Impact of Vitamin D Replacement on Markers of Glucose Metabolism and Cardio-Metabolic Risk in Women with Former Gestational Diabetes--A Double-Blind, Randomized Controlled Trial.
ABSTRACT: Gestational Diabetes Mellitus (GDM) and vitamin D deficiency are related to insulin resistance and impaired beta cell function, with heightened risk for future development of diabetes. We evaluated the impact of vitamin D supplementation on markers of glucose metabolism and cardio metabolic risk in Asian women with former GDM and hypovitaminosis D. In this double blind, randomized controlled trial, 26 participants were randomized to receive either daily 4000 IU vitamin D3 or placebo capsules. 75 g Oral Glucose Tolerance Test (OGTT) and biochemistry profiles were performed at baseline and 6 month visits. Mathematical models, using serial glucose, insulin and C peptide measurements from OGTT, were employed to calculate insulin sensitivity and beta cell function. Thirty three (76%) women with former GDM screened had vitamin D level of <50 nmol/L at baseline. Supplementation, when compared with placebo, resulted in increased vitamin D level (+51.1 nmol/L vs 0.2 nmol/L, p<0.001) and increased fasting insulin (+20% vs 18%, p = 0.034). The vitamin D group also demonstrated a 30% improvement in disposition index and an absolute 0.2% (2 mmol/mol) reduction in HbA1c. There was no clear change in insulin sensitivity or markers of cardio metabolic risk. This study highlighted high prevalence of vitamin D deficiency among Asian women with former GDM. Six months supplementation with 4000 IU of vitamin D3 safely restored the vitamin D level, improved basal pancreatic beta-cell function and ameliorated the metabolic state. There was no effect on markers of cardio metabolic risk. Further mechanistic studies exploring the role of vitamin D supplementation on glucose homeostasis among different ethnicities may be needed to better inform future recommendations for these women with former GDM at high risk of both hypovitaminosis D and future diabetes.
Project description:Low vitamin D levels predict the development of diabetes. This double-blind, randomized, control study in subjects with prediabetes and hypovitaminosis D evaluated whether high doses of vitamin D for 1 year affected insulin secretion, insulin sensitivity, and the development of diabetes.A total of 1,551 subjects ≥40 years of age not known to have diabetes were screened with A1C levels. Subjects with A1C levels of 5.8-6.9% underwent an oral glucose tolerance test (OGTT). Subjects with prediabetes and 25-OH vitamin D (25-OHD) levels <30 ng/mL were randomized to receive weekly placebo (n = 53) or vitamin D (n = 56) with doses based on body weight and baseline 25-OHD levels. OGTTs were performed 3, 6, 9, and 12 months later. Insulin secretion and sensitivity were measured, and the proportion of subjects developing diabetes was assessed.25-OHD levels rapidly rose from 22 to nearly 70 ng/mL after vitamin D supplementation with a mean weekly dose of 88,865 IU. There were no differences between the placebo and vitamin D groups regarding fasting plasma glucose, 2-h glucose, or insulin secretion and sensitivity or in the percent developing diabetes or returning to normal glucose tolerance. No subjects experienced increased serum or urinary calcium levels. At 12 months, A1C levels were significantly slightly less (0.2%) in the vitamin D group.In individuals with prediabetes and hypovitaminosis D, doses of vitamin D supplementation designed to raise serum 25-OHD levels into the upper-normal range for 1 year had no effect on insulin secretion, insulin sensitivity, or the development of diabetes compared with placebo administration.
Project description:This double-blind, randomized, controlled trial evaluated whether 12 months of high-dose vitamin D2 supplementation improved insulin sensitivity and secretion and glycemic status.African-American males (AAM) with prediabetes (glycosylated hemoglobin [A1C] 5.7-6.4%), hypovitaminosis D (25-hydroxyvitamin D [25OHD] 5-29 ng/mL), and prevalent medical problems were supplemented with vitamin D3 (400 IU/day) and then randomized to weekly placebo or vitamin D2 (50,000 IU). The primary outcome was the change in oral glucose insulin sensitivity (OGIS, from an oral glucose tolerance test [OGTT]) after 12 months of treatment. Secondary outcomes included other glycemic indices, A1C, and incident diabetes.Baseline characteristics were similar in vitamin D-supplemented (n = 87) and placebo (n = 86) subjects completing the trial with average concentrations 14.4 ng/mL, 362 mL × min(-1) × m(-2), and 6.1% for 25OHD, OGIS and A1C, respectively. After 12 months, the vitamin D-supplemented group had a change in serum 25OHD +35 versus +6 ng/mL for placebo, P<.001; OGIS +7.8 versus -16.0 mL × min(-1) × m(-2) for placebo, P = .026; and A1C -0.01 versus +0.01% for placebo, P = .66. Ten percent of subjects in both groups progressed to diabetes. A posthoc analysis of participants with baseline impaired fasting glucose (IFG) showed that more subjects in the vitamin D subgroup (31.6%) than placebo (8.3%) returned to normal glucose tolerance, but the difference did not reach significance (P = .13).The trial does not provide evidence that 12 months of high-dose D2 repletion improves clinically relevant glycemic outcomes in subjects with prediabetes and hypovitaminosis D (NCT01375660).
