Effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes: a systematic review of interventional studies Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? Is Self-Monitoring of Blood Glucose Appropriate for All Type 2 Diabetic Patients? Association between circulating 25-hydroxyvitamin D and incident type 2 diabetes: a mendelian randomisation study Regular consumption of vitamin D-fortified yogurt drink (Doogh) improved endothelial biomarkers in subjects with type 2 diabetes: a randomized double-blind clinical trial Efficacy of vitamin D supplementation in depression in adults: a systematic review protocol Vitamin D supplementation in the prevention and management of major chronic diseases not related to mineral homeostasis in adults: research for evidence and a scientific statement from the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO) Role of Vitamin D in Insulin Secretion and Insulin Sensitivity for Glucose Homeostasis Effect of Therapeutic Dose of Vitamin D on Serum Adiponectin and Glycemia in Vitamin D-Insufficient or Deficient Type 2 Diabetic Patients Subclinical inflammation influences the association between vitamin A- and iron status among schoolchildren in Ghana Maternal vitamin D supplementation during pregnancy Diabetes Distress but Not Clinical Depression or Depressive Symptoms Is Associated With Glycemic Control in Both Cross-Sectional and Longitudinal Analyses Effect of vitamin D supplementation on inflammation: protocol for a systematic review Vitamin D Receptor Fok-I Polymorphism Modulates Diabetic Host Response to Vitamin D Intake Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes. Is vitamin D status associated with open-angle glaucoma? A cross-sectional study from South Korea. Nutritional status and subsequent all-cause mortality in men and women aged 75 years or over living in the community. Maternal vitamin D sufficiency and reduced placental gene expression in angiogenic biomarkers related to comorbidities of pregnancy Effect of long-term nutraceutical and dietary supplement use on cognition in the elderly: a 10-year systematic review of randomised controlled trials. Exhaled carbon monoxide levels in atopic asthma: a longitudinal study. Concordance of randomized and nonrandomized studies was unrelated to translational patterns of two nutrient-disease associations. Effect of Vitamin D Supplementation on Glucose Control and Inflammatory Response in Type II Diabetes: A Double Blind, Randomized Clinical Trial Regular Consumption of Both Vitamin D– and Calcium- and Vitamin D–Fortified Yogurt Drink Is Equally Accompanied by Lowered Blood Lipoprotein (a) and Elevated Apoprotein A1 in Subjects with Type 2 Diabetes: A Randomized Clinical Trial
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 BACKGROUND Vitamin-D deficiency and vitamin-D receptor genotype ( VDR ) are risk factors for several disorders with inflammatory components , including coronary heart disease ( CHD ) and diabetes , though the mechanisms involved are unclear . AIM To examine the hypothesis that vitamin D status modulates the matrix metalloproteinase ( MMP ) system in a population with a high prevalence of vitamin D deficiency , a situation affecting susceptibility to CHD and diabetes . DESIGN Prospect i ve cross-sectional , interventional and embedded studies . METHODS Circulating MMP2,9 , the inhibitor TIMP-1 and C-reactive protein ( CRP ) were measured during studies of vitamin-D deficiency as a risk factor for type 2 diabetes and CHD in 171 healthy British Bangladeshi adults , free of known diabetes or major illness .  Vitamin D status , VDR genotype , body-build , blood pressure , lipid and insulin profiles , glucose tolerance , fibrinogen , PAI-1 , folate and homocysteine were measured . Vitamin-D-deficient subjects were re-assessed after 1 years ' supplementation .  