Effects of insulin lispro and chronic vitamin C therapy on postprandial lipaemia, oxidative stress and endothelial function in patients with type 2 diabetes mellitus. Association of low serum 25-hydroxyvitamin D levels and high arterial blood pressure in the elderly. A systematic review protocol examining the effect of vitamin D supplementation on endothelial function Maternal Pre-Pregnancy Obesity Is Associated with Altered Placental Transcriptome YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor‐2 tyrosine kinase with potent activity in vitro and in vivo Dietary salt restriction increases vascular insulin resistance Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes. Plasma osteoprotegerin is associated with mortality in hemodialysis patients. Calcium and vitamin D supplementation maintains parathyroid hormone and improves bone density during initial military training: a randomized, double-blind, placebo controlled trial. Topical Insulin Accelerates Wound Healing in Diabetes by Enhancing the AKT and ERK Pathways: A Double-Blind Placebo-Controlled Clinical Trial Effects of vildagliptin on postprandial markers of bone resorption and calcium homeostasis in recently diagnosed, well-controlled type 2 diabetes patients. Impact of Vitamin D Supplementation on Arterial Vasomotion, Stiffness and Endothelial Biomarkers in Chronic Kidney Disease Patients Effects of Combined Calcium and Vitamin D Supplementation on Insulin Secretion, Insulin Sensitivity and β-Cell Function in Multi-Ethnic Vitamin D-Deficient Adults at Risk for Type 2 Diabetes: A Pilot Randomized, Placebo-Controlled Trial Improvements in peripheral vascular function with vitamin D treatment in deficient adolescents with type 1 diabetes Comparison of sevelamer and calcium carbonate on endothelial function and inflammation in patients on peritoneal dialysis. Open-Label Trial: Effect of Weekly Risedronate Immediately After Transplantation in Kidney Recipients Effect of angiotensin receptor blockade on insulin sensitivity and endothelial function in abdominally obese hypertensive patients with impaired fasting glucose. Does calcium channel blocker improvement of perfusion impact the functioning of kidney graft in early period after transplantation? Effect of a single, oral, high-dose vitamin D supplementation on endothelial function in patients with peripheral arterial disease: a randomised controlled pilot study. Effect of short-term vitamin D supplementation on markers of vascular health in South Asian women living in the UK--a randomised controlled trial. Evaluation of endothelial function in women with polycystic ovary syndrome. The Effect of Calcium and Vitamin D3 Supplementation on the Healing of the Proximal Humerus Fracture: A Randomized Placebo-Controlled Study Effect of withdrawal of calcium and vitamin D supplements on bone mass in elderly men and women.
BACKGROUND Insulin therapy may influence cardiovascular disease ( CVD ) and lipid metabolism in type 2 diabetes ( T2D ) . Exaggerated postpr and ial lipaemia ( PPL ) is a feature of diabetic dyslipidaemia affecting CVD via enhanced oxidative stress ( OS ) and endothelial dysfunction . We assessed endothelial function and OS during PPL following insulin and vitamin C.  Twenty ( 17 M ) T2D patients were studied ( mean Hba1c 8.4 % ) at baseline , following 6 weeks of insulin lispro ( 0.2 Iu kg-1 ) and vitamin C 1-g  daily . Eight-h  lipid and glucose profiles were measured following a fatty meal .  Endothelial function ( flow-mediated vasodilatation : FMD ) and OS were measured at fasting , 4 h and 8 h. MATERIAL S AND METHODS Glucose , body mass index , and total and LDL cholesterol remained unchanged . FMD improved . Placebo group : fasting , 1.1 + /- 1.2 to 4.2 + /- 1.1 % ( P < 0.001 ) ; 4-h , 0.3 + /- 1.2 to 3.1 + /- 0.9 % ( P < 0.01 ) ; 8-h , 0.7 + /- 1.1 to 3.76 + /- 1.1 % ( P < 0.001 ) . Vitamin C group : fasting , 0.9 + /- 1.1 to 6.1 + /- 1.3 % ( P < 0.001 ) ; 4-h , 0.7 + /- 1.5 to 4.9 + /- 2.1 % ( P < 0.001 ) ; 8-h , 0.8 + /- 0.9 to 5.8 + /- 0.6 % ( P < 0.01 ) . Post-pr and ial lipaemia was attenuated : TG area-under-curve ( mmol L-1 8 h-1 ) , 52.6 + /- 11 to 39.1 + /- 12.5 ( placebo group ) , P < 0.02 ; and 56.9 + /- 8 to 40.1 + /- 10.3 ( vitamin C group ) , P < 0.02 . Oxidative stress was reduced , with greater changes in the vitamin C group . CONCLUSION Insulin may thus exert vascular benefits in T2D , by modifying fasting and postpr and ial lipid metabolism result ing in reduced OS and improved EF . Vitamin C therapy may augment the vascular benefits of insulin in T2D through additional effects on OS and EF BACKGROUND Vitamin D and calcium metabolism are involved in vascular smooth muscle cell proliferation , endothelial function and blood pressure ( BP ) regulation . Their