Project description:OBJECTIVE:The aim was to investigate whether vitamin D supplementation, combined with a hypocaloric diet, could have an independent effect on insulin sensitivity in subjects with both overweight and hypovitaminosis D. Changes from baseline in anthropometric parameters, body composition, glucose tolerance, and insulin secretion were considered as secondary outcomes. METHODS:Eighteen volunteers who were nondiabetic and vitamin D deficient and had BMI?>?25 kg/m2 were randomized (1:1) in a double-blind manner to a hypocaloric diet?+?either oral cholecalciferol at 25,000 IU/wk or placebo for 3 months. Hyperinsulinemic-euglycemic clamp to measure insulin sensitivity was performed at baseline and after intervention. RESULTS:Body weight in both groups decreased significantly (-7.5% in the vitamin D group and -10% in the placebo group; P?<?0.05 for both), with no between-group differences. Serum 25-hydroxyvitamin D levels in the vitamin D group increased considerably (from 36.7?±?13.2 nmol/L to 74.8?±?18.7 nmol/L; P?<?0.001). Insulin sensitivity in the vitamin D group improved (from 4.6?±?2.0 to 6.9?±?3.3?mg·kg-1 ·min-1 ; P?<?0.001), whereas no changes were observed in the placebo group (from 4.9?±?1.1 to 5.1?±?0.3?mg·kg-1 ·min-1 ; P?=?0.84). CONCLUSIONS:Cholecalciferol supplementation, combined with a weight loss program, significantly improves insulin sensitivity in healthy subjects with obesity and might represent a personalized approach for insulin-resistant subjects with obesity.
Project description:BACKGROUND AND AIMS:Genetic variants involved in vitamin D metabolism have been associated with diabetes and related syndromes/diseases. We wanted to investigate possible associations of polymorphisms in genes involved in vitamin D metabolism with indices of insulin resistance and insulin secretion, and also with development of diabetes after gestational diabetes mellitus (GDM). MATERIALS AND METHODS:We have studied 376 women with previous GDM. Eight single nucleotide polymorphisms (SNPs) in the genes for vitamin D receptor (VDR) [rs731236, rs7975232, rs10735810, and rs1544410], vitamin D binding protein (DBP) [rs7041 and rs4588], and cytochrome P450 family 27 subfamily B member 1 (CYP27B1) [rs10877012 and rs4646536] were genotyped by TaqMan Allelic Discrimination Assay using the Quantstudio 7 Flex system. A 75-g oral glucose tolerance test (OGTT) was performed 1-2 years postpartum. The homeostasis model assessment of insulin resistance (HOMA-IR) and the disposition index [(insulinogenic index: I30/G30)/HOMA-IR] were used to calculate insulin resistance and insulin secretion, respectively. Serum samples for determination of 25(OH)D3 were collected at the time of the OGTT. Manifestation of diabetes was followed up to five years postpartum. RESULTS:After adjustment for BMI, age, and ethnicity, the A-allele of the VDR rs1544410 polymorphism was found to be associated with increased disposition index (difference per allele = 3.56, 95% CI: 0.4567-6.674; p = 0.03). The A-allele of the DBP rs7041 polymorphism was found to be associated with 25(OH)D3 levels (difference [in nmol/L] per allele = -5.478, 95% CI: -8.315 to -2.641; p = 0.0002), as was the T-allele of the DBP rs4588 polymorphism (OR = -6.319, 95% CI: -9.466 to -3.171; p = 0.0001). None of the SNPs were significantly associated with HOMA-IR or postpartum diabetes. CONCLUSIONS:This study provides evidence that the rs1544410 polymorphism of the VDR gene may be associated with increased insulin secretion in women after pregnancy complicated by GDM. Further studies in other populations are needed to confirm the results.
