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      The Role of Vitamin D Oral Supplementation in Insulin Resistance in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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          Abstract

          Objective: To evaluate the effect of vitamin D supplementation (alone or with co-supplementation) on insulin resistance in patients with polycystic ovary syndrome (PCOS). Methods: We performed a literature search of databases (Medline, Scopus, Web of Knowledge, Cochrane Library) and identified all reports of randomized controlled trials (RCTs) published prior to April 2018. We compared the effects of supplementation with vitamin D alone (dose from 1000 IU/d to 60,000 IU/week) or with co-supplements to the administration of placebos in women diagnosed with PCOS. The systematic review and meta-analysis protocol was registered in the International Prospective Register of Systematic Reviews (Prospero) as number CRD42018090572. Main results: Eleven of 345 identified studies were included in the analysis; these involved 601women diagnosed with PCOS. Vitamin D as a co-supplement was found to significantly decrease fasting glucose concentrations and the HOMA-IR value. HOMA-IR also declined significantly when vitamin D was supplemented with a dose lower than 4000 IU/d. Conclusions: Evidence from RCTs suggests that the supplementation of PCOS patients with continuous low doses of vitamin D (<4000 IU/d) or supplementation with vitamin D as a co-supplement may improve insulin sensitivity in terms of the fasting glucose concentration (supplementation with vitamin D in combination with other micronutrients) and HOMA-IR (supplementation with vitamin D in continuous low daily doses or as co-supplement).

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          Insulin resistance (HOMA-IR) cut-off values and the metabolic syndrome in a general adult population: effect of gender and age: EPIRCE cross-sectional study

          Background Insulin resistance has been associated with metabolic and hemodynamic alterations and higher cardio metabolic risk. There is great variability in the threshold homeostasis model assessment of insulin resistance (HOMA-IR) levels to define insulin resistance. The purpose of this study was to describe the influence of age and gender in the estimation of HOMA-IR optimal cut-off values to identify subjects with higher cardio metabolic risk in a general adult population. Methods It included 2459 adults (range 20–92 years, 58.4% women) in a random Spanish population sample. As an accurate indicator of cardio metabolic risk, Metabolic Syndrome (MetS), both by International Diabetes Federation criteria and by Adult Treatment Panel III criteria, were used. The effect of age was analyzed in individuals with and without diabetes mellitus separately. ROC regression methodology was used to evaluate the effect of age on HOMA-IR performance in classifying cardio metabolic risk. Results In Spanish population the threshold value of HOMA-IR drops from 3.46 using 90th percentile criteria to 2.05 taking into account of MetS components. In non-diabetic women, but no in men, we found a significant non-linear effect of age on the accuracy of HOMA-IR. In non-diabetic men, the cut-off values were 1.85. All values are between 70th-75th percentiles of HOMA-IR levels in adult Spanish population. Conclusions The consideration of the cardio metabolic risk to establish the cut-off points of HOMA-IR, to define insulin resistance instead of using a percentile of the population distribution, would increase its clinical utility in identifying those patients in whom the presence of multiple metabolic risk factors imparts an increased metabolic and cardiovascular risk. The threshold levels must be modified by age in non-diabetic women.
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            Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome.

