Effect of vitamin D supplementation on inflammation: protocol for a systematic review Efficacy of vitamin D supplementation in depression in adults: a systematic review protocol A systematic review protocol examining the effect of vitamin D supplementation on endothelial function Effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes: a systematic review of interventional studies The Effectiveness of Psychosocial Interventions as Adjuncts to Orthopaedic Surgery: A Systematic Review Protocol Role of Vitamin D in Insulin Secretion and Insulin Sensitivity for Glucose Homeostasis A double-blind, randomized, placebo-controlled trial of the short-term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men. Vitamin D supplementation has no effect on insulin sensitivity or secretion in vitamin D-deficient, overweight or obese adults: a randomized placebo-controlled trial. Maternal vitamin D supplementation during pregnancy Effects of Combined Calcium and Vitamin D Supplementation on Insulin Secretion, Insulin Sensitivity and β-Cell Function in Multi-Ethnic Vitamin D-Deficient Adults at Risk for Type 2 Diabetes: A Pilot Randomized, Placebo-Controlled Trial Addressing Dichotomous Data for Participants Excluded from Trial Analysis: A Guide for Systematic Reviewers High-Dose Vitamin D Supplementation in People With Prediabetes and Hypovitaminosis D Vitamin D, Insulin Secretion, Sensitivity, and Lipids Vitamin D supplementation has no effect on insulin resistance assessment in women with polycystic ovary syndrome and vitamin D deficiency. Effect of Vitamin D Supplementation on Obesity‐Induced Insulin Resistance: A Double‐Blind, Randomized, Placebo‐Controlled Trial Effect of moderate-dose vitamin D supplementation on insulin sensitivity in vitamin D-deficient non-Western immigrants in the Netherlands: a randomized placebo-controlled trial. 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. A randomized, placebo-controlled trial of vitamin D supplementation to improve glycaemia in overweight and obese African Americans. Vitamin D supplementation for the prevention of type 2 diabetes in overweight adults: study protocol for a randomized controlled trial The impact of outcome reporting bias in randomised controlled trials on a cohort of systematic reviews Effect of long-term nutraceutical and dietary supplement use on cognition in the elderly: a 10-year systematic review of randomised controlled trials. Comparative Effectiveness of Dipeptidylpeptidase-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison Sources of evidence for systematic reviews of interventions in diabetes.
Introduction The extraskeletal role of vitamin D is being increasingly recognised . This has important clinical implication s , as vitamin D deficiency has reached epidemic proportions worldwide . Vitamin D has proposed anti-inflammatory properties , yet the role of vitamin D supplementation in reducing inflammation remains largely unknown . The purpose of this review is to investigate the impact of vitamin D supplementation on inflammation , and to identify relevant knowledge gaps in the field . Methods and analysis Medline , CINAHL , EMBASE and All EBM will be systematic ally search ed for r and omised controlled trials ( RCTs ) and systematic review s of RCTs , comparing vitamin D supplementation with placebo , usual care or other pharmacological or non-pharmacological interventions . One review er will assess articles for eligibility according to prespecified selection criteria , after which 2 independent review ers will perform data extraction and quality appraisal . Meta-analyses will be conducted where appropriate . Ethics and dissemination Formal ethical approval is not required as no primary data is collected . This systematic review will identify potential clinical implication s of vitamin D deficiency and supplementation , and will be disseminated through a peer- review ed publication and at conference meetings , to inform future research on the efficacy of vitamin D supplementation for inflammation and inflammatory diseases . PROSPERO registration number CRD42016037104 Background The role of vitamin D in management of depression is unclear . Results from observational and emerging r and omized controlled trials ( RCTs ) investigating the efficacy of vitamin D in depression lack consistency - with some suggesting a positive association while others show a negative or inconclusive association . Methods / Design The primary aim of this study is to conduct a systematic review of RCTs to assess the effect of oral vitamin D supplementation versus placebo on depression symptoms measured by scales and the proportion of patients with symptomatic improvement according to the authors ’ original definition . Secondary aims include assessing the change in quality of life , adverse events and treatment discontinuation . We will conduct the systematic review and meta- analysis according to the recommendations of the Cochrane H and book for Systematic Review s of Interventions . We will search the Cochrane Central Register of Controlled Trials ( CENTRAL ) , MEDLINE ( 1966 to present ) , EMBASE ( 1980 to present ) , CINAHL ( 1982 to present ) , PsychINFO ( 1967 to present ) and Clinical Trials.gov . Unpublished work will