cholecalciferol and Insulin-Resistance

In the last decade, an increasing awareness was directed to the role of Vitamin D in non-skeletal and preventive roles for chronic diseases. Vitamin D is an essential hormone in regulating calcium/phosphorous balance and in the pathogenesis of inflammation, insulin resistance, and obesity. The main forms of vitamin D, Cholecalciferol (Vitamin D3) and Ergocalciferol (Vitamin D2) are converted into the active form (1,25-dihydroxyvitamin D) thanks to two hydroxylations in the liver, kidney, pancreas, and immune cells. Some anti-inflammatory cytokines are produced at higher levels by vitamin D, while some pro-inflammatory cytokines are released at lower levels. Toll-Like Receptor (TLR) expression is increased, and a pro-inflammatory state is also linked to low levels of vitamin D. Regardless of how it affects inflammation, various pathways suggest that vitamin D directly improves insulin sensitivity and secretion. The level of vitamin D in the body may change the ratio of pro- to anti-inflammatory cytokines, which would impact insulin action, lipid metabolism, and the development and function of adipose tissue. Many studies have demonstrated an inverse relationship between vitamin D concentrations and pro-inflammatory markers, insulin resistance, glucose intolerance, metabolic syndrome, obesity, and cardiovascular disease. It is interesting to note that several long-term studies also revealed an inverse correlation between vitamin D levels and the occurrence of diabetes mellitus. Vitamin D supplementation in people has controversial effects. While some studies demonstrated improvements in insulin sensitivity, glucose, and lipid metabolism, others revealed no significant effect on glycemic homeostasis and inflammation. This review aims to provide insight into the molecular basis of the relationship between vitamin D, insulin resistance, metabolic syndrome, type 1 and 2 diabetes, gestational diabetes, and cardiovascular diseases.

Topics: Anti-Inflammatory Agents; Cardiovascular Diseases; Cholecalciferol; Cytokines; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Inflammation; Insulin; Insulin Resistance; Metabolic Syndrome; Obesity; Pregnancy; Vitamin D; Vitamin D Deficiency; Vitamins

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. It is characterized by hormonal, reproductive and metabolic disturbances, including hyperandrogenism, altered gonadotropin level, ovarian cysts and ovulatory dysfunction as well as insulin resistance, hyperinsulinemia and dyslipidemia. It was shown that increased insulin concentration is a plausible factor in the pathogenesis of PCOS. Insulin leads to overstimulation of ovarian theca cells to androgen biosynthesis and contributes to insulin resistance in tissues such as muscle, liver, adipose tissue and ovary of PCOS patients. Noteworthy, recent studies suggested that supplementation with vitamin D

Topics: Animals; Cholecalciferol; Female; Humans; Insulin; Insulin Resistance; Polycystic Ovary Syndrome

Evidence of synergic health effects of co-supplementation with vitamin D and probiotics is emerging. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA statement, scientific databases and the grey literature were searched, and a narrative review and risk of bias assessment were conducted. Seven randomized controlled trials were included, which had low risk of bias. Six studies were double-blind, and once single-blind, extended over 6-12 weeks, and included 50-105 participants. Conditions explored included schizophrenia, gestational diabetes, type 2 diabetes and coronary heart disease, polycystic ovarian syndrome, osteopenia, irritable bowel syndrome (IBS), and infantile colic. Supplementation frequency was daily or bi-monthly, with mainly vitamin D3, and

Topics: Bifidobacterium; Cholecalciferol; Dietary Supplements; Dyslipidemias; Female; Humans; Inflammation; Insulin Resistance; Lactobacillus; Male; Mental Health; Probiotics; Randomized Controlled Trials as Topic; Streptococcus

Nonalcoholic fatty liver disease (NAFLD) and vitamin D3 deficiency are two highly prevalent pathologic conditions worldwide that share several cardiometabolic risk factors. In addition to its traditional calcium-related effects on the skeleton, vitamin D3 deficiency has now been recognized to exert nonskeletal adverse effects on several other organ systems. Accumulating epidemiological evidence suggests that low levels of serum 25-hydroxyvitamin D3 are associated with the presence and severity of NAFLD, independently of several potential confounders, including features of the metabolic syndrome. The molecular mechanisms of this association remain incompletely understood. A variety of biologically plausible mechanisms may mediate a hepato-protective role for the active metabolite of vitamin D3. 1α,25-dihydroxyvitamin D3 modulates the insulin signaling pathway/insulin resistance, suppresses fibroblast proliferation and collagen production, exerts anticoagulant and profibrinolytic effects, and modulates macrophage activity and inflammatory cytokine generation. Overall, the high prevalence of vitamin D3 deficiency and the plausible biological mechanisms linking this to NAFLD suggest that treatment of vitamin D3 deficiency to prevent and/or treat NAFLD is a promising field to explore. Large placebo-controlled randomized clinical trials are urgently needed to determine whether vitamin D3 supplementation could have any potential benefit in reducing the development and progression of NAFLD.

