title: Vitamin D supplementation in obese type 2 diabetes subjects in Ajman, UAE: a randomized controlled double-blinded clinical trial Effect of paricalcitol on endothelial function and inflammation in type 2 diabetes and chronic kidney disease. Serum IL-18 and hsCRP correlate with insulin resistance without effect of calcitriol treatment on type 2 diabetes. Effects of vitamin D-fortified low fat yogurt on glycemic status, anthropometric indexes, inflammation, and bone turnover in diabetic postmenopausal women: A randomised controlled clinical trial. No effects of oral vitamin D supplementation on non-alcoholic fatty liver disease in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial A randomised controlled trial evaluating the impact of targeted vitamin D supplementation on endothelial function in type 2 diabetes mellitus: The DIMENSION trial The effect of high-dose vitamin D supplementation on insulin resistance and arterial stiffness in patients with type 2 diabetes Effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes: a systematic review of interventional studies The effect of a single dose of vitamin D on glycemic status and C-reactive protein levels in type 2 diabetic patients with ischemic heart disease: a randomized clinical trial Regular consumption of vitamin D-fortified yogurt drink (Doogh) improved endothelial biomarkers in subjects with type 2 diabetes: a randomized double-blind clinical trial Vitamin D receptor activation with calcitriol for reducing urinary angiotensinogen in patients with type 2 diabetic chronic kidney disease Effect of Vitamin D Supplementation on Glucose Control and Inflammatory Response in Type II Diabetes: A Double Blind, Randomized Clinical Trial Effect of vitamin D supplementation on inflammation: protocol for a systematic review Improvement of vitamin D status via daily intake of fortified yogurt drink either with or without extra calcium ameliorates systemic inflammatory biomarkers, including adipokines, in the subjects with type 2 diabetes. Effect of Therapeutic Dose of Vitamin D on Serum Adiponectin and Glycemia in Vitamin D-Insufficient or Deficient Type 2 Diabetic Patients Vitamin D deficiency, serum leptin and osteoprotegerin levels in older diabetic patients: an input to new research avenues Calcium-vitamin D cosupplementation influences circulating inflammatory biomarkers and adipocytokines in vitamin D-insufficient diabetics: a randomized controlled clinical trial. Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes. The Effect of Vitamin D Supplementation on Adiposity, Blood Glycated Hemoglobin, Serum Leptin and Tumor Necrosis Factor-α in Type 2 Diabetic Patients Effect of vitamin D supplementation in type 2 diabetes patients with pulmonary tuberculosis. The Effect of Vitamin D Supplementation on Inflammatory and Hemostatic Markers and Disease Activity in Patients with Systemic Lupus Erythematosus: A Randomized Placebo-controlled Trial Effect of high doses of vitamin D on arterial properties, adiponectin, leptin and glucose homeostasis in type 2 diabetic patients. Lack of effect of subtherapeutic vitamin D treatment on glycemic and lipid parameters in Type 2 diabetes: A pilot prospective randomized trial. Investigating the causal effect of vitamin D on serum adiponectin using a mendelian randomization approach
abstract: Objectives : To study the effect of Vitamin D3 supplementation on metabolic control in an obese type 2 diabetes Emirati population . Methods : This r and omized double-blind clinical trial was conducted with 87 vitamin D-deficient obese , type 2 diabetic participants . The vitamin D-group ( n=45 ) and the placebo group ( n=42 ) were matched for gender , age , HbA1c and 25-hydroxy vitamin D ( 25(OH ) D ) at the baseline . The study was divided into two phases of 3 months each ; in phase 1 , the vitamin D-group received 6000 IU vitamin D3/day followed by 3000 IU vitamin D3/day in phase 2 , whereas the placebo group ( n=42 ) received matching placebo . Results : After supplementation , serum 25(OH ) D peaked in the vitamin D-group in phase 1 ( 77.2±30.1 nmol/l , P=0.003 ) followed by a decrease in the phase 2 ( 61.4±18.8 nmol/l , P=0.006 ) , although this was higher compared with baseline . In the placebo group , no difference was observed in the serum 25(OH ) D levels throughout the intervention . Relative to baseline serum , parathyroid hormone decreased 24 % ( P=0.003 ) in the vitamin D-group in phase 2 , but remained unchanged in the placebo group . No significant changes were observed in blood pressure , fasting blood glucose , HbA1c , C-peptide , creatinine , phosphorous , alkaline phosphatase , lipids , C-reactive protein or thyroid stimulating hormone concentrations compared with baseline in either group . Conclusions : Six months of vitamin D3 supplementation to vitamin D-deficient obese type 2 diabetes patients in the UAE normalized the vitamin D status and reduced the incidence of eucalcemic parathyroid hormone elevation but showed no effect on the metabolic control AIMS Patients with type 2 diabetes ( T2DM ) and chronic kidney disease ( CKD ) have impaired endothelial function . Vitamin D and its analogs may play a role in regulation of endothelial function and inflammation . We studied effects of paricalcitol compared to placebo on endothelial function and markers of inflammation and oxidative stress in patients with T2DM and CKD . METHODS A double blind , r and omized , placebo-controlled trial was conducted in 60 patients with T2DM and stage 3 or 4 CKD .  Paricalcitol 1 mcg or placebo was administered orally once daily for three months . Brachial artery flow mediated dilatation ( FMD ) , nitroglycerine mediated dilation ( NMD ) , and plasma concentrations of inflammatory cytokines , tumor necrosis factor -α and interleukin-6 , highly-sensitive C-reactive protein ; endothelial surface proteins , intercellular adhesion molecule -1 and monocyte chemo attractant protein-1 , and plasma glucose , insulin , free fatty acids , and urinary isoprostane were measured at baseline and end of three months . RESULTS 27 patients in the paricalcitol group and 28 patients in the control group completed the study , though analysis of FMD at both time points was possible in 23 patients in each group . There was no significant difference in the change in FMD , NMD or the biomarkers examined after paricalcitol or placebo treatment . CONCLUSIONS Treatment with paricalcitol at this dose and duration did not affect brachial artery FMD or biomarkers of inflammation and oxidative stress . The lack of significance may be due to the fact that the study patients had advanced CKD and that effects of paricalcitol are not additive to the effects of glycemic , lipid and anti-hypertensive therapies BACKGROUND Chronic low- grade systemic inflammation presented in Type 2 diabetes mellitus plays a major role in disease progression as well as development of micro- and macro-vascular complications of diabetes . Therefore , reducing inflammation can be beneficial in prevention of diabetes complications . OBJECTIVES To investigate the association between insulin resistance and inflammatory markers , and assessing the effects of oral Calcitriol on inflammatory cytokines in type 2 diabetic patients . METHODS In this double-blind r and omized placebo-controlled trial , 70 participants with type-2 diabetes were r and omly divided to two groups . One group received two capsules of Calcitriol ( 0.25 μg 1,25-dihydroxy cholecalciferol per each capsule ) per day . The second group received placebo tablets . At the beginning of the study , we assessed insulin resistance and its relation to inflammatory profile . Serum high sensitive C-reactive protein ( hs CRP ) , interleukin-6 and interleukin-18 were also measured at the beginning and the end of the 12-week supplementation trial . RESULTS Mean calcium , phosphorus and vitamin D concentrations in the study participants were 8.98 ± 0.79 mg/dL , 3.86 ± 0.50 mg/dL and 40.91 ± 30.9 ng/mL , respectively . IL-18 and hsCRP had significant positive associations with insulin resistance markers and negative associations with insulin sensitivity markers . At the end of the 12-week supplementation trial , no significant difference was seen in serum levels of hsCRP , IL-6 and IL-18 between the two groups , while these values were adjusted for baseline values . CONCLUSION Inflammation was associated with insulin resistance in diabetic patients . No anti-inflammatory effect of Calcitriol in terms of decreasing hsCRP , IL-6 and IL-18 detected BACKGROUND & AIMS Low levels of serum 25-hydroxy vitamin D ( 25(OH)D ) are common in type 2 diabetic patients and cause several complications particularly , in postmenopausal women due to their senile and physiological conditions . This study aim ed to assess the effects of vitamin D-fortified low fat yogurt on glycemic status , anthropometric indexes , inflammation , and bone turnover in diabetic postmenopausal women . METHODS In a r and omized , placebo-controlled , double-blind parallel-group clinical trial , 59 postmenopausal women with type 2 diabetes received fortified yogurt ( FY ; 2000 