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      Vitamin D Status, Calcium Intake and Risk of Developing Type 2 Diabetes: An Unresolved Issue

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          Abstract

          The relationship between vitamin D status, calcium intake and the risk of developing type 2 diabetes (T2D) is a topic of growing interest. One of the most interesting non-skeletal functions of vitamin D is its potential role in glucose homeostasis. This possible association is related to the secretion of insulin by pancreatic beta cells, insulin resistance in different tissues and its influence on systemic inflammation. However, despite multiple observational studies and several meta-analyses that have shown a positive association between circulating 25-hydroxyvitamin D concentrations and the risk of T2D, no randomized clinical trials supplementing with different doses of vitamin D have confirmed this hypothesis definitively. An important question is the identification of what 25-hydroxyvitamin D levels are necessary to influence glycemic homeostasis and the risk of developing T2D. These values of vitamin D can be significantly higher than vitamin D levels required for bone health, but the currently available data do not allow us to answer this question adequately. Furthermore, a large number of observational studies show that dairy consumption is linked to a lower risk of T2D, but the components responsible for this relationship are not well established. Therefore, the importance of calcium intake in the risk of developing T2D has not yet been established. Although there is a biological plausibility linking the status of vitamin D and calcium intake with the risk of T2D, well-designed randomized clinical trials are necessary to answer this important question.

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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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            IOM committee members respond to Endocrine Society vitamin D guideline.

            In early 2011, a committee convened by the Institute of Medicine issued a report on the Dietary Reference Intakes for calcium and vitamin D. The Endocrine Society Task Force in July 2011 published a guideline for the evaluation, treatment, and prevention of vitamin D deficiency. Although these reports are intended for different purposes, the disagreements concerning the nature of the available data and the resulting conclusions have caused confusion for clinicians, researchers, and the public. In this commentary, members of the Institute of Medicine committee respond to aspects of The Endocrine Society guideline that are not well supported and in need of reconsideration. These concerns focus on target serum 25-hydroxyvitamin D levels, the definition of vitamin D deficiency, and the question of who constitutes a population at risk vs. the general population.
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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
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                16 March 2019
                March 2019
                : 11
                : 3
                : 642
                Affiliations
                [1 ]Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA), 29010 Malaga, Spain
                [2 ]Instituto de Salud Carlos III, 28029 Madrid, Spain
                [3 ]Instituto de Investigación Biosanitaria (Ibs.GRANADA), 18106 Granada, Spain; bgfontana@ 123456fibao.es
                [4 ]Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain
                [5 ]Unidad de Gestión Clínica Endocrinología y Nutrición, Hospital Universitario San Cecilio de Granada, Avenida de la Innovacion, 18016 Granada, Spain
                [6 ]Department of Medicine, University of Granada, 18016 Granada, Spain
                Author notes
                [* ]Correspondence: aracelimugar@ 123456gmail.com (A.M.-G.); mmt@ 123456mamuto.es (M.M.-T.); Tel.: +34-646032764 (A.M.-G.); +34-678481018 (M.M.-T.)
                Author information
                https://orcid.org/0000-0002-1867-1158
                https://orcid.org/0000-0002-9645-3260
                Article
                nutrients-11-00642
                10.3390/nu11030642
                6471926
                30884820
                09ddda1a-8db8-48f2-92a5-c60934c647f4
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 27 February 2019
                : 12 March 2019
                Categories
                Communication

                Nutrition & Dietetics
                calcium intake,dairy products,vitamin d,type 2 diabetes
                Nutrition & Dietetics
                calcium intake, dairy products, vitamin d, type 2 diabetes

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