Topics: Adipose Tissue; Bile; Bile Acids and Salts; Cholecalciferol; Fatty Liver; Humans; Immunologic Factors; Insulin Resistance; Intestinal Mucosa; Models, Biological; Non-alcoholic Fatty Liver Disease; Risk Factors; Signal Transduction; Vitamin D Deficiency

Topics: Absorptiometry, Photon; Animals; Biomarkers; Bone and Bones; Bone Density; Bone Density Conservation Agents; Cholecalciferol; Collagen; Diabetes Complications; Diphosphonates; Fractures, Bone; Glycation End Products, Advanced; Humans; Insulin Resistance; Insulin-Like Growth Factor I; Osteoporosis

Topics: Calcium; Calcium, Dietary; Cholecalciferol; Dietary Supplements; Double-Blind Method; Humans; Insulin Resistance; Insulin-Secreting Cells; Prediabetic State; Vitamin D; Vitamins

High-dose vitamin D supplementation can increase total osteocalcin concentrations that may reduce insulin resistance in individuals at risk for prediabetes or diabetes mellitus. Magnesium is a cofactor in vitamin D metabolism and activation. The purpose of this study was to determine the combined effect of vitamin D and magnesium supplementation on total osteocalcin concentrations, glycemic indices, and other bone turnover markers after a 12-week intervention in individuals who were overweight and obese, but otherwise healthy. We hypothesized that combined supplementation would improve serum total osteocalcin concentrations and glycemic indices more than vitamin D supplementation alone or a placebo. A total of 78 women and men completed this intervention in 3 groups: a vitamin D and magnesium group (1000 IU vitamin D

Topics: Bone Remodeling; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin Resistance; Magnesium; Male; Obesity; Osteocalcin; Overweight; Vitamin D; Vitamin D Deficiency; Vitamins

Vitamin D regulates glucose homeostasis pathways, but effects of vitamin D supplementation on β-cell function remain unclear.. To investigate the effects of vitamin D3 supplementation on insulin sensitivity and β-cell function.. This is a prespecified secondary analysis of the Vitamin D and Type 2 Diabetes study. Overweight/obese adults at high risk for type 2 diabetes (prediabetes) were randomly treated with vitamin D3 4000 IU or matching placebo daily for 24 months.. Disposition index (DI), as an estimate of β-cell function, was calculated as the product of Homeostasis Model Assessment 2 indices derived from C-peptide values (HOMA2%Scpep) and C-peptide response during the first 30 minutes of a 75-g oral glucose tolerance test (OGTT).. Mean age was 60.5 ± 9.8 years and body mass index was 31.9 ± 4.4 kg/m2. Mean serum 25(OH)D level increased from 27.9 ± 10.3 ng/mL at baseline to 54.9 ng/mL at 2 years in the vitamin D group and was unchanged (28.5 ± 10.0 ng/mL) in the placebo group. The baseline DI predicted incident diabetes independent of the intervention. In the entire cohort, there were no significant differences in changes in DI, HOMA2%Scpep, or C-peptide response between the 2 groups. Among participants with baseline 25(OH)D level <12 ng/mL, the mean percent differences for DI between the vitamin D and placebo groups was 8.5 (95% CI, 0.2-16.8).. Supplementation with vitamin D3 for 24 months did not improve an OGTT-derived index of β-cell function in people with prediabetes not selected based on baseline vitamin D status; however, there was benefit among those with very low baseline vitamin D status.

