title: Vitamin D supplementation in obese type 2 diabetes subjects in Ajman, UAE: a randomized controlled double-blinded clinical trial Biases in Randomized Trials: A Conversation Between Trialists and Epidemiologists. 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 The effects of vitamin D and omega-3 fatty acids co-supplementation on biomarkers of inflammation, oxidative stress and pregnancy outcomes in patients with gestational diabetes The effect of high-dose vitamin D supplementation on insulin resistance and arterial stiffness in patients with type 2 diabetes The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Improvements in peripheral vascular function with vitamin D treatment in deficient adolescents with type 1 diabetes 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 Vitamin D attenuates pro-inflammatory TNF-α cytokine expression by inhibiting NF-кB/p65 signaling in hypertrophied rat hearts 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. The effect of calcitriol on lipid profile and oxidative stress in hyperlipidemic patients with type 2 diabetes mellitus Effect of various doses of vitamin D supplementation on pregnant women with gestational diabetes mellitus: A randomized controlled trial. The effects of calcitriol with calcium carbonate supplementation on inflammatory biomarkers in chronic kidney disease patients’ with low vitamin D The effects of vitamin D on severity of coronary artery atherosclerosis and lipid profile of cardiac patients Vitamin D and inflammatory markers: cross-sectional analyses using data from the English Longitudinal Study of Ageing (ELSA) Daily intake of vitamin D- or calcium-vitamin D-fortified Persian yogurt drink (doogh) attenuates diabetes-induced oxidative stress: evidence for antioxidative properties of vitamin D. Effects of calcium–vitamin D co-supplementation on glycaemic control, inflammation and oxidative stress in gestational diabetes: a randomised placebo-controlled trial 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. Effect of high doses of vitamin D on arterial properties, adiponectin, leptin and glucose homeostasis in type 2 diabetic patients. Effect of vitamin D supplementation on inflammation and nuclear factor kappa-B activity in overweight/obese adults: a randomized placebo-controlled trial
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 Trialists and epidemiologists often employ different terminology to refer to biases in r and omized trials and observational studies , even though many biases have a similar structure in both types of study . We use causal diagrams to represent the structure of biases , as described by Cochrane for r and omized trials , and provide a translation to the usual epidemiologic terms of confounding , selection bias , and measurement bias . This structural approach clarifies that an explicit description of the inferential goal -the intention-to-treat effect or the per- protocol effect-is necessary to assess risk of bias in the estimates . Being aware of each other 's terminologies will enhance communication between trialists and epidemiologists when considering key concepts and methods for causal inference 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 Background This study was carried out to determine the effects of vitamin D and omega-3 fatty acids co- supplementation on biomarkers of inflammation , oxidative stress and pregnancy outcomes  in gestational diabetes ( GDM ) patients . Methods This r and omized , double-blind , placebo-controlled trial was conducted among 120 GDM women . Participants were r and omly divided into four groups to receive : 1 ) 1000 mg omega-3 fatty acids containing 180 mg eicosapentaenoic acid ( EPA ) and 120 mg docosahexaenoic acid ( DHA ) twice a day + vitamin D placebo ( n = 30 ) ; 2 ) 50,000 IU vitamin D every 2 weeks + omega-3 fatty acids placebo ( n = 30 ) ; 3 ) 50,000 IU vitamin D every 2 weeks + 1000 mg omega-3 fatty acids twice a day ( n = 30 ) and 4 ) vitamin D placebo + omega-3 fatty acids placebo ( n = 30 ) for 6 