IU vitamin D in 100 g/day ) or plain yogurt  ( PY ) for 12 weeks . Glycemic markers , anthropometric indexes , inflammatory , and bone turnover markers were assessed at baseline and after 12 weeks . RESULTS After intervention , in FY group ( vs PY group ) , were observed : significant increase in serum 25(OH)D and decrease of PTH ( stable values in PY ) ; significant improvement in serum fasting insulin , HOMA-IR , HOMA-B , QUICKI , and no changes in serum fasting glucose and HbA1c ( significant worsening of all indexes in PY ) ; significant improvement in WC , WHR , FM , and no change in weight and BMI ( stable values in PY ) ; significant increase of omentin ( stable in PY ) and decrease of sNTX ( significant increase in PY ) . Final values of glycemic markers ( except HbA1c ) , omentin , and bone turnover markers significantly improved in FY group compared to PY group . Regarding final values of serum 25(OH)D in FY group , subjects were classified in insufficient and sufficient categories . Glycemic status improved more significantly in the insufficient rather than sufficient category ; whereas the other parameters had more amelioration in the sufficient category . CONCLUSIONS Daily consumption of 2000 IU vitamin D-fortified yogurt for 12 weeks improved glycemic markers ( except HbA1c ) , anthropometric indexes , inflammation , and bone turnover markers in postmenopausal women with type 2 diabetes . TRIAL REGISTRATION www.i rct .ir ( I RCT 2013110515294N1 ) Background Non-alcoholic fatty liver disease ( NAFLD ) is the most common hepatic disorder worldwide , reaching prevalence up to 90 % in obese patients with type 2 diabetes ( T2D ) , and representing an independent risk factor for cardiovascular mortality . Furthermore , the coexistence of T2D and NAFLD leads to higher incidence of diabetes ’ complications and additive detrimental liver outcomes . The existence of a close association between NAFLD and hypovitaminosis D , along with the anti-inflammatory and insulin-sensitizing properties of vitamin D , have been largely described , but vitamin D effects on hepatic fat content have never been tested in a r and omized controlled trial . We assessed the efficacy and safety of 24-week oral high-dose vitamin D supplementation in T2D patients with NAFLD . Methods This r and omized , double-blind , placebo-controlled trial was carried out at the Diabetes Centre of Sapienza University , Rome , Italy , to assess oral treatment with cholecalciferol ( 2000 IU/day ) or placebo in T2D patients with NAFLD . The primary endpoint was reduction of hepatic fat fraction ( HFF ) measured by magnetic resonance ; as hepatic outcomes , we also investigated changes in serum transaminases , CK18-M30 , N-terminal Procollagen III Propeptide ( P3NP ) levels , and Fatty Liver Index ( FLI ) . Secondary endpoints were improvement in metabolic ( fasting glycaemia , HbA1c , lipids , HOMA-IR , HOMA-β , ADIPO-IR , body fat distribution ) and cardiovascular ( ankle-brachial index , intima-media thickness , flow-mediated dilatation ) parameters from baseline to end of treatment . Results Sixty-five patients were r and omized , 26 ( cholecalciferol ) and 29 ( placebo ) subjects completed the study . 25(OH ) vitamin D significantly increased in the active treated group ( 48.15 ± 23.7 to 89.80 ± 23.6 nmol/L , P < 0.001 ) ; however , no group differences were found in HFF , transaminases , CK18-M30 , P3NP levels or FLI after 24 weeks . Vitamin D neither changed the metabolic profile nor the cardiovascular parameters . Conclusions Oral high-dose vitamin D supplementation over 24 weeks did not improve hepatic steatosis or metabolic/cardiovascular parameters in T2D patients with NAFLD . Studies with a longer intervention period are warranted for exploring the effect of long time exposure to vitamin D.Trial registration This trial was approved on July 2011 by the Ethics Committee of Policlinico Umberto I , Sapienza University of Rome , Italy , and registered at www . clinical trialsregister.eu number 2011 - 003010 - 17 We sought to determine if vitamin D supplementation , to target 25(OH)D concentrations of 30–40 ng/mL , improves endothelial function in Singapore ’s multi-ethnic type 2 diabetes mellitus population . We r and omised 64 type 2 diabetes mellitus patients with hypovitaminosis D to cholecalciferol 4000 International Unit/matching placebo [ baseline 25(OH)D < 20 ng/mL ] or cholecalciferol 2000 International Unit/matching placebo [ baseline 25(OH)D : 20–30 ng/mL ] daily for 16 weeks with a down titration at 8 weeks if 25(OH)D > 30 