Topics: Aged; Blood Glucose; Cholecalciferol; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Incidence; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Overweight; Prediabetic State; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Vitamin D has been linked with glucose and lipid metabolism. Men with impaired gonadal function have a higher risk of metabolic syndrome and mortality, and vitamin D status may be a reversible modulator.. This work aimed to determine the effect of daily vitamin D and calcium supplementation for 150 days on glucose and lipid homeostasis in infertile men.. A single-center, double-blinded, randomized clinical trial (NCT01304927) was conducted. A total of 307 infertile men were randomly assigned (1:1) to a single dose of 300 000 IU cholecalciferol followed by 1400 IU cholecalciferol + 500 mg of calcium daily (n = 151) or placebo (n = 156) for 150 days. Reported metabolic parameters including fasting plasma glucose, glycated hemoglobin A1c, fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), fasting plasma cholesterols, and triglycerides were secondary end points. The primary end point semen quality has previously been reported.. Men receiving vitamin D supplementation improved their vitamin D status, whereas vitamin D status was aggravated in the placebo group characterized by higher serum parathyroid hormone. At the end of the trial, men receiving vitamin D supplementation had 13% lower fasting serum insulin concentrations compared with the placebo-treated group (65 vs 74 pmol/L, P = .018) and 19% lower HOMA-IR (2.2 vs 2.7, P = .025). Moreover, men in the vitamin D group had higher high-density lipoprotein (HDL) cholesterol levels (1.38 vs 1.32 mmol/L, P = .008) compared with the placebo group.. High-dose vitamin D supplementation has beneficial effects on glucose homeostasis and HDL cholesterol levels in infertile men.

Topics: Adult; Blood Glucose; Calcium; Cholecalciferol; Cholesterol, HDL; Dietary Supplements; Fasting; Glycated Hemoglobin; Humans; Infertility, Male; Insulin; Insulin Resistance; Male; Semen Analysis; Treatment Outcome; Triglycerides; Vitamin D; Vitamin D Deficiency

Many studies in dairy cows are towards calcium homeostasis and there is a lack of knowledge about the effect of vitamin D in preventing insulin resistance and improving energy balance in the transition period of dairy cows.. The trial was conducted in a commercial dairy farm with about 1500 lactating cows in Tehran province, Iran. Twenty-four Holstein cows had been randomly selected and divided into control and treatment groups. In the treatment group, 12 cows, received a single dose of 8,000,000 IU vitamin D3 intramuscularly and in the control group, 12 cows were injected placebo (distilled water) 2-8 days before the expected calving time. Blood samples were collected between 8 and 10 AM 2 h after feeding on 21 and 7 days before calving and 1,3,7,15 and 30 days after calving. 25(OH)vitamin D, insulin-like growth factor 1 (IGF-1), insulin, nonesterified fatty acid (NEFA), β-hydroxybutyric acid (BHBA), albumin, total protein, glucose, urea, triglyceride, cholesterol and aspartate amino transferase (AST) were measured by commercially available kits. The insulin resistance index was calculated.. Vitamin D3 injection significantly affected the amounts of 25(OH) vitamin D, urea, insulin and insulin resistance index (p ≤ 0.05). On the other hand, the amounts of glucose, NEFA, BHBA concentration and AST activity were higher in control group (p ≤ 0.05). Time had a significant effect on the amounts of most measured variables except IGF-1 and insulin. There were no group and time interactions for measured variables.. It seems that injection of vitamin D3 in close up period influenced lipolysis potentially modifying energy metabolism and resulted in reducing insulin resistance.

Topics: Animals; Cattle; Cattle Diseases; Cholecalciferol; Energy Metabolism; Female; Insulin Resistance; Iran; Lactation; Postpartum Period

Although approximately 50% of Chinese with type 2 diabetes mellitus (T2DM) patients have vitamin D deficiency, studies regarding vitamin D supplementation on insulin resistance (IR) have mainly focused on non-Asians. Endurance exercise training (ET) enhances insulin-mediated glucose metabolism, which plays a critical role in T2DM prevention and control. However, the combined effects of vitamin D supplementation and ET on IR in T2DM patients are unclear. The objectives of this study is to investigate the synergistic effect of vitamin D supplementation combined with exercise training intervention on IR in T2DM patients.. We propose a 3-month randomized controlled trial among 60 T2DM patients aged 40-65, newly diagnosed with T2DM ≤ 1 year, and with stable HbA1c level (≤ 8.0%) in the past 3 months. The participants will be randomly allocated to the vitamin D group, vitamin D combined with exercise training group, exercise training group, and control group (CG) using a computer-generated random number sequence. At baseline, participants will undergo a medical review, anthropometric measurements, dual X-ray absorptiometry, a 75-g oral glucose tolerance test (OGTT), ankle-brachial index measurements, and physical fitness measurements and will complete related lifestyle questionnaires. Fasting blood lipid and glucose levels were also measured. In a 3-month intervention period, vitamin D intervention group will receive a dose of 1000 IU daily; exercise group will perform a 1-h endurance exercise 3 times per week (maximal heart rate, 60-80%), and the control group will receive apparently identical tablets. Additionally, all participants will be advised to maintain their normal diet and physical activities during the intervention. All measurements will be repeated at 3-month follow-up after the intervention with the primary outcome measure expressed as a change from baseline in insulin sensitivity and secretion. Secondary outcome measures will compare the changes in anthropometry, ankle-brachial index, and physical fitness factors (e.g., peak oxygen uptake, hand grip strength). Data will be managed and analyzed using the Statistical Package for the Social Sciences.. This is the first study to conduct a randomized trial to clearly determine the independent and combined effects of vitamin D supplementation and endurance exercise trial on IR in Chinese T2DM patients as measured by OGTT. The findings from the proposed study will not only provide new evidences that vitamin D supplementation plays an important role in IR management but also develop a simple and efficient method to improve IR-associated metabolic diseases for T2DM patients.. Chinese Clinical Trial Registry ChiCTR1800015383 , Registered on 28 March 2018.