weeks . Results Subjects who received vitamin D plus omega-3 fatty acids supplements compared with vitamin D , omega-3 fatty acids and placebo had significantly decreased high-sensitivity C-reactive protein ( −2.0 ± 3.3 vs. -0.8 ± 4.4 , −1.3 ± 2.4 and + 0.9 ± 2.7 mg/L , respectively , P = 0.008 ) , malondialdehyde ( −0.5 ± 0.5 vs. −0.2 ± 0.5 , −0.3 ± 0.9 and + 0.5 ± 1.4 μmol/L , respectively , P < 0.001 ) , and increased total antioxidant capacity ( + 92.1 ± 70.1 vs. + 55.1 ± 123.6 , + 88.4 ± 95.2 and + 1.0 ± 90.8 mmol/L , respectively , P = 0.001 ) and glutathione ( + 95.7 ± 86.7 vs. + 23.0 ± 62.3 , + 30.0 ± 66.5 and −7.8 ± 126.5 μmol/L , respectively , P = 0.001 ) . In addition , vitamin D and omega-3 fatty acids co-supplementation , compared with vitamin D , omega-3 fatty acids and placebo , result ed in lower incidences of newborns ’ hyperbilirubinemiain ( P = 0.037 ) and newborns ’ hospitalization ( P = 0.037 ) . Conclusion Overall , vitamin D and omega-3 fatty acids co-supplementation for 6 weeks among GDM women had beneficial effects on some biomarkers of inflammation , oxidative stress and pregnancy outcomes 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 Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND Vitamin D ( VitD ) deficiency is prevalent in adolescents with type 1 diabetes ( T1D ) and is associated with diabetes-related vascular complications in adulthood . The objective of this clinical trial was to assess VitD treatment on endothelial function ( EF ) and markers of renal inflammation , in this patient group . METHODS Adolescents with T1D with suboptimal levels of VitD ( < 37.5 nmol/L ) were treated for 12 to 24 weeks with a VitD analog ( VitD3 ) at doses of 1000 or 2000 IU daily . The primary end-point assessed the change in reactive hyperemia index ( lnRHI ) , a measure of EF . Secondary end-points included changes in blood pressure , lipid profile , HbA1c and albumin creatinine ratio ( ACR ) . Urinary cytokine/chemokine inflammatory profile was also assessed in a subset of subjects posttreatment . RESULTS Two hundred and seventy-one subjects were screened for VitD status and 31 VitD deficient subjects with a mean age of 15.7 ± 1.4 years were enrolled and completed the study . Mean 25-OH-VitD levels significantly increased ( 33.0 ± 12.8 vs 67.0 ± 23.2 nmol/L , P < .01 ) with a significant improvement in EF  following VitD supplementation ( lnRHI 0.58 ± 0.20 vs 0.68 ± 0.21 , P = .03 ) . VitD supplementation did not significantly impact systolic blood pressure/diastolic blood pressure ( SBP/DBP ) , lipids , HbA1c and ACR and no adverse effects were seen . Several urinary inflammatory cytokines/chemokines : MCP-3 ( P < .01 ) , epidermal growth factor ( EGF ) ( P < .01 ) tumor necrosis factor β ( TNFβ ) ( P = .01 ) , interleukin-10 ( IL-10 ) ( P = .01 ) , also significantly decreased post-VitD-treatment . CONCLUSIONS Treatment with VitD was associated with an improvement in EF and reduced expression of urinary inflammatory markers in adolescents with T1D . This data is suggestive of an additional benefit of VitD supplementation on early markers of microvascular complications 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 A growing body of evidence suggests that immune activation and inflammatory mediators may play a key role in the development and progression of left ventricle ( LV ) hypertrophy . The present study was design ed to test the hypothesis that the cardioprotective effect of cholecalciferol ( Vit-D3 ) is mediated via the regulation of messenger RNA ( mRNA ) expression of pro-inflammatory cytokines . Rats were r and omly divided into four groups : control group received normal saline ( 0.9 % NaCl ) i.p . for 14 days ; Vit-D3 group received Vit-D3 at a dose of 12 μg/kg/day by gavage for 14 days ; ISO group received saline for 7 days , and at day 7 , ISO ( 5 mg/kg/day ) was injected i.p . for 7 consecutive days to induce cardiac hypertrophy ; and Vit-D3 + ISO group was treated with Vit-D3 for 14 days , and at day 7 , ISO was administered