title: Intravenous 1,25 dihydroxycholecalciferol corrects glucose intolerance in hemodialysis patients. Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial. Effect of 1,25 (OH)2D3 treatment on glucose intolerance in uraemia. Effect of oral calcitriol pulse therapy on the lipid, calcium, and glucose homeostasis of hemodialysis-patients: its safety in a combination with oral calcium carbonate. Effects of intravenous calcitriol on lipid profiles and glucose tolerance in uraemic patients with secondary hyperparathyroidism. Effect of Activated Vitamin D on Glucoparameters in HCV Seropositive and Seronegative Patients on Chronic Hemodialysis A pilot study of active vitamin D administration and insulin resistance in African American patients undergoing chronic hemodialysis. Impact of treatment with oral calcitriol on glucose intolerance and dyslipidemia(s) in hemodialysis patients.
abstract: The effects of intravenous 1,25 dihydroxycholecalciferol [ (OH)2D3 ] on glucose tolerance and insulin secretion were studied in eleven uremic patients on regular hemodialysis and compared with eleven healthy controls . Intravenous glucose tolerance tests ( IVGTT ) were used to assess glucose tolerance , and the hyperglycemic clamp technique was used to quantitate endogenous insulin secretion . Three days after they had discontinued oral 1,25(OH)2D3 , the dialysis patients were then studied with ( + D ) and without ( -D ) a single intravenous dose of 1,25(OH)2D3 at 2 micrograms/m2 , given two hours before the IVGTT or clamp studies . During the -D studies , the uremic patients were glucose intolerant but not hyperinsulinemic . Intravenous 1,25(OH)2D3 in dialysis patients increased glucose uptake ( K values ) during IVGTT by 38 % ( P less than 0.02 ) and increased early component of insulin secretion during hyperglycemic clamps by 48 % ( P less than 0.01 ) and the late component by 32 % ( P less than 0.01 ) . After intravenous 1,25(OH)2D3 , the dialysis patients became hyperinsulinemic and regained glucose tolerance . Intravenous 1,25(OH)2D3 did not change the K values during IVGTT nor the insulin secretion during hyperglycemic clamps in the control subjects . During the -D studies , serum concentrations of 1,25(OH)2D3 were significantly lower in uremic patients compared with controls . Serum 1,25(OH)2D3 during the + D studies increased to supraphysiological levels in both uremic patients and controls . Serum concentrations of intact parathyroid hormone , total and ionized calcium , magnesium , potassium , urea nitrogen and creatinine were not different between the + D and -D studies in neither the uremic patients nor the controls . These results suggest that 1,25(OH)2D3 deficiency , independent of parathyroid hormone and calcium , may contribute to the abnormalities in glucose tolerance and insulin secretion in dialysis patients CONTEXT Vitamin D is associated with decreased cardiovascular-related morbidity and mortality , possibly by modifying cardiac structure and function , yet firm evidence for either remains lacking . OBJECTIVE To determine the effects of an active vitamin D compound , paricalcitol , on left ventricular mass over 48 weeks in patients with an estimated glomerular filtration rate of 15 to 60 mL/min/1.73 m(2 ) . DESIGN , SETTING , AND PARTICIPANTS Multinational , double-blind , r and omized placebo-controlled trial among 227 patients with chronic kidney disease , mild to moderate left ventricular hypertrophy , and preserved left ventricular ejection fraction , conducted in 11 countries from July 2008 through September 2010 . INTERVENTION Participants were r and omly assigned to receive oral paricalcitol , 2 μg/d ( n = 115 ) , or matching placebo ( n = 112 ) . MAIN OUTCOME MEASURES Change in left ventricular mass index over 48 weeks by cardiovascular magnetic resonance imaging . Secondary end points included echocardiographic changes in left ventricular diastolic function . RESULTS Treatment with paricalcitol  reduced parathyroid hormone levels within 4 weeks and maintained levels within the normal range throughout the study duration . At 48 