ng/mL. Endothelial function was assessed by peripheral tonometry ( reactive hyperaemia index – endothelial peripheral arterial tonometry ) and vascular biomarkers : E-selectin , von-Willebr and factor and high-sensitivity C-reactive protein . We compared the change from baseline parameters in the two groups using Student ’s t-test or Kruskal – Wallis test . A log-normal multivariate regression analysis was used to adjust for relevant baseline variables . The median reactive hyperaemia index in the vitamin D group increased from 0.65 ( interquartile range : 0.42 ) to 0.73 ( interquartile range : 0.36 ) , whereas it decreased from 0.73 ( interquartile range : 0.65 ) to 0.65 ( interquartile range : 0.38 ) ( p = 0.02 ) in the placebo group . After adjustment for baseline variables , the change was not statistically significant for reactive hyperaemia index ( p = 0.07 ) and for other vascular biomarkers ( p > 0.05 ) . Targeted vitamin D supplementation for 16 weeks result ed in a small but non-significant improvement in endothelial function in a type 2 diabetes mellitus cohort Background / Aims Recent epidemiological studies revealed a striking inverse relationship between vitamin D levels , glucose intolerance/insulin resistance ( IR ) , and cardiovascular disease . However , few interventional studies have evaluated the effect of vitamin D supplementation on cardiovascular risk , such as IR and arterial stiffness , in diabetes . We investigated the role of vitamin D supplementation on cardiovascular risk in type 2 diabetes patients , including metabolic parameters , IR , and arterial stiffness . Methods We enrolled patients who were taking antidiabetic medications or managed their diabetes using lifestyle changes . We excluded patients who were taking vitamin D or calcium supplements .  We r and omized participants into the vitamin D group ( cholecalciferol 2,000 IU/day + calcium 200 mg/day , n = 40 ) or the placebo group ( calcium 200 mg/day , n = 41 ) . We compared their IR ( homeostasis model of assessment [HOMA]-IR ) and arterial stiffness ( brachial-ankle pulse wave velocity and radial augmentation index ) before and after 24 weeks of intervention . Results The baseline characteristics of the two groups were similar . A total of 62 participants ( placebo , 30 ; vitamin D , 32 ) completed the study protocol . At the end of the study period , the 25-hydroxyvitamin D [ 25(OH)D ] levels were significantly higher in the vitamin D group than in the placebo group ( 35.4 ± 8.5 ng/mL vs. 18.4 ± 7.3 ng/mL , p < 0.001 ) . There was no difference in HOMA-IR or changes in arterial stiffness  ( placebo , 21 , vitamin D , 24 ) between the groups . Conclusions Our data suggest that high-dose vitamin D supplementation might be effective in terms of elevating 25(OH)D levels . However , we identified no beneficial effects on cardiovascular risk in type 2 diabetes , including IR and arterial stiffness 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 Abstract Aims To assess whether a single parental dose of 25-hydroxy vitamin D [ 25(OH)Vit D ] could improve glucose control and inflammation in type 2 diabetic patients ( T2D ) with ischemic heart disease ( IHD ) . Methods A r and omized , placebo-controlled , double-blind trial was performed on 95 patients ( 47—placebo and 48—vitamin D groups ) . Participants were r and omized using a r and omization table to a single dose of either vitamin D ( 300,000 IU , IM ) or a matching placebo . Fasting blood sugar ( FBS ) , glycosylated hemoglobin ( HbA1c ) , 25(OH)Vit D and high-sensitivity C-reactive protein ( hs-CRP ) were measured at baseline and at 8 weeks . Results No significant differences in baseline values were noted between groups , except in HbA1c , which was lower in the placebo group . In the supplemented group , the level of serum 25(OH)Vit D increased ( 29.6 ± 20.8 vs. 44.5 ± 19.2 ng/mL ) and those of FBS and HbA1c decreased significantly [ 186.5 ± 64.1 vs. 165.1 ± 58.5 mg/dL and 8.2 ± 2.0 % ( 66.3 ± 21.8 mmol/mol ) vs. 7.7 ± 1.8 % ( 61.7 ± 20.0 mmol/mol ) , respectively ] ( all p < 0.05 ) , and no changes , however , were observed in the placebo group . We also compared change of marginal means of outcome variables ( HbA1c , FBS , 25(OH)Vit D and hs-CRP ) from baseline between the vitamin D versus placebo group , using ANCOVA , adjusted for the baseline of each variable itself , season at study entry , age and body mass index . During trial , only HbA1c level decreased significantly [ 0.48 % ( st and ard error : 0.17 ) , p = 0.04 ] . No any adverse effect was seen . Conclusions A single parenteral dose of vitamin D in T2D patients with IHD  improved glycemic control , but not inflammatory status . Clinical trial registryAustralian New Zeal and Clinical Trial Registry . Clinical trial numberACTRN12614000529640 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 : Abstract Background Recently , it has been reported that urinary angiotensinogen levels is a specific index of the intrarenal renin-angiotensin-aldosterone system ( RAAS ) status and it is significantly correlated with urinary albumin : creatinine ( Cr ) ratio in hypertensive patients . The aim of the present study was to assess the effect of activation of the Vitamin D receptor with calcitriol on albuminuria and urinary angiotensinogen as a novel biomarker of the intra-renal RAAS status in patients with diabetic nephropathy ( DN ) . Methods Ninety-eight patients with type 2 diabetes and albuminuria who were treated with RAAS inhibitors ( angiotensin-converting enzyme inhibitor ( ACE-i ) or angiotensin receptor blocker ( ARB ) ) have participated in this study . Patients were r and omized to receive either placebo ( n = 50 ) or 0.25 μg/day calcitriol ( n = 48 ) . We have examined urinary albumin : Cr ratio and urinary angiotensinogen : Cr ratio before and 24 weeks later after treatment in both group . Results The mean urinary albumin : Cr ratio and urinary angiotensinogen : Cr ratio were significantly higher in patients with DN than in normal controls ( p < 0.001 ) . Urinary angiotensinogen : Cr ratio was significantly , positively correlated with urinary albumin : Cr ratio in both groups ( in the placebo group ; p = 0.01 , r = 0.4236 , in calcitriol group ; p = 0.01 , r = 0.4564 ) . Conclusion These data indicated that administration of Vitamin D receptor activator in combination with RAAS inhibitors had an additional benefit in lowering albuminuria in patients with DN . More pronounced reduction of urinary albumin : Cr ratio that was positively correlated with angiotensinogen : Cr ratio in calcitriol group suggested that Vitamin D receptor activation might blunt albuminuria by reducing urinary angiotensinogen levels reflecting intra-renal RAAS status 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 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 CONTEXT Systemic inflammation is thought to have a central role in diabetic long-term complications . OBJECTIVE The aim of this study was to investigate the effects of vitamin D either with or without extra calcium on certain inflammatory biomarkers in the subjects with type 2 diabetes ( T2D ) . DESIGN , SETTING , AND PARTICIPANTS This was a double-blind , r and omized , controlled trial conducted over 12 wk in 90 T2D subjects aged 30 - 60 yr from both sexes . INTERVENTION Subjects were r and omly allocated to one of three groups to receive two 250-ml bottles a day of plain Persian yogurt drink or doogh ( PD , containing 150 mg calcium and no detectable vitamin D(3)/250 ml ) , vitamin D-fortified doogh ( DD , containing 500 IU vitamin D(3 ) and 150 mg calcium/250 ml ) , or calcium + vitamin D(3)-fortified doogh ( CDD , containing 500 IU vitamin D(3 ) and 250 mg calcium/250 ml ) . OUTCOME MEASURES The changes in inflammatory markers were evaluated . RESULTS Compared to the baseline values , highly sensitive C-reactive protein , IL-1β , IL-6 , fibrinogen , and retinol binding protein-4 concentrations significantly decreased in both the DD and CDD groups . Although the decrement in highly sensitive C-reactive protein and fibrinogen was more in CDD compared to DD ( -4.0 ± 8.5 vs. -1.3 ± 2.8 mg/liter , and -0.40 ± 0.74 and -0.20 ± 0.52 mg/liter , respectively ) , the differences were not significant . There was a significant increase in serum adiponectin in both the DD and CDD groups ( 51.3 ± 65.3 vs. 57.1 ± 33.8 μg/liter ; P < 0.05 ) . Mean adiponectin changes in CDD were significantly higher than in PD ( P = 0.021 ) . CONCLUSIONS Daily intake of vitamin D-fortified doogh improved inflammatory markers in T2D subjects , and extra calcium conferred additional benefit only for the antiinflammatory adipokine , i.e. adiponectin 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 The aim of this study was to assess the effects of single oral bolus of 300,000 IU Vitamin D3 on serum levels and on bone and metabolic parameters in diabetic patients . This study is a Phase IV , r and omized , double-blind , placebo-controlled , monocenter clinical trial . Thirty patients , 60 years or older , with type 2 diabetes mellitus , and diabetic foot complications , were enrolled