Project description:To examine whether combined vitamin D and calcium supplementation improves insulin sensitivity, insulin secretion, ?-cell function, inflammation and metabolic markers.6-month randomized, placebo-controlled trial.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 randomized. Analyses included participants who completed the baseline and final visits (treatment n?=?35; placebo n?=?45).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.Insulin sensitivity (HOMA2%S, Matsuda index), insulin secretion (insulinogenic index, area under the curve (AUC) for C-peptide) and ?-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-?; IL-6; adiponectin; total and undercarboxylated osteocalcin.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 ?-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.Daily vitamin D and calcium supplementation for 6 months may not change OGTT-derived measures of insulin sensitivity, insulin secretion and ?-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.Australian New Zealand Clinical Trials Registry ACTRN12609000043235.
Project description:PURPOSE:Vitamin D status may be associated with insulin resistance and other key features of polycystic ovary syndrome (PCOS), but data from preliminary randomized controlled trials (RCTs) are conflicting. Therefore, we aimed to investigate the effects of vitamin D supplementation on plasma glucose area under the curve (AUCgluc, primary outcome measure) and on other metabolic and endocrine parameters (secondary outcome measures). METHODS:This study was a single-center, double-blind, randomized placebo-controlled trial conducted between December 2011 and July 2017 at the Medical University of Graz, Austria. One-hundred and eighty women with PCOS and 25-hydroxyvitamin D [25(OH)D] concentrations <?75 nmol/L were randomized in a 2:1 ratio to either receive 20,000 IU of cholecalciferol weekly or placebo over 24 weeks. Primary outcome was the between-group difference in AUCgluc at study end while adjusting for baseline values. RESULTS:In total, 123 participants completed the study [age 25.9?±?4.7 years; BMI 27.5?±?7.3 kg/m2; baseline 25(OH)D 48.8?±?16.9 nmol/L, baseline fasting glucose 84?±?8 mg/dL]. Vitamin D supplementation lead to a significant increase in 25(OH)D [mean treatment effect 33.4 nmol/L; 95% confidence interval (CI) 24.5 to 42.2; p?<?0.001] but had no significant effect on AUCgluc (mean treatment effect -?9.19; 95% CI -?21.40 to 3.02; p?=?0.139). Regarding secondary outcome measures, we observed a significant decrease in plasma glucose at 60 min during oral glucose tolerance test (mean treatment effect -?10.2 mg/dL; 95% CI -?20.2 to -?0.3; p?=?0.045). CONCLUSIONS:Vitamin D supplementation had no significant effect on metabolic and endocrine parameters in PCOS with the exception of a reduced plasma glucose during OGTT.
Project description:Background:Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, and nutritional therapy is the basis of GDM treatment. However, the effects of different forms of nutritional supplementation on improving gestational diabetes are uncertain. Objective:We conducted a network meta-analysis to evaluate the effects of supplementation with different nutrients on glucose metabolism in women with GDM. Methods:We conducted a literature search using PubMed, EMBASE, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing the differences between different nutritional strategies in women with GDM. The Cochrane tool was used to assess the risk of bias. Pairwise meta-analysis and network meta-analysis were used to compare and rank the effects of nutritional strategies for the improvement of fasting plasma glucose (FPG), serum insulin, and homeostasis model assessment-insulin resistance (HOMA-IR). Results:We included thirteen RCTs with a total of 754 participants. Compared with placebo, omega-3, magnesium, vitamin D, zinc, and probiotics were more beneficial for improving FPG, serum insulin, and HOMA-IR. Network analysis showed that vitamin D supplementation was superior to omega-3 (-3.64?mg/dL, 95% CI: -5.77 to -1.51), zinc (-5.71?mg/dL, 95% CI: -10.19 to -1.23), probiotics (-6.76?mg/dL, 95% CI: -10.02 to -3.50), and placebo (-12.13?mg/dL, 95% CI: -14.55 to -9.70) for improving FPG. Magnesium supplementation was more beneficial for decreasing serum insulin compared with probiotics (-5.10??IU/mL, 95% CI: -9.32 to -0.88) and placebo (-7.80??IU/mL, 95% CI: -9.32 to -0.88) and placebo (-7.80?. Conclusion:Vitamin D supplementation significantly reduced FPG and regulated HOMA-IR. Magnesium supplementation was superior in decreasing serum insulin than supplementation with other nutrients. Nutrient supplementation seemed to have an effect on glucose homeostasis maintenance in patients with GDM and may be considered an adjunctive therapy.