physiopathology has been a matter of intensive clinical investigation with variable and sometimes contradictory results . Vitamin D insufficiency is highly prevalent in the general population , particularly among the elderly . We evaluated the association between serum 25(OH)-D levels and arterial BP in this population . METHODS An epidemiological cross-sectional study was design ed to analyse the prevalence of hypovitaminosis D ( ' D'AVIS ' study ) in our reference area . The study was performed on a representative r and om sample of the population over 64 years of age obtained from five primary health care areas . A medical record , arterial BP and biological analysis : serum 25(OH)-D , iPTH , creatinine , urea , calcium , albumin were obtained . RESULTS A total of 237 subjects ( 53 % women ) , aged between 64 and 93 ( mean 71.7 + /- 5.3 ) , were evaluated . The mean serum 25(OH)-D levels were 17.21 + /- 7.57 ng/ml ( interval 5 - 54 ; 86 % had < 25 ng/ml ) . The mean BP was 138.8 + /- 14/80 + /- 7.4 mmHg , and 46 % were on antihypertensive treatment . A significant negative association was observed between serum 25(OH)-D levels and systolic ( r = -0.153 , P = 0.018 ) and diastolic BP ( r = -0.152 , P = 0.019 ) . This association persisted after controlling for possible confounders in the multivariate analyses . CONCLUSIONS Low serum 25(OH)-D levels were inversely and independently associated with BP . Supplemental measures to prevent hypovitaminosis D in this population would be important , not only to protect the skeletal system but also for the possible beneficial effects on the cardiovascular system and the BP regulation Introduction Vitamin D has potential benefits for extraskeletal health . These could include an anti-inflammatory effect as well as a reduction in endothelial dysfunction . We aim to provide quality evidence for the hypothesis that supplementation with vitamin D will improve endothelial function ( EF ) , possibly through the abrogation of systemic inflammation . Methods and analysis We will conduct a systematic review of all r and omised controlled trials on  vitamin D supplementation and EF lasting 12 weeks or more . The search will cover the period 2000–2015 and include studies that describe direct measures of EF  , markers of endothelial cell ( EC ) activation  and if concurrently reported , indicators of systemic inflammation  . Study selection will follow the Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines and study quality will be assessed by the Jadad score in addition to an evaluation of allocation concealment and data analysis . If sufficient data are available , a meta- analysis will be conducted . The effect sizes will be generated using Hedges ’ g score , for both fixed and r and om effect models . I2 statistics and Galbraith plots will be used to assess heterogeneity and identify their potential sources . Potential publication and small sample size bias will be assessed by visual inspections of funnel plots and also Egger 's test . Meta-regression analysis ( if feasible ) will be conducted with restricted maximum likelihood ( REML ) estimation method , controlling for potential confounders ( demographics , study methods , location , etc ) . A backward elimination process will be applied in the regression modelling procedure . Subgroup analysis , conditional on number of studies retrieved and their sample size , will be stratified on participant disease category , total dose administered , degree of 25(OH)D change and type of supplement used . Ethics and dissemination Formal ethical approval is not required as primary data will not be collected . The results will be disseminated through a peer- review ed publication , conference presentation and the popular press . Trial registration number International Prospect i ve Register for Systematic Review s ( PROSPERO ) number CRD42014013523 Maternal obesity has a major impact on pregnancy outcomes . There is growing evidence that maternal obesity has a negative influence on placental development and function , thereby adversely influencing offspring programming and health outcomes . However , the molecular mechanisms underlying these processes are poorly understood . We analysed ten term placenta ’s whole transcriptomes in obese ( n = 5 ) and normal weight women ( n = 5 ) , using the Affymetrix microarray platform .  