MMP , TIMP-1 and CRP levels were measured in 41 subjects halfway through 5-year follow-up . Independent determinants of circulating concentrations of MMP9 , TIMP-1 and CRP were assessed by multiple regression analysis . RESULTS Vitamin D status was the sole determinant of circulating MMP9 ( inversely ) and an independent determinant of CRP ( inversely ) . Determinants of TIMP-1 were MMP9 , systolic blood-pressure ( directly ) and VDR genotype ( TaqI ) . Significant reductions in MMP9 ( -68 % ) , TIMP-1 ( -38 % ) and CRP ( -23 % ) concentrations followed vitamin-D supplementation . DISCUSSION Vitamin-D insufficiency is associated with increased circulating MMP2,9 and CRP , correctable by supplementation . This finding provides a possible mechanism for tissue damage in chronic inflammatory conditions , including CHD and diabetes OBJECTIVE —We sought to determine whether self-monitoring of blood glucose ( SMBG ) is associated with better glycemic control in type 2 diabetes . RESEARCH DESIGN AND METHODS —We used cross-sectional and longitudinal data from type 2 diabetic participants in the observational , community-based Fremantle Diabetes Study ( FDS ) who reported SMBG status at study entry ( n = 1,286 ) and annual review s over 5 years ( n = 531 ) . RESULTS —At study entry , 70 % of patients performed SMBG , with a median of four tests per week ( interquartile range two to seven ) . Patients with shorter diabetes duration ; who were attending diabetes education , diabetes-related clinics , or medical specialists ; who were taking insulin with or without oral hypoglycemic agents ( OHAs ) ; and who were self-reporting hypoglycemic events were more likely to use SMBG . Both cross-sectional and longitudinal FDS data showed that HbA1c ( A1C ) was not significantly different between SMBG users and nonusers , either overall or within diabetes treatment groups ( diet , OHAs , and insulin with or without OHAs ) . There was also no independent cross-sectional relationship between A1C and SMBG frequency . The average annual societal cost of using SMBG ( in year 2000 Australian dollars [ A$ ] , excluding glucometers ) was A$ 162 per type 2 diabetic patient or A$ 51 million when projected to the Australian diagnosed type 2 diabetic population . CONCLUSIONS —Neither SMBG testing nor its frequency was associated with glycemic benefit in type 2 diabetic patients regardless of treatment . Our data did not include methods of SMBG delivery and application , factors that require further assessment in the evaluation of SMBG utility in non – insulin-treated type 2 diabetes . SMBG may be still of value in the identification and prevention of hypoglycemia and in dose adjustment in insulin-treated patients Summary Background Low circulating concentrations of 25-hydroxyvitamin D ( 25[OH]D ) , a marker of vitamin D status , are associated with an increased risk of type 2 diabetes  , but whether this association is causal remains unclear . We aim ed to estimate the unconfounded , causal association between 25(OH)D concentration and risk of type 2 diabetes using a mendelian r and omisation approach . Methods Using several data sources from population s of European descent , including type 2 diabetes cases and non-cases , we did a mendelian r and omisation analysis using single nucleotide polymorphisms ( SNPs ) within or near four genes related to 25(OH)D synthesis and metabolism : DHCR7 ( related to vitamin D synthesis ) , CYP2R1 ( hepatic 25-hydroxylation ) , DBP ( also known as GC ; transport ) , and CYP24A1 ( catabolism ) . We assessed each SNP for an association  with circulating 25(OH)D concentration ( 5449 non-cases ; two studies ) , risk of type 2 diabetes ( 28 144 cases , 76 344 non-cases ; five studies ) , and glycaemic traits ( concentrations of fasting glucose , 2-h glucose , fasting insulin , and HbA1c  ; 46 368 non-cases ; study consortium ) . We combined these associations in a likelihood-based mendelian r and omisation analysis to estimate the causal association of 25(OH)D concentration with type 2 diabetes and the glycaemic traits , and compared them with that from a meta- analysis of data from observational studies ( 8492 cases , 89 698 non-cases ; 22 studies ) that assessed the association between 25(OH)D concentration and type 2 diabetes . Findings All four SNPs were associated with 25(OH)D concentrations ( p<10−6 ) . The mendelian r and omisation-derived unconfounded odds ratio for type 2 diabetes was 1·01 ( 95 % CI 0·75–1·36 ; p=0·94 ) per 25·0 nmol/L ( 1 SD ) lower 25(OH)D concentration . The corresponding ( potentially confounded ) relative risk from the meta- analysis of data from observational studies was 1·21 ( 1·16–1·27 ; p=7·3 × 10−19 ) . The mendelian r and omisation-derived estimates for glycaemic traits were not significant ( p>0·25 ) . Interpretation The association between 25(OH)D concentration and type 2 diabetes is unlikely to be causal . Efforts to increase 25(OH)D concentrations might not reduce the risk of type 2 diabetes as would be expected on the basis of observational evidence . These findings warrant further investigations to identify causal factors