for 7 consecutive days . Heart/body weight ratio , troponin-T , creatine kinase-MB , and tumor necrosis factor-α ( TNF-α ) levels of LV tissue were estimated . Levels of mRNA expression of NF-кB (NF-кB)/p65 and inhibitory kappa B (IкB)-α were determined by real-time PCR . Vit-D3 administration before and during induction of cardiac hypertrophy significantly reduced ( P < 0.001 ) cardiac biomarkers . The histopathological examination further confirmed these results . In addition , Vit-D3 significantly decreased ( P < 0.001 ) NF-кB-p65 mRNA expression and increased ( P < 0.01 ) IкB-α mRNA expression in LV tissues compared to ISO group . Based on these findings , it was concluded that the administration of cholecalciferol markedly attenuated the development of ISO-induced cardiac hypertrophy likely through downregulation of TNF-α /NF-кb/p65 signaling pathways . However , it should be pointed out that other signaling pathways may contribute to the cardioprotective effect of Vit-D3 which requires further investigation 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 Cardiovascular mortality is high among diabetic patients due to abnormalities in the plasma lipid and lipoprotein metabolism , and increased oxidative stress . This study aim ed to investigate the effects of active vitamin D on serum lipids and oxidative stress markers in type 2 diabetic patients . METHODS A double-blind r and omized placebo-controlled trial was carried out in 70 participants with type 2 diabetes , aged 30 - 75 years of age . The participants were r and omly assigned to two groups . One group received two capsules of calcitriol ( 0.25 µg 1,25-dihydroxycholecalciferol per capsule ) per day . The second group received placebo tablets . All participants received their oral hypoglycemic drugs as prescribed by the endocrinologist . At the beginning , after 6 weeks , and at the end of the 12-week supplementation trial , serum total cholesterol , low-density lipoprotein ( LDL ) , high-density lipoprotein ( HDL ) , triglyceride ( TG ) , and serum malondialdehyde ( MDA ) levels were measured . RESULTS There was a significant reduction in total cholesterol , LDL-cholesterol , TG , and MDA levels in both treatment and placebo groups ( P < 0.05 ) . Serum HDL-cholesterol level decreased significantly in the placebo group ( P < 0.05 ) , while it remained unchanged in the treatment group . However , the P values related to the between group ’s comparisons were not significant for any variables . CONCLUSION Active vitamin D  reduced lipid profile and oxidative stress markers in diabetic patients compared to the control group , but these alterations were not statistically It has previously been reported that the influence of vitamin D on the metabolism of calcium and phosphorus is associated with diabetes , cardiovascular disease , Alzheimer 's disease , cancer and other systemic diseases , and is considered an important indicator of general health . The present study was conducted to determine the effect of various doses of vitamin D supplementation on glucose metabolism , lipid concentrations , inflammation and the levels of oxidative stress of pregnant women with gestational diabetes mellitus ( GDM ) . The present r and omized , double-blind placebo-controlled clinical trial was conducted on 133 pregnant women with GDM during weeks 24 - 28 of pregnancy . The patients were r and omly divided into four groups . The control group ( n=20 ) received a placebo ( sucrose ; one granule/day ) , the low dosage group ( n=38 ) received the daily recommended intake of 200 IU vitamin D ( calciferol ) daily , the medium dosage group ( n=38 ) received 50,000 IU monthly ( 2,000 IU daily for 25 days ) and the high dosage group ( n=37 ) received 50,000 IU every 2 weeks ( 4,000 IU daily for 12.5 days ) . The general characteristics and dietary intakes of the patients with GDM were similar between each group . Using ELISA kits , it was determined that insulin , homeostatic model assessment -insulin resistance and total cholesterol were