Analyses of expression data were carried out using non-parametric methods . Hierarchical clustering and principal component analysis showed a clear distinction in placental transcriptome between obese and normal weight women . We identified 72 differentially regulated genes , with most being down-regulated in obesity ( n = 61 ) . Functional analyses of the targets using DAVID and IPA confirm the dysregulation of previously identified processes and pathways in the placenta from obese women , including inflammation and immune responses , lipid metabolism , cancer pathways , and angiogenesis . In addition , we detected new molecular aspects of obesity-derived effects on the placenta , involving the glucocorticoid receptor signalling pathway and dysregulation of several genes including CCL2 , FSTL3 , IGFBP1 , MMP12 , PRG2 , PRL , QSOX1 , SERPINE2 and TAC3 . Our global gene expression profiling approach demonstrates that maternal obesity creates a unique in utero environment that impairs the placental transcriptome Angiogenesis is an important process in cell development , especially in cancer . Vascular endothelial growth factor ( VEGF ) signaling is an important regulator of angiogenesis . Several therapies that act against VEGF signal transduction have been developed , including YN968D1 , which is a potent inhibitor of the VEGF signaling pathway . This study investigated the antitumor activity of YN968D1 ( apatinib mesylate ) in vitro and in vivo . YN968D1 potently suppressed the kinase activities of VEGFR‐2 , c‐kit and c‐src , and inhibited cellular phosphorylation of VEGFR‐2 , c‐kit and PDGFRβ . YN968D1 effectively inhibited proliferation , migration and tube formation of human umbilical vein endothelial cells induced by FBS , and blocked the budding of rat aortic ring . In vivo , YN968D1 alone and in combination with chemotherapeutic agents effectively inhibited the growth of several established human tumor xenograft models with little toxicity . A phase I study of YN968D1 has shown encouraging antitumor activity and a manageable toxicity profile . These findings suggest that YN968D1 has promise as an antitumor drug and might have clinical benefits . ( Cancer Sci 2011 ; 102 : 1374–1380 Recent studies have shown that insulin has a direct vasodilator effect and that vascular sensitivity to insulin is impaired in hypertension . How the vasodilator effect of insulin is regulated physiologically is unknown . It has been appreciated that salt restriction may have adverse effects on glucose and lipid metabolism — processes regulated by insulin . To determine whether dietary salt restriction might affect vascular sensitivity to insulin , we studied 13 subjects ( including eight borderline hypertensive subjects and five normotensive subjects ) after 1 week of a normal sodium diet ( 240 mEq/day ) and after 1 week of a low‐sodium diet ( 20 mEq/day ) with a r and omized , double‐blind crossover design 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 Expression of bone proteins result ing from transdifferentiation of vascular smooth muscle cells into osteoblasts suggests that vascular calcifications are a bioactive process . Regulating molecules such as osteoprotegerin ( OPG ) and receptor activator of NF-kappaB lig and ( RANKL ) could play a key role in bone-vascular calcification imbalance . This study investigated the contribution of these proteins as well as mineral metabolism disorders in hemodialysis ( HD ) patient outcome . A total of 185 HD patients were followed up prospect ively for 2 yr . In addition to clinical characteristics , mineral metabolism markers as well as  OPG and soluble RANKL ( sRANKL )  were measured at baseline . After 2 yr , survival rates were described with Kaplan-Meier and compared with Cox regression analyses ; 50 patients died ( 27 from cardiovascular diseases ) . Calcium , phosphate , and calcium x phosphate product were not associated with mortality . Both hyperparathyroidism ( parathyroid hormone > or = 300 pg/ml ) and hypoparathyroidism ( parathyroid hormone < 150 pg/ml ) were poorly associated with all-cause and cardiovascular mortality . By contrast , elevated OPG levels predicted all-cause ( relative risk [ RR ] 2.67 ; 95 % confidence interval [ CI ] 1.32 to 5.41 ; P = 0.006 ) and cardiovascular mortality ( RR 3.15 ; 95 % CI 1.14 to 8.69 ; P = 0.03 ) . Low levels of sRANKL were associated with a protective effect for all-cause mortality ( RR 0.45 ; 95 % CI 0.21 to 0.94 ; P = 0.03 ) . The association of OPG with all-cause mortality was stronger in patients with C-reactive protein > or = 12.52 mg/L. In this condition , both highest ( RR 5.68 ; 95 % CI 1.48 to 22.73 ; P = 0.01 ) and lowest tertiles ( RR 5.37 ; 95 % CI 147 to 1968 ; P = 0.01 ) significantly predicted poor outcome . These results show that regulating-bone molecules , especially OPG , are strong predictors of mortality in HD patients , suggesting that OPG is a vascular risk factor , in particular in patients who have high C-reactive protein levels . OPG determination therefore should be added to the biologic follow-up of these patients Calcium and vitamin D are essential nutrients for bone health . Periods of activity