Project description:Background:Vitamin D deficiency is associated with indicators of pre-diabetes including, insulin resistance, ?-cell dysfunction and elevated plasma glucose with controversial findings from current trials. This study aims to investigate the long-term effect of vitamin D on glucose metabolism and insulin sensitivity in pre-diabetic and highly vitamin-deficient subjects. Methods:One hundred thirty-two participants were randomized to 30,000?IU vitamin D weekly for 6?months. Participants underwent oral glucose tolerance test (OGTT) at 3-month intervals to determine the change in plasma glucose concentration at 2?h after 75?g OGTT (2hPCG). Secondary measurements included glycated hemoglobin, fasting plasma glucose and insulin, post-prandial insulin, indices of insulin sensitivity (HOMA-IR, Matsuda Index), ?-cell function (HOMA-?, glucose and insulin area under the curve (AUC), disposition and insulinogenic indices), and lipid profile. Results:A total of 57 (vitamin D) and 75 (placebo) subjects completed the study. Mean baseline serum 25(OH) D levels were 17.0?ng/ml and 14.9?ng/ml for placebo and vitamin D group, respectively. No significant differences were observed for 2hPC glucose or insulin sensitivity indices between groups. HOMA-? significantly decreased in the vitamin D group, while area under curve for glucose and insulin showed a significant reduction in ?-cell function in both groups. Additionally, HOMA-? was found to be significantly different between control and treatment group and significance persisted after adjusting for confounding factors. Conclusion:Vitamin D supplementation in a pre-diabetic and severely vitamin-deficient population had no effect on glucose tolerance or insulin sensitivity. The observed reduction in ?-cell function in both placebo and vitamin D groups could be attributed to factors other than supplementation. Trial registration:NCT02098980, 28/03/2014 (www.clinicaltrials.gov).
Project description:Vitamin D insufficiency may increase the risk for cardio metabolic disturbances in patients with primary hyperparathyroidism (PHPT).To analyze the vitamin D status and indices of the metabolic syndrome in PHPT patients and the effect of vitamin D supplementation after parathyroid adenomectomy (PTX).Double-blinded, randomized clinical trial (ClinicalTrials.gov identifier: NCT00982722) performed at Karolinska University Hospital, Sweden, April 2008 to November 2011. One hundred and fifty consecutive patients with PHPT (119 women) were randomized after PTX, 75 to oral treatment with calcium carbonate 1000?mg daily and 75 to calcium carbonate 1000?mg and cholecalciferol 1600?IU daily over 12 months. Changes in metabolic profile and ambulatory blood pressure (BP) were analyzed. Main outcome measures were changes in metabolic factors, BP, and body composition.The 25-hydroxyvitamin D (25-OH-D)-level was <50?nmol/l in 76% of the patients before PTX. After PTX, glucose, insulin, and IGF1 decreased, while the 25-OH-D and the IGF-binding protein 1 increased and remained unchanged at follow-up after study medication. One year of vitamin D supplementation resulted in lower parathyroid hormone (PTH) (40 (34-52) vs 49 (38-66) ng/l) and higher 25-OH-D (76 (65-93) vs 49 (40-62) nmol/l; P<0.05). Other laboratory parameters were stable compared with after PTX. Systolic BP decreased and total bone mineral content increased in both groups.Except for the lowering of the PTH level, no additive effect of vitamin D supplementation was seen. However, PTX proved effective in reducing insulin resistance.
Project description:The aim of this study was survey of the effect of Vitamin D supplementation on the incidence of gestational diabetes (GDM) in pregnant women.This randomized clinical trial was conducted at Alzahra and Shahid Beheshti Hospital in Isfahan, Iran, from January, 2013 to January, 2014 on 210 pregnant women referred to gynecology clinics. Serum levels of Vitamin D were measured, and those with lower serum levels of 10 nmol/L randomly divided into two groups of A and B. Pregnant women with normal Vitamin D level assigned as Group C. Group A was given 50,000 IU Vitamin D supplement every 2 weeks for 10 weeks, and Group B were given the omega-3 pearl as placebo. Then, the incidence of GDM was measured in 24-26 weeks of pregnancy with glucose tolerance test and compared in three groups. Data were analyzed using SPSS version 20 by descriptive statistics, Chi-square and Logistic regression.The mean age of participants was 24.76 years (8.02 standard deviation, range 16-36 years). The incidence of GDM at 24-26 weeks gestational age were 8.57% in normal Vitamin D group, 10.00% in Vitamin D deficiency with treatment group, and 11.43% in Vitamin D deficiency without treatment group. The difference between groups in terms of incidence of GDM was not statistically significant (P = 0.112).Vitamin D supplementation had not effect on incidence of GDM during pregnancy.