be identified by search ing two major conferences : the International Vitamin Conference , the Anxiety Disorders and Depression Conference , while grey literature will be acquired by contacting authors of included studies . We will use the r and om-effects meta- analysis to synthesize the data by pooling the results of included studies . Discussion The results of this systematic review will be helpful in clarifying the efficacy of vitamin D supplementation and providing evidence to establish guidelines for implementation of vitamin D for depression in general practice and other relevant setting s. Study registration Unique identifier : CRD42013003849 Introduction Vitamin D has potential benefits for extraskeletal health . These could include an anti-inflammatory effect as well as a reduction in endothelial dysfunction . We aim to provide quality evidence for the hypothesis that supplementation with vitamin D will improve endothelial function ( EF ) , possibly through the abrogation of systemic inflammation . Methods and analysis We will conduct a systematic review of all r and omised controlled trials on  vitamin D supplementation and EF lasting 12 weeks or more . The search will cover the period 2000–2015 and include studies that describe direct measures of EF  , markers of endothelial cell ( EC ) activation  and if concurrently reported , indicators of systemic inflammation  . Study selection will follow the Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines and study quality will be assessed by the Jadad score in addition to an evaluation of allocation concealment and data analysis . If sufficient data are available , a meta- analysis will be conducted . The effect sizes will be generated using Hedges ’ g score , for both fixed and r and om effect models . I2 statistics and Galbraith plots will be used to assess heterogeneity and identify their potential sources . Potential publication and small sample size bias will be assessed by visual inspections of funnel plots and also Egger 's test . Meta-regression analysis ( if feasible ) will be conducted with restricted maximum likelihood ( REML ) estimation method , controlling for potential confounders ( demographics , study methods , location , etc ) . A backward elimination process will be applied in the regression modelling procedure . Subgroup analysis , conditional on number of studies retrieved and their sample size , will be stratified on participant disease category , total dose administered , degree of 25(OH)D change and type of supplement used . Ethics and dissemination Formal ethical approval is not required as primary data will not be collected . The results will be disseminated through a peer- review ed publication , conference presentation and the popular press . Trial registration number International Prospect i ve Register for Systematic Review s ( PROSPERO ) number CRD42014013523 Background Diabetes and vitamin D deficiency are global epidemics . Research ers have long been exploring the role of potentially modifiable factors to manage type 2 diabetes . We conducted a systematic review of prospect i ve studies and r and omized controlled trials that involved vitamin D supplementation and specifically intended to study glycemic outcomes related to type 2 diabetes . Methods Two authors independently search ed Medline and PubMed for longitudinal studies that had assessed the effect of vitamin D supplements on glycemic control , insulin resistance and beta-cell dysfunction in patients with diabetes . Results Seventeen r and omized control trials and seven longitudinal studies with a minimum follow-up of one month were included . Results of the various short-term studies ( follow up ≤ 3 months ) suggested that vitamin D supplementation had a positive impact on glycemic control and metabolic parameters such as insulin resistance and beta cell dysfunction . However , the evidence was weak due to the low method ological quality of the studies . There was no significant effect on HbA1c , beta cell function and insulin resistance in the long-term studies ( follow up > 3 months ) . There existed heterogeneity in the methodology of the studies , inclusion criteria , mode of supplementation of vitamin D and the duration of follow up . Conclusions Current evidence based on r and omized controlled trials and longitudinal studies do not support the notion that vitamin D supplementation can improve hyperglycemia , beta cell secretion or insulin sensitivity in patients with type 2 diabetes . Large-scale trials with proper study design , optimal vitamin D supplementation and longer follow up need to be conducted AIMS Pain and anxiety are commonly reported among those undergoing orthopaedic surgery . Improvement in anxiety and pain control might be achieved by supplementing st and ard care with psychological interventions . However , the effectiveness of adjunctive psychosocial interventions in anxiety and pain control have not been addressed sufficiently by previous systematic review s in orthopaedic surgeries . The present study aim ed to assess the effectiveness of adjunctive psychosocial techniques to improve perioperative clinical care in orthopaedic surgery , to identify the most effective intervention types and to evaluate