with repetitive mechanical loading , such as military training , may result in increases in parathyroid hormone ( PTH ) , a key regulator of Ca metabolism , and may be linked to the development of stress fractures . Previous studies indicate that consumption of a Ca and vitamin D supplement may reduce stress fracture risk in female military personnel during initial military training , but circulating markers of Ca and bone metabolism and measures of bone density and strength have not been determined . This r and omized , double-blind , placebo-controlled trial sought to determine the effects of providing supplemental Ca and vitamin D ( Ca+Vit D , 2000 mg and 1000IU/d , respectively ) , delivered as 2 snack bars per day throughout 9weeks of Army initial military training ( or basic combat training , BCT ) on PTH , vitamin D status , and measures of bone density and strength in personnel undergoing BCT , as well as independent effects of BCT on bone parameters . A total of 156 men and 87 women enrolled in Army BCT ( Fort Sill , OK ; 34.7 ° N latitude ) volunteered for this study . Anthropometric , biochemical , and dietary intake data were collected pre- and post-BCT . In addition , peripheral quantitative computed tomography was utilized to assess tibia bone density and strength in a subset of volunteers ( n=46 ) . Consumption of supplemental Ca+Vit D  increased circulating ionized Ca ( group-by-time , P=0.022 ) , maintained PTH ( group-by-time , P=0.032 ) , and increased the osteoprotegerin : RANKL ratio ( group-by-time , P=0.006 ) . Consistent with the biochemical markers , Ca+Vit D  improved vBMD ( group-by-time , P=0.024 ) at the 4 % site and cortical BMC ( group-by-time , P=0.028 ) and thickness ( group-by-time , P=0.013 ) at the 14 % site compared to placebo . These data demonstrate the benefit of supplemental Ca and vitamin D for maintaining bone health during periods of elevated bone turnover , such as initial military training . This trial was registered with ClincialTrials.gov , NCT01617109 Background Wound healing is impaired in diabetes mellitus , but the mechanisms involved in this process are virtually unknown . Proteins belonging to the insulin signaling pathway respond to insulin in the skin of rats . Objective The purpose of this study was to investigate the regulation of the insulin signaling pathway in wound healing and skin repair of normal and diabetic rats , and , in parallel , the effect of a topical insulin cream on wound healing and on the activation of this pathway . Research Design and Methods We investigated insulin signaling by immunoblotting during wound healing of control and diabetic animals with or without topical insulin .  Diabetic patients with ulcers were r and omized to receive topical insulin or placebo in a prospect i ve , double-blind and placebo-controlled , r and omized clinical trial ( NCT 01295177 ) of wound healing . Results and Conclusions Expression of IR , IRS-1 , IRS-2 , SHC , ERK , and AKT are increased in the tissue of healing wounds compared to intact skin , suggesting that the insulin signaling pathway may have an important role in this process . These pathways were attenuated in the wounded skin of diabetic rats , in parallel with an increase in the time of complete wound healing . Upon topical application of insulin cream , the wound healing time of diabetic animals was normalized , followed by a reversal of defective insulin signal transduction . In addition , the treatment also increased expression of other proteins , such as eNOS ( also in bone marrow ) , VEGF , and SDF-1α in wounded skin . In diabetic patients , topical insulin cream markedly improved wound healing , representing an attractive and cost-free method for treating this devastating complication of diabetes . Trial Registration Clinical Trials.gov BACKGROUND Bone metabolism is a dynamic process that is influenced by food ingestion . Endogenous incretins have been shown to be important regulators of bone turnover . The aim of the present study was to assess whether a dipeptidylpeptidase (DPP)-4 inhibitor affects markers of bone resorption and calcium homeostasis . METHODS The present study was a single-center , double blind , r and omized clinical trail . Fifty-nine drug-naïve patients with type 2 diabetes ( T2D ) were r and omized to either 1 year treatment with the DPP-4 inhibitor vildagliptin ( 100 mg , once daily ; n = 29 ) or placebo ( n = 30 ) . Patients received a st and ardized breakfast after measurement of serum concentrations of cross-linked C-terminal telopeptide ( s-CTx ) , a bone resorption marker influenced by food intake , before and after 50 weeks treatment . RESULTS Vildagliptin did not change postpr and ial s-CTx concentrations compared with pretreatment levels ( between-group