significantly reduced by high dosage vitamin D supplementation ( P<0.05 ) . Total antioxidant capacity and total glutathione levels were significantly elevated as a result of high dosage vitamin D supplementation ( P<0.01 ) . In conclusion , high-dose vitamin D supplementation ( 50,000 IU every 2 weeks ) significantly improved insulin resistance in pregnant women with GDM Introduction Chronic kidney disease ( CKD ) patients ’ are at risk of low vitamin D and chronic inflammation . We studied the effect of 12 weeks calcitriol and calcium carbonate supplementation on inflammatory mediators serum ; interleukin-6 ( IL-6 ) , interleukin-10 ( IL-10 ) and highly sensitive C-reactive protein ( hs-CRP ) . Material and methods A prospect i ve r and omized study in CKD stages 2 - 4 with serum 25-hydroxyvitamin D ( 25-OHD ) levels < 30 ng/ml . Patients were r and omized into the Vitamin D + Calcium ( Vitamin D + C ) or Calcium group . Serums were analyzed at baseline , week 6 and 12 . Results Fifty patients , median age of 53 ( 13.5 ) years were recruited . Their median IL-10 was 13.35 ( 25.22 ) pg/ml . At week 12 , serum IL-6 was reduced in both groups ( p = 0.001 ) , serum IL-10 was maintained in the Vitamin D + C group ( p = 0.06 ) and was reduced in the Calcium group ( p = 0.001 ) . CKD-diabetic patients had reduced serum IL-6 in both study groups ( p = 0.001 ) and a reduction was seen in the Vitamin D + C group of the non-diabetics counterparts ( p = 0.005 ) . Serum IL-10 was reduced in the Calcium group ( p < 0.05 ) whereas serum 25-OHD rose in both groups , regardless of their diabetic status ( p < 0.05 ) . Conclusions Twelve weeks , calcitriol supplementation maintained IL-10 , had no effects on hs- CRP and had no additional benefit compared to calcium carbonate in reducing serum IL-6 except in non-diabetics Introduction A deficiency of 25-hydroxyvitamin D ( 25(OH)D ) ( the st and ard biomarker for vitamin D status ) can have multiple impacts on the cardiovascular system . The aim of the study was to assess of the influence of 25(OH)D on severity of coronary atherosclerosis and lipid profile . Material and methods The study involved prospect ively 637 patients subject to coronary catheterization . The stage of coronary atherosclerosis was assessed using the Coronary Artery Surgery Study score ( CASSS ) . Plasma concentration of 25(OH)D  was measured using an electrochemiluminescent immunoassay . The levels of total cholesterol ( TC ) , high-density cholesterol ( HDL-C ) and triglycerides ( TG ) were measured using the enzymatic method , and the concentration of low-density cholesterol ( LDL-C ) was calculated with the Friedewald equation . Results The average level of 25(OH)D was 15.85 ng/ml . A higher level of 25(OH)D was observed in men ( 16.28 ng/ml vs. 15.1 ng/ml ; p = 0.027 ) . The study did not reveal any significant correlation between the level of 25(OH)D and severity of coronary atherosclerosis . It was observed however that the increase of 25(OH)D level results in an increased number of patients without significant lesions in the coronary arteries . In the whole group of women and men in the age group of 70–80 years an inverse relationship was observed between the level of 25(OH ) and the severity of coronary atherosclerosis . The whole study group showed a statistically significant inverse correlation of the 25(OH)D level with TC ( p = 0.0057 ) , LDL-C ( p = 0.00037 ) and TG ( p = 0.00017 ) . Conclusions Women and men over 70 years showed an inverse correlation of the 25(OH)D level and the stage of coronary atherosclerosis . Deficiency of 25(OH)D affects the levels of TC , LDL-C and TG Recent evidence suggests that low vitamin D concentrations are associated with increased levels of inflammatory markers . However , there are limited studies investigating associations between vitamin D levels and inflammatory markers in the general population and much of this evidence in older adults is inconclusive . Therefore , this study investigates the cross-sectional association of  