and monitored for 24 weeks : 14 were treated with Vitamin D3 and 16 with placebo . Parameters including glucose , adiponectin , leptin , osteoprotegerin ( OPG ) , 25-hydroxyvitamin D [ 25(OH)D ] , beta-CrossLaps , osteocalcin , bone-specific isoenzyme of alkaline phosphatase , tumor necrosis factor-α and parathyroid hormone were measured at screening and baseline and 12 and 24 weeks after treatment . Analysis of covariance was used to compare treatment groups . Analysis of the data detected a significant increase in 25(OH)D serum levels both at 12 and 24 weeks with respect to baseline values only in the treated patients . Significant variations with respect to baseline values were noted in OPG ( P = 0.0085 ) and in leptin ( P = 0.0442 ) levels : these were lower in the placebo group at week 24 but higher in the treated group . Vitamin D3 supplementation significantly increased serum leptin and OPG levels . Further , large-scale clinical trials are warranted to confirm these results CONTEXT To the best of our knowledge , no study has examined the effects of vitamin D-calcium cosupplementation on inflammatory biomarkers and adipocytokines in vitamin D-insufficient type 2 diabetics . OBJECTIVE This study was performed to assess the effects of vitamin D and calcium supplementation on inflammatory biomarkers and adipocytokines in vitamin D-insufficient people with type 2 diabetes . METHODS Totally , 118 diabetic patients were enrolled in this r and omized , placebo-controlled clinical trial . After matching for age , sex , body mass index , type and dose of hypoglycemic agents , and duration of diabetes , subjects were r and omly assigned into 4 groups receiving the following : 1 ) 50000 IU/wk vitamin D + calcium placebo ; 2 ) 1000 mg/d calcium + vitamin D placebo ; 3 ) 50 000 IU/wk vitamin D + 1000 mg/d calcium ; or 4 ) vitamin D placebo + calcium placebo for 8 weeks . Blood sampling was done for the quantification of inflammatory biomarkers and adipocytokines at the study baseline and after 8 weeks of intervention . RESULTS Calcium ( changes from baseline : -75 ± 19 ng/ml , P = .01 ) and vitamin D alone ( -56 ± 19 ng/mL , P = .01 ) and joint calcium-vitamin D supplementation ( -92 ± 19 ng/mL , P = .01 ) result ed in a significant reduction in serum leptin levels compared with placebo ( -9 ± 18 ng/mL ) . This was also the case for serum IL-6 , such that calcium ( -2 ± 1 pg/mL , P < .001 ) and vitamin D alone ( -4 ± 1 pg/mL , P < .001 ) and their combination ( -4 ± 1 pg/mL , P < .001 ) led to significant reductions compared with placebo ( 3 ± 1 pg/mL ) . After adjustment for potential confounders , individuals in the calcium ( -3.1 ± 1.3 , P < .05 ) , vitamin D ( -3.1 ± 1.3 , P < .05 ) , and joint calcium-vitamin D groups ( -3.4 ± 1.3 , P < .05 ) had greater reductions in serum TNF-α concentrations compared with placebo ( 0.1 ± 1.2 ) . Individuals who received joint calcium-vitamin D supplements tended to have a decrease in serum high-sensitivity C-reactive protein levels compared with placebo after controlling for baseline levels ( -1.14 ± 0.25 vs 0.02 ± 0.24 ng/mL , P = .09 ) . CONCLUSION Joint calcium-vitamin D supplementation might improve systemic inflammation through decreasing IL-6 and TNF-α concentrations in vitamin D-insufficient people with type 2 diabetes 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 Background : Since tumor necrosis factor-α ( TNF-α ) could be one of the risk factors at the development of diabetes complications ; as well as serum leptin deficiency is related to increased susceptibility to infections in diabetic patients , they are potential indices from the preventive medicine viewpoint . This study was conducted to represent the effect of supplemental vitamin D3 on serum leptin , TNF-α and adiposity in type 2 diabetic patients . Methods : In this r and omized double-blind placebo-controlled trial , study sample was selected through type 2 diabetic patients ( n = 51 ) . A total of 26 patients were orally supplemented by vitamin D3 ( 400 IU/d ) ( vitamin D group ) and 25 patients by placebo ( placebo group ) for 14 weeks . The blood glycated hemoglobin ( HbA1c ) and the serum ionized Ca , leptin , TNF-α , and serum 25-hydroxyvitamin D ( 25[OH ] D ) were measured at the two groups in the baseline and postintervention stages . Results : It was shown that despite of theplacebo group , serum 25(OH ) D and serum leptin was significantly increased ( P = 0.001 and P = 0.002 , respectively ) , while serum TNF-α was decreased significantly ( P = 0.001 ) in vitamin D group . The