that might increase 25(OH)D concentration and also reduce the risk of type 2 diabetes . Funding UK Medical Research Council Epidemiology Unit and European Union Sixth Framework Programme Background Endothelial dysfunction has been proposed as the underlying cause of diabetic angiopathy that eventually leads to cardiovascular disease , the major cause of death in diabetes . We recently demonstrated the ameliorating effect of regular vitamin D intake on the glycemic status of patients with type 2 diabetes ( T2D ) . In this study , the effects of improvement of vitamin D status on glycemic status , lipid profile and endothelial biomarkers in T2D subjects were investigated . Methods Subjects with T2D were r and omly allocated to one of the two groups to receive either plain yogurt drink ( PYD ; containing 170 mg calcium and no vitamin D/250 mL , n1 = 50 ) or vitamin D3-fortified yogurt drink ( FYD ; containing 170 mg calcium and 500 IU/250 mL , n2 = 50 ) twice a day for 12 weeks . Anthropometric measures , glycemic status , lipid profile , body fat mass ( FM ) and endothelial biomarkers including serum endothelin-1 , E-selectin and matrix metalloproteinase (MMP)-9 were evaluated at the beginning and after the 12-week intervention period . Results The intervention result ed in a significant improvement in fasting glucose , the Quantitative Insulin Check Index ( QUICKI ) , glycated hemoglobin ( HbA1c ) , triacylglycerols , high-density lipoprotein cholesterol ( HDL-C ) , endothelin-1 , E-selectin and MMP-9 in FYD compared to PYD ( P < 0.05 , for all ) . Interestingly , difference in changes of endothelin-1 , E-selectin and MMP-9 concentrations in FYD compared to PYD ( -0.35 ± 0.63 versus -0.03 ± 0.55 , P = 0.028 ; -3.8 ± 7.3 versus 0.95 ± 8.3 , P = 0.003 and -2.3 ± 3.7 versus 0.44 ± 7.1 ng/mL , respectively , P < 0.05 for all ) , even after controlling for changes of QUICKI , FM and waist circumference , remained significant for endothelin-1 and MMP-9 ( P = 0.009 and P = 0.005 , respectively ) but disappeared for E-selectin ( P = 0.092 ) . On the contrary , after controlling for serum 25(OH)D , the differences disappeared for endothelin-1(P = 0.066 ) and MMP-9 ( P = 0.277 ) but still remained significant for E-selectin ( P = 0.011 ) . Conclusions Ameliorated vitamin D status was accompanied by improved glycemic status , lipid profile and endothelial biomarkers in T2D subjects . Our findings suggest both direct and indirect ameliorating effects of vitamin D on the endothelial biomarkers . Trial registration Clinical Trials.gov : 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 Optimal vitamin D status promotes skeletal health and is recommended with specific treatment in individuals at high risk for fragility fractures . A growing body of literature has provided indirect and some direct evidence for possible extraskeletal vitamin D-related effects . Purpose and Methods Members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis have review ed the main evidence for possible proven benefits of vitamin D supplementation in adults at risk of or with overt chronic extra-skeletal diseases , providing recommendations and guidelines for future studies in this field . Results and conclusions Robust mechanistic evidence is available from in vitro studies and in vivo animal studies , usually employing cholecalciferol , calcidiol or calcitriol in pharmacologic rather than physiologic doses . Although many cross-sectional and prospect i ve association studies in humans have shown that low 25-hydroxyvitamin D levels ( i.e. , < 50 nmol/L ) are consistently associated with chronic diseases , further strengthened by a dose-response relationship , several meta-analyses of clinical trials have shown contradictory results . Overall , large r and omized controlled trials with sufficient doses of vitamin D are missing , and available small to moderate-size trials often included people with baseline levels of serum 25-hydroxyvitamin D levels  > 50 nmol/L , did not simultaneously assess multiple outcomes , and did not report overall safety ( e.g. , falls ) . Thus , no recommendations can be made to date for the use of vitamin D supplementation in general , parental compounds , or non-hypercalcemic vitamin D analogs in the prevention and treatment of extra-skeletal chronic diseases . Moreover , attainment of serum 25-hydroxyvitamin D levels well above the threshold desired for bone health can not be recommended based on current evidence , since