serum 25-hydroxyvitamin D ( 25(OH)D ) levels with inflammatory markers in 5870 older English adults from wave 6 ( 2012–2013 ) of the English Longitudinal Study of Ageing ( ELSA ) . ELSA is a large prospect i ve observational study of community-dwelling people aged 50 years and over in Engl and . Serum 25(OH)D levels , C-reactive protein ( CRP ) levels , plasma fibrinogen levels , white blood cell count ( WBC ) , age , season of blood collection , waist circumference , total non-pension household wealth , measures of health and health behaviours that included depression , number of cardiovascular , non-cardiovascular conditions and difficulties in activities of daily living , smoking , and physical activity were measured . There was a significant negative association between low 25(OH)D levels ( ≤30 nmol/l ) and CRP ( OR 1·23 , 95 % CI 1·00 , 1·51 ) and WBC ( OR 1·35 , 95 % CI 1·13 , 1·60 ) that remained after adjustment for a wide range of covariates of clinical significance . However , for fibrinogen , the association did not remain significant when waist circumference was entered in the final model . Our findings showed that 25(OH)D levels were associated with two out the three inflammatory markers investigated . The independent and inverse association between serum 25(OH)D levels and inflammation suggests a potential anti-inflammatory role for vitamin D in older English individuals from the general population BACKGROUND Both poor vitamin D status and oxidative stress ( OS ) have been independently associated with late diabetic complications , including cardiovascular disease ( CVD ) . The present study aim ed to examine the effect of daily intake of vitamin D alone or in combination with calcium as a fortified Persian yogurt drink ( doogh ) on OS over 12 weeks . METHODS Ninety patients with type 2 diabetes aged 30 - 50 years from both sexes were r and omly allocated to one of the three groups to receive two 250-mL bottles of doogh a day , which was either plain ( PD ; containing 150 mg per 250 mL of calcium and no detectable vitamin D ) , vitamin D-fortified ( DD ; containing 150 mg of calcium + 500 IU vitamin D per 250 mL ) or calcium-vitamin D-fortified ( CDD ; 250 mg od calcium + 500 IU vitamin D per 250 mL ) . RESULTS Although mean ( SD ) serum concentrations of protein carbonyl significantly decreased in both DD and CDD groups [ -2.07 ( 4.39 ) nm , P = 0.015 and -4.4 ( 7.64 ) nm , P = 0.003 , respectively ] , the change in PD group was not significant [ -0.54 ( 6.96 ) nm , P = 0.674 ] . A similar pattern was observed for cardiac myeloperoxidase [ PD : -19.4 ( 75.9 ) μg L(-1 ) , P = 0.173 ; DD : -21.8 ( 54.2 ) μg L(-1 ) , P = 0.035 , CDD : -48.5 ( 76.9 ) μg L(-1 ) , P = 0.002 ] . Superoxide dismutase increased significantly only in DD and CDD [ 56.9 ( 74.0 ) U L(-1 ) , P < 0.001 and 51.6 ( 119.9 ) U L(-1 ) , P = 0.025 , respectively ] . Changes of serum advanced glycation end-products showed a significant between-group difference among PD , DD and CDD [ 239.4 ( 388.4 ) U L(-1 ) , -58.1 ( 147.6 ) U L(-1 ) and -143.7 ( 475.9 ) U L(-1 ) × 10(3 ) , respectively , P = 0.003 ] , which remained significant after controlling for changes of fasting serum glucose ( P = 0.013 ) and glycated haemoglobin ( P = 0.015 ) . CONCLUSIONS The findings of the present study demonstrated an OS attenuating effect of vitamin D. However , extra calcium did not convey additional benefit Aims /hypothesisThis study was design ed to assess the effects of calcium and vitamin D supplementation on the metabolic status of pregnant women with gestational diabetes mellitus ( GDM ) . Methods This r and omised placebo-controlled trial was performed at maternity clinics affiliated to Kashan University of Medical Sciences , Kashan , Iran . Participants were 56 women with GDM at 24–28 weeks ’ gestation ( 18 to 40 years of age ) . Subjects were r and omly assigned to receive calcium plus vitamin D supplements or placebo . All study participants were blinded to group assignment . Individuals in the calcium – vitamin