ratio 1.15 ± 0.17 ; P = 0.320 ) . Fasting serum alkaline phosphatase , calcium , and phosphate were also unaffected y 1 year treatment with vildagliptin . CONCLUSIONS Treatment with vildagliptin for 1 year was not associated with changes in markers of bone resorption and calcium homeostasis in drug-naïve patients with T2D and mild hyperglycemia Background Cardiovascular events are frequent and vascular endothelial function is abnormal in patients with chronic kidney disease ( CKD ) . We demonstrated endothelial dysfunction with vitamin D deficiency in CKD patients ; however the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function , endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [ 25(OH)D ] is unknown , which this study investigated . Methods We assessed non-diabetic patients with CKD stage 3/4 , age 17–80 years and serum 25(OH)D < 75 nmol/L.  Brachial artery Flow Mediated Dilation ( FMD ) , Pulse Wave Velocity ( PWV ) , Augmentation Index ( AI ) and circulating blood biomarkers were evaluated at baseline and at 16 weeks . Oral 300,000 units cholecalciferol was administered at baseline and 8-weeks . Results Clinical characteristics of 26 patients were : age 50±14 ( mean±1SD ) years , eGFR 41±11 ml/min/1.73 m2 , males 73 % , dyslipidaemia 36 % , smokers 23 % and hypertensives 87 % .  At 16-week serum 25(OH)D and calcium increased ( 43±16 to 84±29 nmol/L , p<0.001 and 2.37±0.09 to 2.42±0.09 mmol/L ; p = 0.004 , respectively ) and parathyroid hormone decreased ( 10.8±8.6 to 7.4±4.4 ; p = 0.001 ) . FMD improved from 3.1±3.3 % to 6.1±3.7 % , p = 0.001 . Endothelial biomarker concentrations decreased : E-Selectin from 5666±2123 to 5256±2058 pg/mL ; p = 0.032 , ICAM-1 , 3.45±0.01 to 3.10±1.04 ng/mL ; p = 0.038 and VCAM-1 , 54±33 to 42±33 ng/mL ; p = 0.006 . eGFR , BP , PWV , AI , hsCRP , von Willebr and factor and Fibroblast Growth Factor-23 , remained unchanged . Conclusion This study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness , serum calcium or FGF-23 . Trial Registration Clinical Trials.gov Objectives To examine whether combined vitamin D and calcium supplementation improves insulin sensitivity , insulin secretion , β-cell function , inflammation and metabolic markers . Design 6-month r and omized , placebo-controlled trial . Participants Ninety-five adults with serum 25-hydroxyvitamin D [ 25(OH)D ] ≤55 nmol/L at risk of type 2 diabetes ( with prediabetes or an AUSDRISK score ≥15 ) were r and omized . Analyses included participants who completed the baseline and final visits ( treatment n = 35 ; placebo n = 45 ) . Intervention Daily calcium carbonate ( 1,200 mg ) and cholecalciferol [ 2,000–6,000 IU to target 25(OH)D > 75 nmol/L ] or matching placebos for 6 months .  Measurements Insulin sensitivity ( HOMA2%S , Matsuda index ) , insulin secretion ( insulinogenic index , area under the curve ( AUC ) for C-peptide ) and β-cell function ( Matsuda index x AUC for C-peptide ) derived from a 75 g 2-h OGTT ; anthropometry ; blood pressure ; lipid profile ; hs-CRP ; TNF-α ; IL-6 ; adiponectin ; total and undercarboxylated osteocalcin . Results Participants were middle-aged adults ( mean age 54 years ; 69 % Europid ) at risk of type 2 diabetes ( 48 % with prediabetes ) . Compliance was > 80 % for calcium and vitamin D. Mean serum 25(OH)D concentration increased from 48 to 95 nmol/L in the treatment group ( 91 % achieved > 75 nmol/L ) , but remained unchanged in controls . There were no significant changes in insulin sensitivity , insulin secretion and β-cell function , or in inflammatory and metabolic markers between or within the groups , before or after adjustment for potential confounders including waist circumference and season of recruitment . In a post hoc analysis restricted to participants with prediabetes , a significant beneficial effect of vitamin D and calcium supplementation on insulin sensitivity ( HOMA%S and Matsuda ) was observed . Conclusions Daily vitamin D and calcium supplementation for 6 months may not change OGTT-derived measures of insulin sensitivity , insulin secretion and β-cell function in multi-ethnic adults with low vitamin D status at risk of type 2 diabetes . However , in participants with prediabetes , supplementation with vitamin D and calcium may improve insulin sensitivity . Trial Registration Australian New Zeal and Clinical Trials Registry 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 BACKGROUND Hyperphosphataemia is a known independent risk factor for cardiovascular mortality . The objective of the study was to compare the effects of two phosphate binders , sevelamer carbonate and calcium carbonate on endothelial function ( EF ) and inflammation in patients on peritoneal dialysis ( PD ) with Type 2 diabetes mellitus ( T2DM ) . METHODS Fifteen