safety has yet to be confirmed . Finally , the promising findings from mechanistic studies , large cohort studies , and small clinical trials obtained for autoimmune diseases ( including type 1 diabetes , multiple sclerosis , and systemic lupus erythematosus ) , cardiovascular disorders , and overall reduction in mortality require further confirmation 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 Background : Lower vitamin D status has been reported in diabetic patients . Serum 25-hydroxyvitamin D and adiponectin were inversely associated with type 2 diabetes and insulin resistance . Vitamin D may involve in regulation of the adiponectin levels , which is directly related to insulin sensitivity . Objectives : The aim of this study was to investigate the effect of therapeutic dose of vitamin D on serum adiponectin and insulin resistance in vitamin D-insufficient or deficient type 2 diabetic patients . Material s and Methods : This double-blind , r and omized , clinical trial was conducted on 81 type 2 diabetic patients with vitamin D level of 10 - 30 ng/mL. Intervention was 50000 IU vitamin D or placebo once a week for 8 weeks . At the beginning and end of the study , blood sample s were collected after 12 hours of fasting and serum glucose , insulin , 25-hydroxyvitamin D , and adiponectin were measured . Insulin resistance was calculated by homeostasis model assessment ( HOMA-IR ) . Results : After 8-week intervention , serum 25-hydroxyvitamin D significantly increased and reached the normal levels in patients receiving vitamin D ( P < 0.001 ) and the levels of fasting serum glucose , insulin , and HOMA-IR were significantly decreased ( P = 0.04 , 0.02 and 0.007 , respectively ) . No significant changes were observed in these levels in the placebo group . Significant differences were observed in mean changes in the above-mentioned variables between the two groups ( P = 0.01 , 0.04 and 0.006 , respectively ) . No significant changes were found in serum adiponectin in the vitamin D and placebo groups ( P = 0.83 ) . Conclusions : Therapeutic dose of vitamin D can improve vitamin D status and glycemic indicators . But it seems that an 8-week intervention period was not sufficient to reveal the possible effects of vitamin D on serum adiponectin levels Background and objective In re source -poor setting s , micronutrient deficiencies such as vitamin A deficiency may co-exist with iron-deficiency . In this study we assessed the iron and vitamin A status of schoolchildren and the association between vitamin A and iron status . Methods A cross-sectional design using the baseline data of a dietary intervention trial conducted among r and omly selected 5–12 years old schoolchildren ( n = 224 ) from 2 rural schools in northern Ghana .  Hemoglobin ( Hb ) , serum ferritin ( SF ) and serum transferrin receptor ( sTfR ) concentrations were used as measures of iron status . Retinol binding protein ( RBP ) was used as a measure of vitamin A status . Sub clinical inflammation ( SCI ) was measured using C-reactive protein ( CRP ) and α1-acid glycoprotein ( AGP ) concentrations . We examined the cross-sectional association between vitamin A and iron status biomarkers with multiple linear regressions . Results The proportions of schoolchildren with anemia ( WHO criteria ) , iron-deficiency ( ID , SF < 15μg/l and /or sTfR > 8.5mg/l ) and  iron-deficiency anemia  ( IDA , concurrent anemia and ID ) were 63.8 % , 68.3 % and 46.4 % respectively . Low or marginal vitamin A status ( 0.70 μmol/l ≤ RBP < 1.05μmol/l ) was present in 48.2 % while 37.5 % of the schoolchildren had vitamin A deficiency ( VAD , RBP < 0.70 μmol/l ) . The prevalence of SCI as well as concurrent VAD and ID were 48.7 % and 25 % respectively . RBP was associated with Hb ( β = 7.2 , P = 0.05 ) but not SF ( β = 20.7 , P = 0.33 ) and sTfR concentration ( β = 12.0 , P = 0.63 ) . In the presence of SCI , RBP was not associated with hemoglobin status but a significant positive association was observed among children without SCI . Conclusions The study shows that RBP is significantly associated with Hb concentration but not with SF and sTfR. The observed relationship between RBP and Hb is only significant in the absence of SCI 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 OBJECTIVE To determine the concurrent , prospect i ve , and time-concordant relationships among  major depressive disorder ( MDD ) , depressive symptoms , and diabetes distress with glycemic control . RESEARCH DESIGN AND METHODS In a noninterventional study , we assessed 506 type 2 diabetic patients for MDD ( Composite International Diagnostic Interview ) , for depressive symptoms ( Center for Epidemiological Studies -Depression ) , and for diabetes distress ( Diabetes Distress Scale ) , along with self-management , stress , demographics , and diabetes status , at baseline and 9 and 18 months later . Using multilevel modeling ( MLM ) , we explored the cross-sectional relationships of the three affective variables with A1C , the prospect i ve relationships of baseline variables with change in A1C over time , and the time-concordant relationships with A1C . RESULTS All three affective variables were moderately intercorrelated , although the relationship between depressive symptoms and diabetes distress was greater than the relationship of either with MDD . In the cross-sectional MLM , only diabetes distress but not MDD or depressive symptoms was significantly associated with A1C . None of the three affective variables were linked with A1C in prospect i ve analyses . Only diabetes distress displayed significant time-concordant relationships with A1C . CONCLUSIONS We found no concurrent or longitudinal association between MDD or depressive symptoms with A1C , whereas both concurrent and time-concordant relationships were found between diabetes distress and A1C . What has been called “ depression ” among type 2 diabetic patients may really be two conditions , MDD and diabetes distress , with only the latter displaying significant associations with A1C . Ongoing evaluation of both  diabetes distress and MDD may be helpful in clinical setting 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 OBJECTIVE Inter population as well as interindividual variations in response to vitamin D intake commonly observed in subjects with type 2 diabetes may be related to genetic makeup . One of the c and i date genes potentially responsible for this diversity is vitamin D receptor ( VDR ) . This study aim ed to investigate the interactive effect of VDR Fok-I polymorphism and vitamin D intake on diverse aspects of diabetic host response . RESEARCH DESIGN AND METHODS Glycemic status , lipid profiles , inflammatory biomarkers , and VDR Fok-I genotypes were determined in diabetic subjects ( n = 140 ) who participated in a r and omized controlled trial . Participants consumed two 250-mL bottles per day of yogurt drink ( doogh ) fortified with 500 IU vitamin D/250 mL for 12 weeks . RESULTS Mean serum 25(OH)D increased by ~30 nmol/L ( P < 0.001 ) . The time × intervention effect was significant for 25(OH)D ( P = 0.030 ) , HDL ( P = 0.011 ) , high-sensitivity C-reactive protein ( hsCRP ) ( P < 0.001 ) , interleukin (IL)-4 ( P = 0.008 ) , and IL-6 ( P = 0.017 ) among the genotypic groups . The alleles were defined as ‘ ‘ F ’ ’ or ‘ ‘ f ’ ’ depending on the absence or presence of the restriction site , respectively . The least increment in 25(OH)D was in ff ( 23.0 ± 3.8 nmol/L ) compared with Ff ( 31.2 ± 3.4 nmol/L ) and FF ( 35.6 ± 2.7 nmol/L ) ( P for trend = 0.009 ) , but only the difference between ff and FF was significant ( P = 0.023 ) . FF group had the largest decrement of both hsCRP and IL-6 compared with Ff ( P < 0.001 and P = 0.038 ) and ff ( P = 0.010 and P = 0.048 ) , respectively . CONCLUSIONS We concluded that those of VDR ff genotype may be regarded as “ low responders ” to vitamin D intake in terms of response of circulating 25(OH)D and certain inflammatory biomarkers . A nutrigenetic approach may , therefore , be needed to protect diabetic patients from vitamin D deficiency BACKGROUND Suboptimal vitamin D status is associated with endothelial dysfunction and an increased risk of cardiovascular diseases but it is unclear whether vitamin D supplementation is beneficial . The aim was to investigate the effect of vitamin D supplementation on endothelial function in patients with type 2 diabetes mellitus ( DM ) . METHODS In a double-blind , placebo-controlled trial , we r and omized 100 type 2 DM patients to vitamin D supplement  ( 5000 IU/day , n = 50 ) or placebo ( controls , n = 50 ) for 12 weeks . Assessment of vascular function with brachial artery flow-mediated dilatation ( FMD ) , circulating levels of endothelial progenitor cells ( EPCs ) and brachial-ankle pulse wave velocity , and metabolic parameter , high-sensitivity C-reactive protein ( hsCRP ) and oxidative stress markers were performed before and after the