remaining parameters , including body fat mass and HbA1c had no alterations between baseline and postintervention stages in vitamin D group . Conclusions : This study may advocate vitamin D supplementation among type 2 diabetic patients due to its beneficial effects on prevention of diabetes complications AIM Diabetes and vitamin D deficiency are widely prevalent in India . Studies have proven correlation between low vitamin D levels and pulmonary tuberculosis ( PTB ) and low vitamin D levels and insulin resistance . We evaluated the effects of vitamin D supplementation on type 2 diabetes mellitus patients with pulmonary tuberculosis ( PTB ) . METHODS Forty-five subjects ( M : F=34:11 ) were screened . Inclusion criteria were age > 15 years , newly diagnosed PTB cases with uncontrolled diabetes , serum vitamin D<20 ng/ml . The patients with vitamin D level<20 ng/ml were r and omly assigned to 2 groups . Group 1 subjects received oral cholecalceferol ( 60,000 units/week ) and calcium carbonate ( 1g/day ) along with anti tubercular treatment ( ATT ) , while group 2 subjects did not .  Sputum was checked at interval of 2 weeks for 12 weeks . Primary end point was time to achieve sputum smear conversion . RESULTS Fifteen patients having vitamin D>20 ng/ml were excluded . Age of the patients was 42.9±13.2 years and serum vitamin D levels were 18.4±15.3 ng/ml . Sputum smear conversion was 6 weeks in group 1 versus 8 weeks in group 2 ( p=0.067 ) . Glycated hemoglobin levels reduced from 11.1±1.3 to 7.7±0.9 in group 1 versus 10.3±1.2 to 7.8±1.1 ( p>0.1 ) . CONCLUSION Vitamin D can serve as adjuvant treatment of tuberculosis in diabetics with vitamin D deficiency . Further studies are required to vali date this observation and define a cut off for vitamin D level to prevent immunological alterations Objective . Systemic lupus erythematosus ( SLE ) is a chronic multisystem inflammatory autoimmune disease . Vitamin D has potent immunomodulatory properties that support its use in the treatment of autoimmune conditions , including SLE . We assessed vitamin D status in patients with SLE and determined alterations in inflammatory and hemostatic markers and disease activity before and after vitamin D supplementation . Methods . Patients with SLE ( n = 267 ) were r and omized 2:1 to receive either oral cholecalciferol 2000 IU/day or placebo for 12 months . Outcome measures included assessment of alterations in levels of proinflammatory cytokines and hemostatic markers , and improvement in disease activity before and after 12 months of supplementation . Disease activity was measured by the SLE Disease Activity Index . Vitamin D levels were measured by Liaison immunoassay ( normal 30–100 ng/ml ) . Serum levels between 10 and 30 ng/ml were classified as vitamin D insufficiency and levels < 10 ng/ml as vitamin D deficiency . Results . The mean 25(OH)D level at baseline was 19.8 ng/ml in patients compared to 28.7 ng/ml in controls . The overall prevalence of suboptimal and deficient 25(OH)D serum levels among patients with SLE at baseline was 69 % and 39 % , respectively . Lower 25(OH)D levels correlated significantly with higher SLE disease activity . At 12 months of therapy , there was a significant improvement in levels of inflammatory and hemostatic markers as well as disease activity in the treatment group compared to the placebo group . Conclusion . Vitamin D supplementation in patients with SLE is recommended because increased vitamin D levels seem to ameliorate inflammatory and hemostatic markers and show a tendency toward subsequent clinical improvement . Clinical Trial Registry NCT01425775 BACKGROUND & AIMS Vitamin D supplementation has the potential to alleviate the cardiovascular damage in diabetic patients . The present study was design ed to evaluate long term impact of high doses of vitamin D on arterial properties , glucose homeostasis , adiponectin and leptin in patients with type 2 diabetes mellitus . METHODS AND RESULTS In r and omized , placebo-controlled study 47 diabetic patients were assigned into two groups : Group 1 received oral daily supplementation with vitamin D at a dose of 1000 U/day for 12 months . Group 2 received matching placebo capsules . Blood sampling for metabolic parameters , including fasting glucose , lipid profile , HbA1C , insulin , hs-CRP , 25 OH Vit D , adiponectin and leptin was performed at baseline and at the end of the study . Insulin resistance was assessed by homeostasis model assessment ( HOMA-IR ) . Central aortic augmentation index ( AI ) was evaluated using SphygmoCor . RESULTS The two groups were similar at baseline in terms of hemodynamic parameters . After 12 months , AI decreased significantly during the treatment period in patients received vitamin D ( p < 0.0001 ) and did not change in placebo group . Glucose homeostasis parameters , leptin as well as leptin adiponectin ratio did not change in both groups . 