subjects with hyperphosphataemia discontinued all phosphate binders to undergo a two-week washout and were assigned to sevelamer carbonate or calcium carbonate treatments for eight weeks . After a second two-week washout period , subjects crossed over to either of the alternate treatments for another eight weeks . At the beginning and end of each treatment , biomarkers of EF , pro-inflammatory cytokines , serum albumin , calcium , phosphate and lipids were measured . RESULTS Sevelamer carbonate significantly improved lipid profile compared with calcium carbonate . Amongst the EF and pro-inflammatory biomarkers , sevelamer carbonate decreased serum endothelin-1 , plasminogen activator inhibitor-1 , C-reactive protein and interleukin-6 . Both phosphate binders were effective in decreasing serum phosphate but sevelamer had a positive effect on EF . CONCLUSIONS Treatment with sevelamer carbonate has beneficial effects compared with calcium carbonate in decreasing inflammation and improving EF in patients with T2DM on PD Background . Treatment with oral risedronate to prevent bone mineral density ( BMD ) loss in renal transplant recipients has been shown to be effective . There is no agreement on the optimum moment of introduction or how long it should be continued . The aim was to evaluate the effectiveness of risedronate at doses of 35 mg/week in renal transplant recipients who underwent treatment immediately after transplant . Methods . A r and omized clinical trial was performed on 101 renal transplant patients . The study group ( 52 patients ) received 35 mg risedronate weekly , vitamin D , and calcium , whereas the control group ( 49 patients ) received only vitamin D and calcium . At baseline , 3 , 6 , and 12 months , basic biochemistry and mineral bone metabolic parameters were determined . Vertebra and hip fracture assessment was performed by means of x-ray and DEXA ; an intention-to-treat analysis was performed . Results . Patients in control group showed a significant worsening of BMD ( P<0.05 ) 12 months into the study . At all follow-up points , lumbar BMD of the study group was significantly greater ( P<0.05 ) , whereas femoral BMD of those treated with risedronate was only significant at 6-month follow-up ( P<0.05 ) . There was a trend of more vascular calcifications and fractures in the control group , but this was not statistically significant . Conclusion . Weekly oral administration of risedronate immediately after renal transplantation contributes to an improved BMD , particularly in the femoral neck at 6-month follow-up , without major side effects . Long-term follow-up is needed to establish whether oral risedronate has an influence on vascular calcifications and bone fractures AngII ( angiotensin II ) may contribute to cardiovascular risk in obesity via adverse effects on insulin sensitivity and endothelial function . In the present study , we examined the effects of ARB ( angiotensin receptor blocker ) therapy ( losartan , 100 mg/day ) on insulin sensitivity and endothelial function in 53 subjects with stage I hypertension , abdominal obesity and impaired fasting glucose . The study design was a r and omized double-blinded parallel design placebo-controlled multi-centre trial of 8 weeks duration . We used the hyperinsulinaemic-euglycaemic clamp technique to measure insulin sensitivity ( expressed as the ' M/I ' value ) and RH-PAT ( reactive hyperaemia-peripheral arterial tonometry ) to measure endothelial function . Additional measures included HOMA ( homoeostasis model assessment ) -B , an index of pancreatic β-cell function , and markers of inflammation [ e.g. CRP ( C-reactive protein ) ] and oxidative stress ( e.g. F2-isoprostanes ) . ARB therapy did not alter insulin sensitivity [ 5.2 ( 2.7 ) pre-treatment and 4.6 ( 1.6 ) post-treatment ] compared with placebo therapy [ 6.1 ( 2.9 ) pre-treatment and 5.3 ( 2.7 ) post-treatment ; P value not significant ] , but did improve the HOMA-B compared with placebo therapy ( P=0.05 ) . ARB therapy also did not change endothelial function [ RH-PAT , 2.15 ( 0.7 ) pre-treatment and 2.11 ( 0.7 ) post-treatment ] compared with placebo therapy [ RH-PAT , 1.81 ( 0.5 ) pre-treatment and 1.76 ( 0.7 ) post-treatment ; P value not significant ] . Markers of inflammation and oxidative stress were not significantly changed by ARB therapy . In conclusion , ARB therapy did not alter peripheral insulin sensitivity or endothelial function in this cohort of patients with essential hypertension , abdominal obesity and impaired fasting glucose , but did improve pancreatic β-cell function The aim of the study was to evaluate the influence of reduced vascular resistance following calcium channel blocker verapamil administration on kidney function at 3 months after