potential moderators . METHODS We will perform a systematic review and meta- analysis to address the study aims . PubMed , PsycINFO , CINAHL and ProQuest Dissertations & Theses will be search ed between 1980 and 2015 . Prospect i ve controlled clinical trials completed in adults , contrasting st and ard care and st and ard care supplemented with psychosocial methods  , will be eligible for inclusion . Effectiveness will be assessed through the outcomes of postoperative pain intensity , analgesic requirement , perioperative anxiety , quality of life and postoperative recovery . The results of a r and om-effect meta- analysis will be reported . To aid implementation of best practice , moderating effects of the type and timing of psychosocial intervention , type of surgical intervention and type of anaesthesia will be evaluated through meta-regression . Sensitivity analyses and subgroup contrasts will follow as necessary . DISCUSSION Recommendations will be made to improve medical care in orthopaedic procedures . The quality of evidence will be rated using GRADE criteria . Copyright © 2016 John Wiley & Sons , Vitamin D functions are not limited to skeletal health benefits and may extend to preservation of insulin secretion and insulin sensitivity . This review summarizes the literature related to potential vitamin D influences on glucose homeostasis and insulin sensitivity . Cross-sectional data provide some evidence that circulating 25-hydroxyvitamin D ( 25(OH)D ) is inversely associated with insulin resistance , although direct measurements of insulin sensitivity are required for confirmation . Reported associations with insulin secretion , however , are contradictory . Available prospect i ve studies support a protective influence of high 25(OH)D concentrations on type 2 diabetes mellitus risk . There is a general lack of consistency in vitamin D intervention outcomes on insulin secretion and sensitivity , likely due to differences in subject population s , length of interventions , and forms of vitamin D supplementation . Vitamin D receptor gene polymorphisms and vitamin D interactions with the insulin like growth factor system may further influence glucose homeostasis . The ambiguity of optimal vitamin D dosing regimens and optimal therapeutic concentrations of serum 25(OH)D limit available intervention studies . Future studies , including cross-sectional and prospect i ve , should be performed in population s at high risk for both vitamin D deficiency and type 2 diabetes mellitus . Well- design ed , placebo-controlled , r and omized intervention studies are required to establish a true protective influence of  vitamin D on glucose homeostasis AIM To determine the short-term effect of vitamin D(3 ) supplementation on insulin sensitivity in apparently healthy , middle-aged , central ly obese men . SUBJECTS AND METHODS A double-blind r and omized controlled trial was conducted at a tertiary care facility in which 100 male volunteers aged > or = 35 years received three doses of vitamin D(3 ) ( 120,000 IU each ; supplemented group ) fortnightly or placebo ( control group ) . Hepatic fasting insulin sensitivity [ homeostasis model assessment ( HOMA ) , quantitative insulin-sensitivity check index , HOMA-2 ] , postpr and ial insulin sensitivity [ oral glucose insulin sensitivity ( OGIS ) ] , insulin secretion ( HOMA%B , HOMA2-%B ) , lipid profile and blood pressure were measured at baseline and at 6 weeks ' follow-up . RESULTS Seventy-one of the recruited subjects completed the study ( 35 in supplemented group , 36 in control group ) . There was an increase in OGIS with supplementation by per protocol analysis ( P = 0.038 ; intention-to-treat analysis P = 0.055 ) . The age- and baseline 25-hydroxyvitamin D level-adjusted difference in change in OGIS was highly significant ( mean difference 41.1 + /- 15.5 ; P = 0.01 ) . No changes in secondary outcome measures ( insulin secretion , basal indices of insulin sensitivity , blood pressure or lipid profile ) were found with supplementation . CONCLUSION The trial indicates that vitamin D(3 ) supplementation improves postpr and ial insulin sensitivity ( OGIS ) in apparently healthy men likely to have insulin resistance ( central ly obese but non-diabetic ) Background : Vitamin D supplementation has been proposed as a potential strategy to prevent  type 2 diabetes .  Existing clinical trials have been limited by short duration , low doses of vitamin D , variability in participants ' vitamin D-deficiency status , and the use of surrogate measures of body composition , insulin sensitivity , and insulin secretion . Objective : To address existing knowledge gaps , we conducted a double-blind , r and omized , placebo-controlled trial to investigate whether vitamin D supplementation that is provided in a sufficient dose and duration to vitamin D-deficient individuals would improve insulin sensitivity or secretion as measured with the use of gold-st and ard methods . We hypothesized that vitamin D supplementation would improve insulin sensitivity and secretion compared with placebo . Design : Sixty-five overweight or obese , vitamin D-deficient ( 25-hydroxyvitamin D [ 25(OH)D ] concentration ≤50 nmol/L ) adults were r and omly assigned to receive either a bolus oral dose of 100,000 IU cholecalciferol followed by 4000 IU cholecalciferol/d or a matching placebo for 16 wk . Before and after the intervention , participants received gold-st and ard assessment s of body composition ( via dual X-ray absorptiometry ) , insulin sensitivity ( via hyperinsulinemic-euglycemic clamps ) , and insulin secretion [ via intravenous-glucose-tolerance tests ( IVGTTs ) ] . Results : Fifty-four participants completed the study [ 35 men and 19 women ; mean ± SD age : 31.9 ± 8.5 y ; body mass index ( in kg/m2 ) : 30.9 ± 4.4 ] . 