican Americans) in the highest vitamin D quartile (25OHD > or =81.0 nmol/l) compared with the lowest 25OHD (< or =43.9 nmol/l). This inverse association was not observed in non-Hispanic blacks. Homeostasis model assessment of insulin resistance (log e) was inversely associated with serum 25OHD in Mexican Americans (P=0.0024) and non-Hispanic whites (P=0.058) but not non-Hispanic blacks (P=0.93), adjusting for confounders. These results show an inverse association between vitamin D status and diabetes, possibly involving insulin resistance, in non-Hispanic whites and Mexican Americans. The lack of an inverse association in non-Hispanic blacks may reflect decreased sensitivity to vitamin D and/or related hormones such as the parathyroid hormone.
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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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                Author and article information

                Journal
                HRP
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                1663-2818
                1663-2826
                2014
                August 2014
                16 July 2014
                : 82
                : 2
                : 107-112
                Affiliations
                aDivision of Pediatric Endocrinology, Park Nicollet, St. Louis Park, Minn., Divisions of bLaboratory Medicine and Pathology, cBiomedical Statistics and Informatics and dPediatric Endocrinology and Metabolism, Mayo Clinic, Rochester, Minn., eDivision of Endocrinology, University of Illinois College of Medicine, Peoria, Ill., and fSanford Children's Hospital, Sioux Falls, S. Dak., USA
                Author notes
                *Seema Kumar, Mayo Clinic, 200 First Street SW, Mayo East 16A, Rochester, MN 55905 (USA), E-Mail kumar.seema@mayo.edu
                Article
                362449 Horm Res Paediatr 2014;82:107-112
                10.1159/000362449
                25034315
                4b8b6be7-4fec-4598-a9b8-f8c692dcae9a
                © 2014 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 06 January 2014
                : 19 March 2014
                Page count
                Figures: 2, Tables: 2, Pages: 6
                Categories
                Original Paper

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Insulin resistance,Serum 25(OH)D,Vitamin D3 supplementation,Obese adolescents

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