D group ( n = 28 ) received 1,000 mg calcium per day and a 50,000 U vitamin D3 pearl twice during the study ( at study baseline and on day 21 of the intervention ) , and those in the placebo group ( n = 28 ) received two placebos at the mentioned times . Fasting blood sample s were taken at study baseline and after 6 weeks of intervention . Results The study was completed by 51 participants ( calcium – vitamin D n = 25 ,  placebo n = 26 ) . However , as the analysis was based on an intention-to-treat approach , all 56 women with GDM ( 28 in each group ) were included in the final analysis . After the administration of calcium plus vitamin D supplements , we observed a significant reduction in fasting plasma glucose ( −0.89 ± 0.69 vs + 0.26 ± 0.92 mmol/l , p < 0.001 ) , serum insulin levels ( −13.55 ± 35.25 vs + 9.17 ± 38.50 pmol/l , p = 0.02 ) and HOMA-IR ( −0.91 ± 1.18 vs + 0.63 ± 2.01 , p = 0.001 ) and a significant increase in QUICKI ( + 0.02 ± 0.03 vs −0.002 ± 0.02 , p = 0.003 ) compared with placebo . In addition , a significant reduction in serum LDL-cholesterol ( −0.23 ± 0.79 vs + 0.26 ± 0.74 mmol/l , p = 0.02 ) and total cholesterol : HDL-cholesterol ratio ( −0.49 ± 1.09 vs + 0.18 ± 0.37 , p = 0.003 ) and a significant elevation in HDL-cholesterol levels ( + 0.15 ± 0.25 vs −0.02 ± 0.24 mmol/l , p = 0.01 ) was seen after intervention in the calcium – vitamin D group compared with placebo . In addition , calcium plus vitamin D supplementation result ed in a significant increase in GSH ( + 51.14 ± 131.64 vs −47.27 ± 203.63 μmol/l , p = 0.03 ) and prevented a rise in MDA levels ( + 0.06 ± 0.66 vs + 0.93 ± 2.00 μmol/l , p = 0.03 ) compared with placebo . Conclusions /interpretationCalcium plus vitamin D supplementation in women with GDM had beneficial effects on their metabolic profile . Trial registration www.i rct .ir I RCT 201311205623N11 Funding The study was supported by a grant ( no. 92110 ) from Kashan University of Medical Sciences 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 & 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 In-vitro studies suggest that vitamin D reduces inflammation by inhibiting nuclear factor kappa-B ( NFκB ) activity . Yet , no trials have examined the effects of vitamin D supplementation on NFκB activity in-vivo in humans . We conducted a double-blind r and omized trial ( RCT ) examining effects of vitamin D supplementation on inflammatory markers and NFκB activity in peripheral blood mononuclear cells ( P BMC s ) . Sixty-five overweight/obese , vitamin D-deficient ( 25-hydroxyvitamin D [ 25(OH)D ] ≤ 50 nmol/L ) adults were r and omized to a single 100,000 IU bolus followed by 4,000 IU daily cholecalciferol or matching placebo for 16 weeks . We measured BMI , % body fat , serum 25(OH)D , high-sensitivity C-reactive protein ( hsCRP ) , tumour necrosis factor ( TNF ) , monocyte chemoattractant protein-1 ( MCP-1 ) , interferon-gamma ( IFN-γ ) , several interleukins , and NFκB activity in P BMC s. Fifty-four participants completed the study . Serum 25(OH)D concentrations  increased with vitamin D supplementation compared to placebo ( p < 0.001 ) . Vitamin D and placebo groups did not differ in any inflammatory markers or NFκB activity ( all p > 0.05 ) . Results remained non-significant after adjustment for age , sex , and % body fat , and after further adjustment for sun exposure , physical activity , and dietary vitamin D intake . Although in-vitro studies report anti-inflammatory effects  of vitamin D , our RCT data show no effect of vitamin D supplementation on inflammatory markers or NFκB activity in-vivo in humans
target: Overall , this meta- analysis shows that in diabetic patients , taking vitamin D had significant effects on hs-CRP and MDA levels , and significantly increased NO , TAC and GSH levels
background: In this systematic review and meta- analysis of r and omized controlled trials ( RCTs ) , the effects of vitamin D supplementation on biomarkers of inflammation and oxidative stress in diabetic patients are summarized .