25(OH)D increased with vitamin D supplementation compared with placebo ( 57.0 ± 21.3 compared with 1.9 ± 15.1 nmol/L , respectively ; P = 0.02 ) . Vitamin D and placebo groups did not differ in change in insulin sensitivity ( 0.02 ± 2.0 compared with -0.03 ± 2.8 mg · kg-1 · min-1 , respectively ; P = 0.9 ) or first-phase insulin secretion ( -21 ± 212 compared with 24 ± 184 mU/L , respectively ; P = 0.9 ) . Results remained nonsignificant after adjustment for age , sex , percentage of body fat , sun exposure , physical activity , and dietary vitamin D intake ( P > 0.1 ) . Conclusions : Vitamin D supplementation does not improve insulin sensitivity or secretion in vitamin D-deficient , overweight or obese adults , despite using high-dose vitamin D supplementation and robust endpoint measures . Therefore , it is unlikely that vitamin D supplementation would be an effective strategy for reducing diabetes risk even in vitamin D-deficient population s. This trial was registered at clinical trials.gov as NCT02112721 Introduction Maternal vitamin D status in pregnancy has been linked to many health outcomes in mother and offspring . A wealth of observational studies have reported on both obstetric outcomes and complications , including pre-eclampsia , gestational diabetes , mode and timing of delivery . Many foetal and childhood outcomes are also linked to vitamin D status , including measures of foetal size , body composition and skeletal mineralization , in addition to later childhood outcomes , such as asthma . Sources of data Synthesis of systematic and narrative review s. Areas of agreement and controversy The findings are generally inconsistent in most areas , and , at present , there is a lack of data from high- quality intervention studies to confirm a causal role for vitamin D in these outcomes . In most areas , the evidence tends towards maternal vitamin D being of overall benefit , but often does not reach statistical significance in meta-analyses . Growing points and areas timely for developing research The most conclusive evidence is in the role of maternal vitamin D supplementation in the prevention of neonatal hypocalcaemia ; as a consequence the UK department of health recommends that pregnant women take 400 IU vitamin D daily . High- quality r and omized placebo-controlled trials , such as the UK-based MAVIDOS trial , will inform the potential efficacy and safety of vitamin D supplementation in pregnancy across a variety of outcomes Objectives To examine whether combined vitamin D and calcium supplementation improves insulin sensitivity , insulin secretion , β-cell function , inflammation and metabolic markers . Design 6-month r and omized , placebo-controlled trial . Participants Ninety-five adults with serum 25-hydroxyvitamin D [ 25(OH)D ] ≤55 nmol/L at risk of type 2 diabetes ( with prediabetes or an AUSDRISK score ≥15 ) were r and omized . Analyses included participants who completed the baseline and final visits ( treatment n = 35 ; placebo n = 45 ) . Intervention Daily calcium carbonate ( 1,200 mg ) and cholecalciferol [ 2,000–6,000 IU to target 25(OH)D > 75 nmol/L ] or matching placebos for 6 months .  Measurements Insulin sensitivity ( HOMA2%S , Matsuda index ) , insulin secretion ( insulinogenic index , area under the curve ( AUC ) for C-peptide ) and β-cell function ( Matsuda index x AUC for C-peptide ) derived from a 75 g 2-h OGTT ; anthropometry ; blood pressure ; lipid profile ; hs-CRP ; TNF-α ; IL-6 ; adiponectin ; total and undercarboxylated osteocalcin . Results Participants were middle-aged adults ( mean age 54 years ; 69 % Europid ) at risk of type 2 diabetes ( 48 % with prediabetes ) . Compliance was > 80 % for calcium and vitamin D. Mean serum 25(OH)D concentration increased from 48 to 95 nmol/L in the treatment group ( 91 % achieved > 75 nmol/L ) , but remained unchanged in controls . There were no significant changes in insulin sensitivity , insulin secretion and β-cell function , or in inflammatory and metabolic markers between or within the groups , before or after adjustment for potential confounders including waist circumference and season of recruitment . In a post hoc analysis restricted to participants with prediabetes , a significant beneficial effect of vitamin D and calcium supplementation on insulin sensitivity ( HOMA%S and Matsuda ) was observed . Conclusions Daily vitamin D and calcium supplementation for 6 months may not change OGTT-derived measures of insulin sensitivity , insulin secretion and β-cell function in multi-ethnic adults with low vitamin D status at risk of type 2 diabetes . However , in participants with prediabetes , supplementation with vitamin D and calcium may improve