supplementation . RESULTS After 12 weeks , vitamin D treated patients had significant increases in serum 25-hydroxyvitamin D [ 25(OH)D ] concentration ( treatment effect 34.7 ng/mL , 95 % CI 26.4 - 42.9 , P < 0.001 ) and serum ionized calcium ( treatment effect 0.037 mmol/L , 95 % CI 0.007 - 0.067 , P = 0.018 ) ; decreased serum parathyroid hormone concentration ( treatment effect -0.55 pmol/L , 95 % CI -1.08 to -0.02 , P = 0.042 ) compared to patients who received placebo . Nevertheless , vitamin D supplementation did not improve vascular function as determined by FMD , circulating EPC count or baPWV ( all P > 0.05 ) . Furthermore , hsCRP , oxidative stress markers , low- and high-density lipoprotein and glycated hemoglobin were also similar between two groups ( all P > 0.05 ) . CONCLUSION In patients with type 2 DM , 12 weeks oral supplementation of vitamin D did not significantly affect vascular function or serum biomarkers of inflammation and oxidative stress . CLINICAL TRIAL NUMBER HKCTR-867 , www.hk clinical trials.com OBJECTIVE Open-angle glaucoma ( OAG ) is one of the major chronic diseases involving the optic nerve . However , little is known about the association between vitamin D and OAG . The present study was conducted to test the hypothesis that lower vitamin D status is associated with greater prevalence of OAG . DESIGN Cross-sectional study . Multivariable logistic regression was performed to examine the relationship between serum 25-hydroxyvitamin D ( 25(OH)D ) and OAG after adjusting for traditional potential confounders . OAG was defined by the criteria of the International Society for Geographical and Epidemiological Ophthalmology . SETTING The Fifth Korean National Health and Nutrition Examination Survey conducted in 2010 - 2011 . SUBJECTS Six thous and and ninety-four adult participants r and omly selected from 192 surveys in 131 locations in South Korea . RESULTS Multivariable-adjusted odds ratios of OAG across quintiles of decreasing 25(OH)D were 1.26 , 1.00 ( reference ) , 1.31 , 1.36 and 1.69 ( P for quadratic trend < 0.01 ) . The odds ratio for the lowest 25(OH)D quintile was significantly higher than that for the second quintile ( P < 0.01 ) . In addition , we discovered that the predictors for worsening of OAG , such as intraocular pressure or vertical and horizontal cup-to-disc ratios , had a significant relationship with 25(OH)D level . CONCLUSIONS There was a reverse J-shaped association between 25(OH)D levels and the risk of OAG , with significantly elevated risk at lower 25(OH)D. The findings of this research suggest that vitamin D deficiency should be considered as a potential risk factor for the development of OAG . To our knowledge , the present study is the first one that shows an association between vitamin D status and OAG We prospect ively investigated relationships between blood markers of Fe , vitamin B12 , folate , vitamin C and vitamin D status and subsequent  all-cause mortality  in 208 men and 191 women aged 75 years or over living in the community in Aberdeen , Scotl and . The participants had been recruited for a cross-sectional study in 1999 - 2000 when they completed health and lifestyle question naires  and had blood sample s taken for analysis of serum ferritin , serum vitamin B12 , erythrocyte folate , plasma vitamin C and serum 25-hydroxycholecalciferol .  Mortality was ascertained on national data bases up to December 2005 , with a median time of follow up of 69.2 ( range 1.0 - 79.9 ) months . Participants were divided into sex-specific quintiles of baseline levels for each nutrient , and hazard ratios were estimated with Cox proportional hazard models adjusted for age and sex with the significance of linear trends in the associations assessed by logistic regression . There was no significant association between blood markers of Fe , vitamin B12 or folate status at baseline and mortality , but  vitamin D status at baseline was inversely related to mortality ( P for trend < 0.001 ) . For vitamin C there was no evidence of a linear trend but participants in the lowest quintile of plasma levels had a significantly higher risk of death than those in the highest quintile . R and omized controlled trials of lifestyle changes which improve vitamin status are needed to assess whether these associations could be causal INTRODUCTION Maternal circulating 25-hydroxyvitamin D [ 25(OH)D ] has been shown to optimize production of 1,25-dihydroxyvitamin D [ 1,25(OH)2D ] during pregnancy at