transplantation . A group of 48 kidneys received 100 microg verapamil by injection directly into renal artery before starting perfusion . The control group included 48 paired kidneys without verapamil addition . Calcium channel blocker therapy with verapamil greatly decreased renal vascular resistance but it did not affect graft function . Administration of calcium channel blockers improved kidney function in the early period after transplantation . A better-functioning graft seems to be based more on metabolic than hemodynamic effects OBJECTIVE Apart from its role in bone metabolism , vitamin D may also influence cardiovascular disease . The objective of this study was : ( 1 ) to determine the effect of a single , oral , high-dose vitamin D supplementation on endothelial function and arterial stiffness in patients with peripheral arterial disease ( PAD ) and ( 2 ) to investigate the impact of this supplementation on coagulation and inflammation parameters . METHODS In this double-blind , placebo-controlled , interventional pilot study , we screened 76 Caucasian patients with PAD for vitamin D deficiency . Sixty-two were r and omised to receive a single , oral supplementation of 100,000 IU vitamin D3 or placebo . At baseline and after 1 month , we measured serum vitamin D and parathormone levels , and surrogate parameters for cardiovascular disease . RESULTS Sixty-five of 76 patients ( 86 % ) had low 25-hydroxyvitamin D levels ( < 30 ng ml(-1 ) ) ; of those , 62 agreed to participate in the study . At baseline , only parathormone was related to vitamin D. In supplemented patients , vitamin D levels increased from 16.3 ± 6.7 to 24.3 ± 6.2 ng ml(-1 ) ( P < 0.001 ) , with wide variations between single patients ; in the placebo group vitamin levels did not change . Seasonal factors accounted for a decrease of vitamin D levels by 8 ng ml(-1 ) between summer and winter . After 1 month , none of the measured parameters was influenced by vitamin substitution . CONCLUSION In this pilot study , most patients with PAD were vitamin D deficient . Vitamin D supplementation  increased serum 25-hydroxyvitamin D without influencing endothelial function , arterial stiffness , coagulation and inflammation parameters , although the study was underpowered for definite conclusions OBJECTIVE Low vitamin D levels and risk factors for vascular disease are both common in South Asian women . This trial evaluated whether vitamin D supplementation could improve markers of vascular health in South Asian women with low 25-hydroxyvitamin D levels . METHODS Parallel-group , double-blind , r and omised placebo-controlled trial . Healthy South Asian women with baseline serum 25-hydroxyvitamin D levels of < 75 nmol/L were r and omised to receive a single dose of 100,000 units oral vitamin D3 or matching placebo . Outcomes were measured at baseline , 4 and 8 weeks . The primary outcome was change in endothelial function measured using brachial artery flow-mediated dilatation . Secondary outcomes included blood pressure , arterial stiffness , microvascular function measured using laser Doppler iontophoresis , insulin resistance , serum lipids , circulating markers of inflammation , thrombosis and adipokines . RESULTS 50 women were r and omised , 25 to each group . Mean age was 41 years ; mean baseline 25-hydroxyvitamin D level was 27 nmol/L.  25-Hydroxyvitamin D levels rose in the vitamin D group relative to the placebo group by 4 weeks ( 16 nmol/L , 95 % CI 11 to 21 , p < 0.001 ) . There was no improvement in flow-mediated dilatation in the vitamin D group relative to placebo at 4 weeks ( 0.1 % , 95 % CI -0.9 to 1.1 , p = 0.84 ) or 8 weeks ( 0.0 % , 95 % CI -1.4 to 1.4 , p = 0.98 ) . There was no improvement in cholesterol , insulin resistance or markers of inflammation . Both platelet activation inhibitor-1 and tissue plasminogen activator levels fell significantly in the vitamin D group relative to placebo at 8 weeks . CONCLUSION A single large dose of vitamin D3 did not improve blood pressure or endothelial function in South Asian women with low baseline 25-hydroxyvitamin D levels . TRIAL REGISTRATION IS RCT N75081811 OBJECTIVES Previous studies have suggested that vascular reactivity may be altered in women with polycystic ovary syndrome ( PCOS ) . We sought to evaluate the vascular reactivity specifically the endothelial function ( EF ) in women with PCOS and to study the effect of metformin on their EF . STUDY DESIGN Thirty-one women diagnosed with PCOS and 33 healthy controls underwent evaluation of EF using a post-ischemia reactive hyperemia technique ( Endo-PAT ) . EF was quantitatively determined as the ratio between the arterial pulse wave amplitude following a 5min arterial occlusion in the forearm to the pre-occlusion value . Oral