            The polycystic ovary syndrome is a common cause of infertility. Clomiphene and insulin sensitizers are used alone and in combination to induce ovulation, but it is unknown whether one approach is superior. We randomly assigned 626 infertile women with the polycystic ovary syndrome to receive clomiphene citrate plus placebo, extended-release metformin plus placebo, or a combination of metformin and clomiphene for up to 6 months. Medication was discontinued when pregnancy was confirmed, and subjects were followed until delivery. The live-birth rate was 22.5% (47 of 209 subjects) in the clomiphene group, 7.2% (15 of 208) in the metformin group, and 26.8% (56 of 209) in the combination-therapy group (P<0.001 for metformin vs. both clomiphene and combination therapy; P=0.31 for clomiphene vs. combination therapy). Among pregnancies, the rate of multiple pregnancy was 6.0% in the clomiphene group, 0% in the metformin group, and 3.1% in the combination-therapy group. The rates of first-trimester pregnancy loss did not differ significantly among the groups. However, the conception rate among subjects who ovulated was significantly lower in the metformin group (21.7%) than in either the clomiphene group (39.5%, P=0.002) or the combination-therapy group (46.0%, P<0.001). With the exception of pregnancy complications, adverse-event rates were similar in all groups, though gastrointestinal side effects were more frequent, and vasomotor and ovulatory symptoms less frequent, in the metformin group than in the clomiphene group. Clomiphene is superior to metformin in achieving live birth in infertile women with the polycystic ovary syndrome, although multiple birth is a complication. (ClinicalTrials.gov number, NCT00068861 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.
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              Evaluation of the Cochrane tool for assessing risk of bias in randomized clinical trials: overview of published comments and analysis of user practice in Cochrane and non-Cochrane reviews

              Background The Cochrane risk of bias tool for randomized clinical trials was introduced in 2008 and has frequently been commented on and used in systematic reviews. We wanted to evaluate the tool by reviewing published comments on its strengths and challenges and by describing and analysing how the tool is applied to both Cochrane and non-Cochrane systematic reviews. Methods A review of published comments (searches in PubMed, The Cochrane Methodology Register and Google Scholar) and an observational study (100 Cochrane and 100 non-Cochrane reviews from 2014). Results Our review included 68 comments, 15 of which were categorised as major. The main strengths of the tool were considered to be its aim (to assess trial conduct and not reporting), its developmental basis (wide consultation, empirical and theoretical evidence) and its transparent procedures. The challenges of the tool were mainly considered to be its choice of core bias domains (e.g. not involving funding/conflicts of interest) and issues to do with implementation (i.e. modest inter-rater agreement) and terminology. Our observational study found that the tool was used in all Cochrane reviews (100/100) and was the preferred tool in non-Cochrane reviews (31/100). Both types of reviews frequently implemented the tool in non-recommended ways. Most Cochrane reviews planned to use risk of bias assessments as basis for sensitivity analyses (70 %), but only a minority conducted such analyses (19 %) because, in many cases, few trials were assessed as having “low” risk of bias for all standard domains (6 %). The judgement of at least one risk of bias domain as “unclear” was found in 89 % of included randomized clinical trials (1103/1242). Conclusions The Cochrane tool has become the standard approach to assess risk of bias in randomized clinical trials but is frequently implemented in a non-recommended way. Based on published comments and how it is applied in practice in systematic reviews, the tool may be further improved by a revised structure and more focused guidance. Electronic supplementary material The online version of this article (doi:10.1186/s13643-016-0259-8) contains supplementary material, which is available to authorized users.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                02 November 2018
                November 2018
                : 10
                : 11
                : 1637
                Affiliations
                [1 ]Institute ofHuman Nutrition and Dietetics, Poznań University of Life Sciences, Wojska Polskiego 31, 60-624 Poznań, Poland; joanna.bajerska@ 123456up.poznan.pl
                [2 ]Department of Pediatric Gastroenterology and Metabolic Diseases, Poznań University of Medical Sciences, Szpitalna 27/33, 60-572 Poznań, Poland; m_jamka@ 123456wp.pl
                Author notes
                [* ]Correspondence: karolina.lagowska@ 123456up.poznan.pl ; Tel.: +48 61 8487338
                Author information
                https://orcid.org/0000-0003-1996-5198
                Article
                nutrients-10-01637
                10.3390/nu10111637
                6266903
                30400199
                3a16164a-4abd-451c-b078-7728c2abc252
                © 2018 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
                : 05 September 2018
                : 22 October 2018
                Categories
                Review

                Nutrition & Dietetics
                vitamin d,25(oh)d,insulin resistant,glucose,polycystic ovary syndrome
                Nutrition & Dietetics
                vitamin d, 25(oh)d, insulin resistant, glucose, polycystic ovary syndrome

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