insulin sensitivity . Trial Registration Australian New Zeal and Clinical Trials Registry Introduction Systematic review er authors intending to include all r and omized participants in their meta-analyses need to make assumptions about the outcomes of participants with missing data . Objective The objective of this paper is to provide systematic review er authors with a relatively simple guidance for addressing dichotomous data for participants excluded from analyses of r and omized trials . Methods This guide is based on a review of the Cochrane h and book and published method ological research . The guide deals with participants excluded from the analysis who were considered ‘ non-adherent to the protocol ’ but for whom data are available , and participants with missing data . Results Systematic review er authors should include data from ‘ non-adherent ’ participants excluded from the primary study authors ' analysis but for whom data are available . For missing , unavailable participant data , authors may conduct a complete case analysis ( excluding those with missing data ) as the primary analysis . Alternatively , they may conduct a primary analysis that makes plausible assumptions about the outcomes of participants with missing data . When the primary analysis suggests important benefit , sensitivity meta-analyses using relatively extreme assumptions that may vary in plausibility can inform the extent to which risk of bias impacts the confidence in the results of the primary analysis . The more plausible assumptions draw on the outcome event rates within the trial or in all trials included in the meta- analysis . The proposed guide does not take into account the uncertainty associated with assumed events . Conclusions This guide proposes methods for h and ling participants excluded from analyses of r and omized trials . These methods can help in establishing the extent to which risk of bias impacts meta- analysis results OBJECTIVE Low vitamin D levels predict the development of diabetes . This double-blind , r and omized , control study in subjects with prediabetes and hypovitaminosis D evaluated whether high doses of vitamin D for 1 year affected insulin secretion , insulin sensitivity , and the development of diabetes . RESEARCH DESIGN AND METHODS A total of 1,551 subjects ≥40 years of age not known to have diabetes were screened with A1C levels . Subjects with A1C levels of 5.8–6.9 % underwent an oral glucose tolerance test ( OGTT ) . Subjects with prediabetes and 25-OH vitamin D ( 25-OHD ) levels < 30 ng/mL were r and omized to receive weekly placebo ( n = 53 ) or vitamin D ( n = 56 ) with doses based on body weight and baseline 25-OHD levels . OGTTs were performed 3 , 6 , 9 , and 12 months later . Insulin secretion and sensitivity were measured , and the proportion of subjects developing diabetes was assessed . RESULTS 25-OHD levels rapidly rose from 22 to nearly 70 ng/mL after vitamin D supplementation with a mean weekly dose of 88,865 IU . There were no differences between the placebo and vitamin D groups regarding fasting plasma glucose , 2-h glucose , or insulin secretion and sensitivity or in the percent developing diabetes or returning to normal glucose tolerance . No subjects experienced increased serum or urinary calcium levels . At 12 months , A1C levels were significantly slightly less ( 0.2 % ) in the vitamin D group . CONCLUSIONS In individuals with prediabetes and hypovitaminosis D , doses of vitamin D supplementation design ed to raise serum 25-OHD levels into the upper-normal range for 1 year had no effect on insulin secretion , insulin sensitivity , or the development of diabetes  compared with placebo administration OBJECTIVE Vitamin D deficiency is associated with an unfavorable metabolic profile in observational studies . The intention was to compare insulin sensitivity ( the primary end point ) and secretion and lipids in subjects with low and high serum 25(OH)D ( 25-hydroxyvitamin D ) levels and to assess the effect of vitamin D supplementation on the same outcomes among the participants with low serum 25(OH)D levels . RESEARCH DESIGN AND METHODS Participants were recruited from a population -based study ( the Tromsø Study ) based on their serum 25(OH)D measurements . A 3-h hyperglycemic clamp was performed , and the participants with low serum 25(OH)D levels were thereafter r and omized to receive capsules of 20,000 IU vitamin D3 or identical-looking placebo twice weekly for 6 months . A final hyperglycemic clamp was then performed . RESULTS The 52 participants with high serum 25(OH)D levels ( 85.6 ± 13.5 nmol/L [ mean ± SD ] ) had significantly higher insulin sensitivity index ( ISI ) and lower HbA1c and triglycerides ( TGs ) than the 108 participants with low serum 25(OH)D ( 40.3 ± 12.8 nmol/L ) , but the differences in ISI and TGs were not significant after adjustments . After supplementation , serum 25(OH)D was 142.7 ± 25.7 and 42.9 ± 17.3 nmol/L in 49 of 51 completing participants r and omized to vitamin D and 45 of 53 r and omized to placebo , respectively . At the end of the study , there were no statistically significant differences in the outcome variables between the two groups . CONCLUSIONS Vitamin D supplementation to apparently healthy