weeks , the change in left ventricular mass index did not differ between treatment groups ( paricalcitol group , 0.34 g/m(2.7 ) [ 95 % CI , -0.14 to 0.83 g/m(2.7 ) ] vs placebo group , -0.07 g/m(2.7 ) [ 95 % CI , -0.55 to 0.42 g/m(2.7 ) ] ) . Doppler measures of diastolic function including peak early diastolic lateral mitral annular tissue velocity  ( paricalcitol group , -0.01 cm/s [ 95 % CI , -0.63 to 0.60 cm/s ] vs placebo group , -0.30 cm/s [ 95 % CI , -0.93 to 0.34 cm/s ] ) also did not differ . Episodes of hypercalcemia were more frequent in the paricalcitol group compared with the placebo group . CONCLUSION Forty-eight week therapy with paricalcitol did not alter left ventricular mass index or improve certain measures of diastolic dysfunction in patients with chronic kidney disease . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00497146 The aim of this study was to evaluate the effect of calcitriol treatment on glucose intolerance in uraemia . Thirty one patients on haemodialysis who had never been treated with vitamin D or related drugs , and 12 healthy control subjects with normal renal functions were studied . Uraemic patients were r and omly divided into two groups ; 16 patients were treated with oral calcitriol ( 0.5 micrograms/day ) for 8 weeks , and 15 uraemic patients and 12 healthy subjects were given a placebo . In all these cases , before and 8 weeks after treatment , baseline serum glucose , insulin , calcium , parathormone ( PTH ) , and 1,25 (OH)2D3 were measured . After an oral load of 75 g glucose , blood glucose and insulin  were determined at 30 , 60 , 90 , and 120 min . The same measurements were repeated after 8 weeks . HbA1c and fructosamine were also measured at 0 and 8 weeks . Baseline serum insulin was significantly elevated after calcitriol treatment ( 7.81 versus 11.63 microIU/ml ) there was also a significant increase in insulin following calcitriol treatment at 30 , 60 , 90 , and 120 min . On the other h and , glycosylated haemoglobin ( HbA1c ) and fructosamine decreased after calcitriol treatment ( HbA1c 7.09 % versus 5.22 % P < 0.01 and fructosamine 2.92 versus 2.50 mmol/l P < 0.01 ) . Blood glucose significantly decreased after calcitriol treatment at 0 , 30 , 60 , 90 , and 120 min . In the other two groups there were no significant changes in any parameters . These results seem to confirm that vitamin D influences pancreatic beta ( beta ) cell secretion and suggest that calcitriol may improve glucose intolerance in uraemic haemodialysis patients . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To more clearly eluci date the conflicting results that have been obtained after oral calcitriol pulse therapy on lipid , glucose , and calcium levels in hemodialysis ( HD ) patients , and to determine safety of oral calcitriol pulse therapy in a combination with calcium carbonate . DESIGN A r and omized , crossover , placebo-controlled study . SETTING HD centers in 3 teaching university hospitals . PATIENTS Forty-eight chronic HD patients . METHODS HD patients were r and omized into 2 groups . Each group ( n = 24 ) , in addition to 4.5 g calcium carbonate daily , received either oral calcitriol pulse therapy or placebo twice weekly at the end of HD , sessions for 3 months , after which the 2 therapeutic groups were crossed-over , and for an additional 3 months , the calcitriol group received placebo , and the placebo group was put on calcitriol .  Serum triglyceride , total cholesterol , low-density lipoprotein cholesterol ( LDL-c ) , high-density lipoprotein cholesterol ( HDL-c ) , total calcium , alkaline phosphatase , proteins , phosphorus , parathyroid hormone ( PTH ) , blood pH , and glucose were measured at r and om and at the end of 3 and 6 months of the trial . RESULTS After calcitriol therapy , triglyceride , serum PTH , total alkaline phosphatase , and fasting blood sugar significantly decreased , but total serum calcium significantly increased , whereas other examined parameters remained unchanged compared with the other groups . Calcium , phosphorus , calcium x phosphorus product , PTH levels , and all of these parameters were optimized in 18 ( 37.5 % ) , 22 ( 45.8 % ) , 34 ( 70.8 % ) , 30 ( 62.5 % ) , and 12 ( % 25 ) cases , respectively , in the calcitriol groups . No significant side effect was seen during the trial . CONCLUSION Our findings indicate that short-term oral calcitriol pulse therapy in combination with calcium carbonate is safe and beneficial for metabolic abnormalities of HD patients ; however , its safety for prolonged therapy is yet to be proved 1 . Secondary hyperparathyroidism in chronic renal failure may contribute to abnormalities of lipid metabolism and glucose tolerance . Amelioration of secondary hyperparathyroidism has been reported to mitigate the hyperlipidaemia and improve glucose tolerance experimentally . 2 . The effect of the partial suppression of hyperparathyroidism by intravenous calcitriol on lipid levels and glucose tolerance was studied in 15 haemodialysis patients with secondary hyperparathyroidism . All received intravenous calcitriol 1 microgram at the end of haemodialysis thrice weekly for eight weeks . Oral glucose tolerance test and plasma lipid profiles including triglyceride , total cholesterol , high density lipoprotein cholesterol ( HDL-C ) , low density lipoprotein cholesterol ( LDL-C ) , apoprotein A-I and apoprotein B were determined simultaneously before and after eight weeks of therapy . 3 . Before calcitriol treatment , uraemic patients with secondary hyperparathyroidism displayed a significant higher triglyceride and a significant lower HDL-C and apoprotein A-I as well as marked glucose intolerance with an increment of the area below the glucose curve when compared with healthy control subjects . 4 . After eight weeks of calcitriol treatment , there was a significant decrement in serum intact parathyroid hormone ( 476.45 + /- 48.33 versus 191.37 + /- 30.17 ng/l , P < 0.001 ) and plasma triglyceride ( 2.24 + /- 0.34 versus 1.80 + /- 0.29 mmol/l , P < 0.05 ) as well as a significant increment of plasma apoprotein A-I ( 38.13 + /- 2.14 versus 44.19 + /- 2.18 mumol/l , P < 0.05 ) , whereas there was no significant change in serum total cholesterol , LDL-C , HDL-C , and apoprotein B. ( ABSTRACT TRUNCATED AT 250 WORDS Introduction : Many studies support the role of vitamin D in the pathogenesis of both types of diabetes . Pancreatic tissues express the vitamin D receptor ( VDR ) and vitamin D-binding protein ; some allelic variations in genes involved in vitamin D metabolism and VDR are associated with glucose intolerance , defective insulin secretion , and sensitivity . Epidemiological links have been established between type 2 diabetes mellitus ( DM ) and hepatitis C virus ( HCV ) infection . Aim : To explore the possible therapeutic potential of pharmacologic doses of 1-α-hydroxy vitamin D therapy in improving pancreatic β-cell function in HCV seropositive hemodialysis ( HD ) patients . Patients and methods : Twenty HCV seropositive HD patients and 20 HCV seronegative patients as control group were r and omly selected from HD units .  1-α-Hydroxy vitamin D therapy was administrated in the dose ranged from 0.25 to 0.5 μg/day for 3 months  . Corrected total serum calcium , phosphorus , intact parathyroid hormone ( iPTH ) , 25-hydroxy vitamin D [ 25(OH ) vitamin D ] , 1,25-dihydroxy vitamin D , and glucoparameters [ fasting blood glucose , glycohemoglobin test ( HbA1c% ) , homeostatic model assessment (HOMA)-insulin resistance , and HOMA-β-cell function% ( B% ) ] were measured under basal conditions and after 3 months of therapy . Results : There was highly significant improvement in the concentrations of fetal bovine serum ( FBS ) , serum insulin , HbA1c% , 25(OH ) vitamin D , and HOMA-β-cell function in HCV seropositive and HCV seronegative groups after oral 1-alphacalcidiol therapy ( p < 0.001 ) . Positive correlation exists between the percentage increase in serum insulin and that in HOMA-β-cell function versus 25(OH ) vitamin D ( p < 0.021 and p < 0.027 , respectively ) in HCV negative group . Conclusion : 1-α-Hydroxy vitamin D oral therapy may improve glycemic control in HCV seropositive and HCV seronegative HD patients OBJECTIVE Insulin resistance ( IR ) is associated with increased cardiovascular risk in multiple patient population s , including those undergoing chronic hemodialysis ( CHD ) . Active vitamin D deficiency has been proposed to play a role in the extent of IR observed in patients with CHD . We postulated that administration of paracalcitol , an active vitamin D medication , influences IR in patients with CHD . DESIGN AND METHODS This was a pilot r and omized controlled trial . Ten prevalent CHD patients receiving a stable dose of paracalcitol were recruited .  