approximately 100nmoles/L , which has pronounced effects on fetal health outcomes . Additionally , associations are noted between low maternal 25(OH)D concentrations and vascular pregnancy complications , such as preeclampsia . To further eluci date the effects of vitamin D activity in pregnancy , we investigated the role of maternal 25(OH)D , the nutritional indicator of vitamin D status , in relation to placental maintenance and , specifically , expression of placental gene targets related to angiogenesis and vitamin D metabolism . METHODS A focused analysis of placental mRNA expression related to angiogenesis , pregnancy maintenance , and vitamin D metabolism was conducted in placentas from 43 subjects enrolled in a r and omized controlled trial supplementing 400IU or 4400IU of vitamin D3 per day during pregnancy . Placental mRNA was isolated from biopsies within one hour of delivery , followed by quantitative PCR . We classified pregnant women with circulating concentrations of < 100nmoles/L as deficient and those with ≥100nmoles/L as sufficient . The value of each gene 's change in the PCR cycle threshold ( ΔCT ) , which is a relative measure of target concentration , was compared with maternal 25(OH)D concentrations < 100nmoles/L and ≥100nmoles/L based on a two- sample Wilcoxon test . RESULTS Soluble FMS-like tyrosine kinase 1 ( sFlt-1 ) and vascular endothelial growth factor ( VEGF ) gene expression was significantly downregulated in the maternal subgroup with circulating 25(OH)D ≥100ng/mL compared to the subgroup < 100ng/mL. DISCUSSION Here , we report a significant association between maternal vitamin D status and the expression of sFlt-1 and VEGF at the mRNA level . Achieving maternal circulating 25(OH)D ≥100nmoles/L suggests the impact of maternal vitamin D3 supplementation on gene transcription in the placenta , thereby potentially decreasing antiangiogenic factors that may contribute to vascular pregnancy complications 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 Exhaled carbon monoxide ( eCO ) is a potential non-invasive marker of airway inflammation . We have investigated the cross-sectional and longitudinal relationship between eCO and lung function and bronchial reactivity in 69 adults with atopic asthma , in the course of participation in a 6-week r and omised placebo-controlled trial of vitamin E supplementation .  At baseline , there was no cross-sectional association between absolute eCO levels and either forced expiratory volume ( FEV(1 ) ) , forced vital capacity ( FVC ) or bronchial reactivity . However , in the longitudinal analysis within the placebo group , a rise in mean eCO was significantly associated with improvement in bronchial reactivity ( change in eCO ( parts per million ) per natural log unit change in bronchial hyperreactivity 0.498 , 95 % confidence interval 0.071 to 0.924 , P=0.024 ) . These findings suggest that , contrary to previous data , there is no cross-sectional relationship between eCO and lung function or bronchial reactivity , but that there may be a longitudinal trend with bronchial reactivity that is worth further investigation OBJECTIVE There are several examples in nutrition of discordance between the results of observational studies and r and omized controlled trials ( RCTs ) . We hypothesized that this discordance is attributable to differences in the translational paths of nutrient-disease associations . Translational paths can be assessed using citation analysis . STUDY DESIGN AND SETTING We compared the characteristics of citation networks using examples , where RCTs and observational studies agreed ( long-chain n-3 polyunsaturated fatty acids [ n-3 PUFA ] ) or disagreed ( vitamin E ) . We performed systematic review s in each example , constructed citation networks , and compared them with respect to the number of articles and citation relationships between them , as well as the distribution of articles ' hub and authority scores . RESULTS For n-3 PUFA , meta-analyses of 14 RCTs and 10 observational studies both suggested that higher intake was associated with lower cardiovascular mortality . For vitamin E , the meta- analysis of 14 RCTs excluded a clinical ly significant effect , whereas 14 observational studies reported a significant inverse association . The respective citation networks consisted of 392 ( n-3 PUFA ) and 351 ( vitamin E ) articles . No differences between the characteristics of the two networks were identified . There was no evidence