subjects with insufficient serum 25(OH)D levels does not improve insulin sensitivity or secretion or serum lipid profile Insulin resistance is one of the most common features of polycystic ovary syndrome ( PCOS ) . Some studies suggest that vitamin D deficiency may have a role in insulin resistance ; thus , the aim of the current study was to determine the effect of vitamin D supplementation on insulin resistance in women with PCOS and a vitamin D deficiency . We hypothesized that vitamin D supplementation would lower the glucose level and insulin resistance in women with PCOS and a vitamin D deficiency . The current study was a r and omized , placebo-controlled , double-blinded trial with 50 women with PCOS and a vitamin D deficiency , 20 to 40 years old , assigned to receive 3 oral treatments consisting of 50,000 IU of vitamin D₃ or a placebo ( 1 every 20 days ) for 2 months ( vitamin D , n = 24 ; placebo , n = 26 ) . The fasting blood glucose , insulin , 25-hydroxyvitamin D , and parathyroid hormone levels , as well as the homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were measured at baseline and after treatment . In the vitamin D group , the serum level of 25-hydroxyvitamin D increased ( 6.9 ± 2.8 to 23.4 ± 6.1 ng/mL , P < .0001 ) , and the parathyroid hormone level decreased ( 70.02 ± 43.04 to 50.33 ± 21.99 μ IU/mL , P = .02 ) . There were no significant changes in the placebo group . There was a significant increase in insulin secretion in the vitamin D group ( P = .01 ) , but this was not significant compared with the placebo group . The fasting serum insulin and glucose levels and the insulin sensitivity and homeostasis model assessment of insulin resistance did not change significantly by the end of the study . We were not able to demonstrate the effect of vitamin D supplementation on insulin sensitivity and insulin resistance in women with PCOS and vitamin D deficiency 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 r and omized ( 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 BACKGROUND Low serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations have been associated with insulin resistance , the metabolic syndrome , and type 2 diabetes . Because many non-Western immigrants in the Netherl and s are vitamin D deficient , obese , and at high risk of diabetes , vitamin D supplementation may contribute to prevent diabetes and insulin resistance . OBJECTIVE We examined the effect of vitamin D supplementation on insulin sensitivity and β cell function in overweight , vitamin D-deficient , non-Western immigrants at high risk of diabetes . DESIGN The study was a 16-wk , r and omized , placebo-controlled trial . A total of 130 non-Western immigrants with prediabetes ( fasting glucose concentration > 5.5 mmol/L or r and om glucose concentration from 7.8 to 11.1 mmol/L ) and vitamin D deficiency ( serum 25[OH]D concentration < 50 nmol/L ) were r and omly assigned after stratification by sex to receive either cholecalciferol ( 1200 IU/d ) or a placebo for 16 wk . All participants received 500 mg Ca/d as calcium carbonate . The primary outcome was the difference in the area under the curve of insulin and glucose after a 75-g oral-glucose-tolerance test after 4 mo of treatment . Secondary outcomes were insulin-sensitivity variables , β cell-function variables , and metabolic syndrome . RESULTS Mean serum 25(OH)D concentrations increased significantly in the vitamin D compared with placebo groups . After 4 mo of therapy , the mean between-group difference was 38 nmol/L ( 95 % CI : 32.1 , 43.9 nmol/L ; P < 0.001 ) . There was no significant effect on insulin sensitivity and β cell function . In a post hoc analysis , when patients with diabetes at baseline were excluded , a significant increase in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L ( P = 0.040 ) . CONCLUSIONS Vitamin D supplementation in non-Western vitamin D-deficient immigrants with prediabetes did not improve insulin sensitivity or β cell function or change the incidence of metabolic syndrome . However , after the exclusion of diabetic subjects , an improvement in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L. This trial was registered at trialregister.nl as NTR1827 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 r and omised , 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 Auckl and , New Zeal and . Subjects were insulin resistant - homeostasis model assessment 1 (HOMA1)>1.93 and had serum 25(OH)D concentration < 50 nmol/l . Exclusion criteria included diabetes medication and vitamin D supplementation > 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 result ed 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 AIMS Vitamin D deficiency may increase the risk for type 2 diabetes . African Americans tend to have poor vitamin D status and increased risk of diabetes , but effects of vitamin D supplementation on components of diabetes risk have not been tested in this group . This study was conducted to determine whether vitamin D supplementation improves insulin secretion , insulin sensitivity and glycaemia in African Americans with prediabetes or early diabetes . METHODS In this r and omized , placebo-controlled trial , we examined the effect of 4000 IU/day