metformin 850 mg bid was administered to PCOS patients . After 3 months of treatment EF was reassessed using the same technique . RESULTS The average endothelial function was 1.48+/-0.32 in the PCOS group versus 2.00+/-0.51 in the controls ( P<0.001 ) . There were no significant changes in the EF among the 18 patients who were treated with metformin  , EF index pre- and post-treatment was 1.42 versus 1.43 , respectively . CONCLUSIONS Endothelial dysfunction is more likely to occur among PCOS patients than in healthy controls . These preliminary results suggest that metformin treatment for 3 months in PCOS patients does not improve endothelial function The purpose of this study was to ( 1 ) quantify the healing process of the human osteoporotic proximal humerus fracture ( PHF ) expressed in terms of callus formation over the fracture region using BMD scanning , and ( 2 ) quantify the impact of medical intervention with vitamin D3 and calcium on the healing process of the human osteoporotic fracture . The conservatively treated PHF was chosen in order to follow the genuine fracture healing without influence of osteosynthetic material s or casts . Thirty women ( mean age = 78 years ; range = 58–88 ) with a PHF , osteoporosis or osteopenia ( based on a hip scan , WHO criteria ) , and not taking any drugs related to bone formation , including calcium or vitamin D supplementation  , were r and omly assigned to either oral 800 IU vitamin D3 plus 1 g calcium or placebo , in a double-blind prospect i ve study . We measured biochemical , radiographic , and bone mineral density effect parameters to evaluate the impact on the healing process . Scanning procedures of the fractured shoulder included use of a fixation device to obtain the highest possible precision . Double scans of the fractured shoulder revealed a coefficient of variation ( CV ) on BMD measurements that improved from 2.8 % immediately after fracture occurrence to 1.7 % at 12 weeks ( P = 0.003 ) approaching the 1.2 % levels observed over the healthy shoulder . BMD was similar in the two groups at baseline ( active 0.534 g/cm2 vs. placebo 0.518 g/cm2 ) , and both increased over the 12-week observation period , with peak levels in week 6 . By week 6 BMD levels were higher in the active group ( 0.623 g/cm2 ) compared with the placebo group ( 0.570 g/cm2 , P = 0.006 ) . Thirty seven percent of the patients presented with vitamin D levels below 30 nmol/l , indicative of mild vitamin D insufficiency . In conclusion , we have demonstrated that it is possible to quantify callus formation of the PHF with sufficiently high precision to demonstrate the positive influence of vitamin D3 and calcium over the first 6 weeks after fracture . Whether this results in more stable fractures , extends to other fracture types , or applies to other osteogenic bone agents such as bisphosphonates remains to be examined BACKGROUND Supplementation with calcium and vitamin D reduces bone loss and prevents fractures in elderly people , but it is not known whether any lasting benefit remains if the supplements are discontinued . OBJECTIVE The objective was to determine whether gains in bone mineral density ( BMD ) induced by calcium and vitamin D supplementation persist after supplement withdrawal . DESIGN Two-hundred ninety-five healthy , elderly men and women ( aged > /=68 y ) who had completed a 3-y r and omized , placebo-controlled trial of calcium and vitamin D supplementation were followed for an additional 2 y during which no study supplements were given .  BMD was measured by dual-energy X-ray absorptiometry , and biochemical variables related to calcium metabolism and bone turnover were measured . RESULTS In the 128 men , supplement-induced increases in spinal and femoral neck BMD were lost within 2 y of supplement discontinuation , but small benefits in total-body BMD remained . In the 167 women , there were no lasting benefits in total-body BMD or at any bone site . Consistent with the observations on BMD , the bone turnover rates in both men and women ( as measured by serum osteocalcin concentrations ) returned to their original higher concentrations within the same 2-y period . CONCLUSION Discontinued calcium and vitamin D supplementation has limited cumulative effect on bone mass in men and women aged > /=68
Conclusions Vitamin D supplementation did not improve EF .
The significant effect of vitamin D in diabetics and a tendency for an association with BMI may indicate a role of excess adiposity and insulin resistance in modulating the effects of vitamin D on vascular function .
Abstract Background In addition to regulating calcium homoeostasis and bone health , vitamin D influences vascular and metabolic processes including endothelial function ( EF ) and insulin signalling .