25 OH Vit D level significantly increased ( p = 0.022 ) and circulating adiponectin marginally increased ( p = 0.065 ) during 12 month treatment period in active treatment and did not change in placebo group . CONCLUSIONS High doses of  vitamin D supplementation in diabetic patients was associated with significant decrease in AI during one year treatment . This beneficial vascular effect was not associated with improvement in glucose homeostasis parameters BACKGROUND Epidemiological studies suggest a higher prevalence of metabolic syndrome and its components among individuals with vitamin D deficiency . The aim of the present study was to determine whether vitamin D treatment  improves glucose control and insulin sensitivity in Type 2 diabetes mellitus ( T2DM ) . METHODS Subjects with T2DM and serum 25-hydroxyvitamin D ( 25(OH)D ) concentrations < 25 ng/mL were r and omized to receive 400 IU ( Group 1 ) or 1200 IU ( Group 2 ) cholecalciferol for 4 months . Fasting plasma glucose , glycosylated hemoglobin ( HbA1c ) , Quantitative Insulin Sensitivity Check Index ( QUICKI ) , serum lipid levels and serum adiponectin were measured at baseline and at 4 months . RESULTS Mean 25(OH)D levels increased in both groups ( from 17.6±1.5 to 25.5±1.8 ng/mL in Group 1 and from 15.6±1.4 to 27.4±2.4 ng/mL in Group 2 ; P≤0.001 vs baseline for each group ) . No significant differences were noted in fasting plasma glucose , HbA1c , QUICKI , serum adiponectin , and lipid levels compared with baseline within groups or between the two groups . CONCLUSIONS In the present pilot study , conventional vitamin D treatment at a level improving , but not optimizing , serum 25(OH)D did not improve glycemia , insulin sensitivity , or lipid profile . However , diabetes and lipids were relatively well controlled at baseline . Future studies should be design ed to achieve optimal concentrations of serum 25(OH)D ( at least > 32 ng/mL ) and should include subjects showing more abnormal parameters of glycemia , lipid , and insulin sensitivity at baseline Background / Objectives : The aim was to examine the causal effect of vitamin D on serum adiponectin using a multiple instrument Mendelian r and omization approach . Subjects/ Methods :  Serum 25-hydroxy vitamin D ( 25(OH)D ) and serum total or high molecular weight ( HMW ) adiponectin  were measured in two Danish population -based studies : the Inter99 study ( 6405 adults , 30–60 years ) conducted in 1999–2001 , and the MONICA10 study ( 2656 adults , 41–71 years ) conducted in 1993–1994 . Results : In the Inter99 study , serum 25(OH)D was positively associated with total adiponectin ( the effect estimate in % per doubling of 25(OH)D was 4.78 , 95 % CI : 1.96 , 7.68 , P<0.001 ) . Using variations in the vitamin D-binding protein gene and the filaggrin gene as instrumental variables , the causal effect in % was estimated to 61.46 , 95 % CI : 17.51 , 120.28 , P=0.003 higher adiponectin per doubling of 25(OH)D. In the MONICA10 cohort , no significant association was observed between the serum concentrations of 25(OH)D and HMW adiponectin ( the effect estimate in % per doubling of 25(OH)D was −1.51 , 95 % CI : −5.80 , 2.98 , P=0.50 ) , although the instrumental variables analysis to some extent supported a positive causal association ( the effect estimate in % per doubling of 25(OH)D was 37.13 , 95 % CI : −3.67 , 95.20 , P=0.080 ) . Conclusions : The results indicate a possible causal association between serum 25(OH)D and total adiponectin . However , the association was not replicated for HMW adiponectin . Thus , further studies are needed to confirm a causal relationship
target: Conclusions This meta‐ analysis provides level 1 evidence that vitamin D supplementation may reduce chronic low‐ grade inflammation in patients with type 2 diabetes .
background: Background Vitamin D has been proposed to have anti‐inflammatory properties ; however , the effect of vitamin D supplementation on inflammation in type 2 diabetes has not been established .
  Objective The aim of this systematic review and meta‐ analysis was to examine the effect of vitamin D supplementation on inflammatory markers in patients with type 2 diabetes and to identify relevant gaps in knowledge .