Paracalcitol was withheld for 8 weeks in all patients ( phase I ) . Parathyroid hormone levels were managed with the calcium-sensing receptor agonist cinacalcet . At week 8 , patients were r and omized to continue cinacalcet or to restart paracalcitol for 8 weeks ( phase II ) . The primary outcome was the change in IR measured by the glucose disposal rate ( GDR ) using hyperinsulinemic euglycemic clamp ( HEGC ) method . Secondary outcomes included changes in IR between groups in indirect indices of IR , biomarkers of inflammation , and adipokine levels . RESULTS The mean age was 49 years ( range , 46 - 57 years ) and 40 % of patients were women . There was no detectable change in the GDR at the end of phase I ( P = .7 ) when compared with baseline values . There was also no statistically significant difference in GDR between groups at the end of phase II ( P = .9 ) . No changes were observed in indirect indices of IR , adipokine levels , or biomarkers of inflammation in either phase . CONCLUSION The results of this pilot study suggest that withdrawal of paracalcitol over 8 to 16 weeks and replacement for 8 weeks after withdrawal does not influence IR measured by HEGC in patients receiving CHD This study was conducted to assess the effect of oral calcitriol on glucose metabolism in patients on hemodialysis ( HD ) . A total of 27 patients on HD at the Mashhad University of Medical Sciences , Iran , none of whom had received calcitriol or had history of diabetes , were selected . The patients were r and omly divided into two groups ; Group I : patients who received oral calcitriol for eight weeks and , Group II : patients who received placebo . In all cases , levels of fasting glucose , insulin , lipid profile , calcium , phosphorous , parathormone ( PTH ) , HbA1C and blood sugar after administration of 75 grams of glucose , insulin resistance and beta cell function were measured , before and after the treatment period . The two sets of results were then compared with one another . In Group l patients , the levels of the parameters studied before and after the study period were as follows : blood sugar after 75 grams of glucose ( 88.67 + /- 8.68 versus 99.83 + /- 34.42 mg/dL , p = 0.045 ) , HOMA-IR ( 2.05 + /- 1.42 versus 2.42 + /- 1.33 , p = 0.035 ) , HbA1C ( 5.99 + /- 1.00 versus 6.14 + /- 1.19 , p= < 0.001 ) , total cholesterol ( 153.3 + / 43.80 mg/dl versus 157.0 + /52.62 , p = 0.037 ) and triglycerides ( 175.30 + /- 99.65 versus 214.9 + /- 117.7 mg/dL , p = 0.036 ) . Thus , there was a significant decrease after the study period . In Group II , fasting blood sugar ( 110.7 + /- 26.12 versus 81.14 + /- 13.31 mg/dL , p = 0.002 ) , HbA1C ( 6.99 + /- 1.44 versus 6.17 + /- 1.66 , p = 0.004 ) and HOMA-IR ( 5.85 + /- 5.11 versus 3.20 + /- 2.39 , p = 0.036 ) significantly increased and beta cell function significantly decreased ( 149.5 + /- 90.57 versus 355.7 + /- 299.3 , p = 0.032 ) after the study period . In conclusion , our results show that vitamin D has a significant influence on glucose metabolism . Similar studies on larger sample size are required to confirm this observation
target: Conclusions Short-term ( 4–12 weeks ) supplementation with vitamin D is associated with lower fasting glucose levels in ESRD with no change in fasting insulin levels .
background: Abstract Purpose We tested whether short-term vitamin D supplementation improves insulin resistance in patients with kidney disease , a condition with little intrinsic vitamin D activity .