that the observational studies pre date d RCTs in the translational process in either example . CONCLUSION In the two examples , citation network characteristics do not predict concordance in the results of observational studies and RCTs Background : Diabetes mellitus ( DM ) and vitamin D deficiency are major health concerns around the world . Evidence suggests a possible role of vitamin D in improvement of insulin secretion and sensitivity . Objectives : We assessed whether vitamin D supplementation could be used in vitamin D deficient-type II diabetes to improve glucose metabolism , components of metabolic syndrome ( MetS ) and specific inflammatory biomarkers . Patients and Methods : A double blind , r and omized clinical trial was conducted in King Khalid University Hospital , Saudi Arabia to evaluate the effect of cholecalciferol supplementation on glycemic control , MetS components and specific inflammatory biomarkers including tumor necrosis factor-alpha ( TNF-α ) , Interleukin ( IL-6 ) , leptin , adiponectin and vascular cell adhesion molecule-1 ( VCAM-1 ) . Twenty-two patients with type II diabetes with insulin resistance , glycated hemoglobin ( HbA1c ) ≥ 6 ( 42 mmol/mol ) and serum 25(OH)D < 50 nmol/L were r and omized using a computer program to receive either supplementation with cholecalciferol ( 5000 IU/day ) or placebo for 12 weeks . The primary outcome was change in HbA1c levels from baseline . Results : Median [ IQR ] 25(OH)D levels increased significantly in the vitamin D group as 58.1 [ 48 , 67.3 ] nmol/L ( P = 0.002 ) . There was no significant difference in the change of HbA1c between the groups ( P = 0.5 ) with a decrease of -0.1 % [ -1 , 0.5 ] in the vitamin D group and an increase of 0.15 % [ 0.1 , 0.2 ] in the placebo group . A significant improvement was observed in the homeostasis model of assessment of β-cell activity ( HOMA-%B ) ( P = 0.03 ) with vitamin D supplementation compared to baseline . Conclusions : Vitamin D repletion for 12 weeks increased serum vitamin D concentrations and improved β-cell activity in vitamin D-deficient type II diabetes with no significant changes in HbA1c or insulin sensitivity Objective : Cardiovascular disease ( CVD ) is the major morbidity and cause of death in diabetic subjects . Observational studies have shown the association of low vitamin D status with poor glycemic control , atherogenic lipid profile , and CVD . However , the possible link between circulating 25-hydroxycholecalciferol and apoproteins ( Apo A1 and B ) and the atherogenic lipoprotein ( a ) [ Lp(a ) ] has not been documented to date . Methods : Ninety subjects with type 2 diabetes ( T2D ) aged 30–60 years from both sexes were r and omly allocated to one of the 3 groups to receive 2 bottles a day of either ( 1 ) plain doogh ( PD ; containing 150 mg calcium and no detectable vitamin D/250 mL ) ; ( 2 ) vitamin D – fortified doogh ( DD ; containing 150 mg calcium and 500 IU vitamin D/250 mL ) ; or ( 3 ) calcium- and vitamin D – fortified doogh ( CDD ; containing 250 mg calcium and 500 IU vitamin D/250 mL ) for 12 weeks . Anthropometric , dietary , and laboratory assessment s , including Apo A1 , Apo B , and Lp(a ) , were done . Results : Improvement of  vitamin  D status in DD and CDD groups , compared to PD , result ed in a significant increase in Apo A1 ( mean changes 0.22 ± 0.38 , 0.20 ± 0.27 and 0.01 ± 0.35 g/L , respectively , p = 0.047 ) and a significant decrease in serum Lp(a ) ( mean changes −0.08 ± 0.30 , −0.08 ± 0.31 , and 0.14 ± 0.25 μmol/L , respectively , p = 0.011 ) . There was no significant difference between DD and CDD groups . Serum Apo B did not change significantly in any of the groups . Conclusions : Significant amelioration of serum Apo A1 and Lp(a ) following improvement of vitamin D status in T2D subjects may have preventive implication s against long-term diabetic complications , notably CVD . This trial was registered at Clinical Trials.gov as NTC01229891
This meta- analysis concludes that hypovitaminosis D is associated with increased risk of hyperglycemia both in diabetic and non-diabetic subjects .
There is evidence that vitamin D status is associated with type 2 diabetes .
Many observational studies have been performed investigating the relationship of vitamin D status and circulating biomarkers of glycemic regulation .
To find out whether this association holds , we conducted a systematic review and meta- analysis of cross sectional and longitudinal studies .