vitamin D(3 , ) on glycaemia and contributing measures including insulin secretion , insulin sensitivity and the disposition index over 12 weeks in 89 overweight or obese African Americans with prediabetes or early diabetes . Outcome measures were derived from oral glucose tolerance testing . RESULTS Mean plasma 25-hydroxyvitamin D was about 40 nmol/l in the placebo and vitamin D groups at baseline and increased to 81 nmol/l with supplementation . Insulin sensitivity decreased by 4 % in the vitamin D group compared with a 12 % increase in the placebo group ( p = 0.034 ) . Insulin secretion increased by 12 % in the vitamin D group compared with a 2 % increase in the placebo group ( p = 0.024 ) , but changes in the disposition index were similar across groups . There was no effect of supplementation on post-load glucose or other measures of glycaemia . CONCLUSIONS Supplementation with 4000 IU/day vitamin D(3 ) successfully corrected vitamin D insufficiency and had divergent effects on insulin secretion and sensitivity with no overall effect on disposition index or glycaemia . In this study , vitamin D supplementation for 3 months did not change the pathophysiology of prediabetes in overweight and obese African Americans Background Despite Australia ’s sunny climate , low vitamin D levels are increasingly prevalent . Sun exposure is limited by long working hours , an increase in time spent indoors , and sun protection practice s , and there is limited dietary vitamin D fortification . While the importance of vitamin D for bone mineralization is well known , its role as a protective agent against chronic diseases , such as type 2 diabetes and cardiovascular disease , is less understood . Observational and limited intervention studies suggest that vitamin D might improve insulin sensitivity and secretion , mainly via its anti-inflammatory properties , thereby decreasing the risk of development and progression of type 2 diabetes . The primary aim of this trial is to investigate whether improved plasma concentrations of 25-hydroxyvitamin D ( 25(OH)D ) , obtained through vitamin D supplementation , will increase insulin sensitivity and insulin secretion . A secondary aim is to determine whether these relationships are mediated by a reduction in underlying sub clinical inflammation associated with obesity . Methods / Design Fifty overweight but otherwise healthy nondiabetic adults between 18 and 60 years old , with low vitamin D levels ( 25(OH)D < 50 nmol/l ) , will be r and omly assigned to intervention or placebo . At baseline , participants will undergo a medical review and anthropometric measurements , including dual X-ray absorptiometry , an intravenous glucose tolerance test , muscle and fat biopsies , a hyperinsulinemic euglycemic clamp  , and question naires assessing diet , physical activity , sun exposure , back and knee pain , and depression . The intervention group will receive a first dose of 100,000 IU followed by 4,000 IU vitamin D ( cholecalciferol ) daily , while the placebo group will receive apparently identical capsules , both for a period of 16 weeks . All measurements will be repeated at follow-up , with the primary outcome measure expressed as a change from baseline in insulin sensitivity and secretion for the intervention group compared with the placebo group . Secondary outcome measures will compare changes in anthropometry , cardiovascular risk factors , and inflammatory markers . Discussion The trial will provide much needed clinical evidence on the impact of vitamin D supplementation on insulin resistance and secretion and its underlying mechanisms , which are relevant for the prevention and management of type 2 diabetes . Trial registration Clinical trials.gov ID : NCT02112721 Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged Nutraceuticals have generated interest as a way to mitigate the cognitive decline in older adults . The aim of this systematic review was to determine the evidence for these cl aims from the scientific literature in r and omised , double-blinded , controlled trials ( duration : ≥1 year ; participants : n≥100 ; age(mean ) : ≥65 years ) . Following Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines , we search ed four electronic data bases ( PubMed , Scopus , CINAHL and Web of Science ) and identified twenty-five studies published between the 15·June·2006 and 14·June·2016 . Interventions included B-vitamins , n-3 fatty acids , antioxidant vitamins and herbs . Of the B-vitamin studies , four found benefits to cognition with supplementation . The first of these B-vitamin studies , in individuals with mild cognitive impairment ( n 266 ; duration = 2 years ) , included benefit to executive function ( P=0·015 ) and improvements in the Mini-Mental State Examination ( MMSE ) among participants with baseline homocysteine above 11·3 µmol/l ( P<0·001 ) . In the same sample , the second study found cognitive benefits  of B-vitamins dependent on the higher baseline plasma n-3 fatty acid status . The third B-vitamin study ( n 900 ; duration = 2 years ) reported improved performance in immediate ( P=0·046 ) and delayed recall ( P=0·013 ) , whereas the fourth study ( n 856 ; duration = 2 years ) reported slower rate of cognitive decline in the MMSE ( P=0·05 ) . One study investigating DHA treatment ( n 402 ; duration = 1·5 years ) revealed the slower rate of cognitive change in apoE e4 non-carriers ( P=0·03 ) . As only five included studies revealed notable benefits , presently based on the specific compounds explored here , there is not compelling evidence to support the use nutraceuticals to improve cognition in the elderly . Future long-term trials of nutraceuticals should investigate interactions with lifestyle , blood biomarkers and genetic risk factors Objective To compare the safety and efficacy of the dipeptidylpeptidase-4 ( DPP-4 ) inhibitors in patients with type 2 diabetes and inadequate glycemic control . Design Systematic review of r and omized controlled trials ( RCTs ) , health economic evaluation studies , systematic review s , and meta-analyses , followed by primary Bayesian mixed treatment comparison meta-analyses ( MTCs ) , and secondary frequentist direct-comparison meta-analyses using a r and om-effects model . Outcomes were reported as weighted mean change from baseline , or odds ratio ( OR ) with 95 % credible interval . Data sources MEDLINE , MEDLINE In-Process , EMBASE , and BIOSIS via Dialog ProQuest ; Cochrane Central Register of Controlled Trials and Cochrane Data base of Systematic Review s via EBSCO ; four diabetes and two technical congress abstract s ; and health technology assessment organization websites . Eligibility criteria Patients with type 2 diabetes and inadequate glycemic control receiving any pharmacological anti-diabetic treatment . Data extraction and analysis Title/ abstract s were review ed for eligibility , followed by full-text review of publications remaining after first pass . A three-person team filtered articles and an independent review er checked a r and om selection ( 10 % ) of filtered articles . Data extraction and quality assessment of studies were also independently review ed . Five DPP-4 inhibitors ( alogliptin , linagliptin , saxagliptin , sitagliptin , and vildagliptin ) were compared via meta- analysis ( where data were available ) as monotherapy , dual therapy ( plus metformin , sulfonylurea , pioglitazone , or insulin ) , and triple therapy ( plus metformin/sulfonylurea ) . Results The review identified 6,601 articles ; 163 met inclusion criteria and 85 publications from 83 RCTs contained sufficient or appropriate data for analysis . MTCs demonstrated no differences between DPP-4 inhibitors in mean change from baseline in glycosylated hemoglobin ( HbA1c ) or body weight , or the proportions of patients achieving HbA1c < 7 % or experiencing a hypoglycemic event , apart from in patients on alogliptin plus metformin , who achieved HbA1c < 7 % more frequently than those treated with saxagliptin plus metformin [ OR 6.41 ( 95 % CI 3.15–11.98 ) versus 2.17 ( 95 % CI 1.56–2.95 ) ] . Conclusions This systematic review and MTC showed similar efficacy and safety for DPP-4 inhibitors as treatment for type 2 diabetes , either as monotherapy or combination therapy AIMS To analyse the effect on systematic review s in diabetes interventions of including only trials that are indexed in medline , and to assess the impact of adding trials from other data bases and the grey literature . METHODS All systematic review s of diabetes interventions which included a meta- analysis of r and omized controlled trials , and were published since 1996 , were selected . The impact on the meta- analysis of including only those trials indexed in medline , and the effect of then adding trials from other sources , was assessed . Where possible this was measured quantitatively , by redoing the meta- analysis , otherwise a qualitative estimate was made . RESULTS Forty-four systematic review s met our inclusion criteria . There were 120 articles reporting trial data which were not indexed in medline . These came from 52 % of the review s. In 34 % of the review s , basing a meta- analysis on a search of only medline would miss trials that could affect the result . Sources of non- medline data which had the biggest effect on the meta-analyses were journal articles from central and embase ( mainly in Diabetes , Nutrition and Metabolism ) and unpublished data ( mainly from industry ) . The exceptions were journal articles on herbal medicine , mostly indexed in Chinese language data bases . CONCLUSIONS A search of only the medline data base is insufficient for systematic review s of diabetes , because in about 34 % of review s the missed trials could affect the results of the meta- analysis . It is recommended that central ( on the Cochrane Library ) also be search ed . Scanning meeting abstract s , and seeking unpublished data are also recommended if the intervention has only recently been introduced
Vitamin K supplementation did not affect insulin sensitivity as measured by homeostasis model assessment of insulin resistance , fasting plasma glucose , fasting plasma insulin , C-reactive protein , adiponectin , leptin , and interleukin-6 levels .
Our analysis suggests no effect of vitamin K supplementation on insulin sensitivity
OBJECTIVE To perform a systematic review and meta- analysis of r and omized , placebo-controlled trials to assess the effect of vitamin K supplementation on insulin sensitivity .