Topics: Cholecalciferol; Diabetes Mellitus, Type 2; Dietary Supplements; Exercise; Hand Strength; Humans; Insulin Resistance; Randomized Controlled Trials as Topic; Vitamin D; Vitamin D Deficiency

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world with no definite treatment. Insulin resistance (IR) and low serum vitamin D are closely linked to NAFLD. Since there is no comparative study on the effect of calcitriol with cholecalciferol on NAFLD based on homeostasis model of insulin resistance (HOMA-IR) as an IR indicator, so we designed this research.. A double blind randomized clinical trial was conducted on patients with NAFLD with concomitant vitamin D deficiency/insufficiency at two referral tertiary teaching medical centers, from July 2017 to January 2019. Patients were randomly divided into two groups: calcitriol (1 mcg/day) and cholecalciferol (50,000 IU/week) for 8 weeks. Before and after the intervention, anthropometric and laboratory data were measured and HOMA-IR was calculated for each patient.. 54 patients completed the trial. In total, calcitriol supplementation improved serum insulin levels as well as IR based on the HOMA-IR index, significantly compared to the cholecalciferol group. HOMA-IR decreased 1.8 times more in patients receiving calcitriol than in those receiving cholecalciferol, which was clinically meaningful. The observed changes were more pronounced in patients with higher baseline body mass index. Moreover, calcitriol was more associated with a significant decrease in liver enzymes and cholesterol levels comparing to cholecalciferol.. Based on the findings of this study, the use of calcitriol supplementation significantly reduced HOMA-IR as an IR indicator in NAFLD patients, compared to cholecalciferol. To confirm this findings, further studies with larger sample sizes are recommended.

Topics: Adult; Calcitriol; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin Resistance; Iran; Male; Non-alcoholic Fatty Liver Disease; Treatment Outcome; Vitamins

Vitamin D deficiency is now a recognised problem affecting multiple physiological functions. The aim of the present study was to evaluate the effect of a single dose of vitamin D3 injection on the inflammatory, muscular damage, metabolic and cardiovascular responses to an acute bout of resistance exercise (RE) in vitamin D-deficient resistance-trained males. Blood samples from fourteen vitamin D-deficient resistance-trained males were obtained during two separate trials: lower vitamin D (LVD) and higher vitamin D (HVD, after vitamin D3 injection). Metabolic, inflammatory, muscle damage and cardiovascular markers were evaluated at baseline, immediately and 1 h after RE. There were significant trial-by-time interactions for insulin and homeostatic model assessment of insulin resistance (HOMA-IR) which significantly (P < 0·05) declined for 1 h after RE in the HVD trial compared with the LVD trial. Homeostasis model assessment of β-cell function (HOMA-β) declines at 1 h post-RE in the HVD trial. There was also a time effect for blood sugar which significantly (P < 0·05) decreased and for creatine kinase, lactate dehydrogenase and IL-6 which increased significantly 1 h post-RE in both trials. There were no significant changes in other inflammatory and cardiovascular markers following both trials. A single injection of vitamin D3 improved insulin resistance and β-cell function following RE in previously vitamin D-deficient resistance-trained males. Conversely, the injection did not change muscle damage and the inflammatory response to acute RE. Intramuscular vitamin D replacement may have key implications for the promotion of glucose metabolism and lowering the risk of diabetes in vitamin D-deficient individuals.

Topics: Adult; Biomarkers; Cholecalciferol; Cross-Over Studies; Humans; Injections; Insulin Resistance; Insulin-Secreting Cells; Male; Muscle, Skeletal; Resistance Training; Treatment Outcome; Vitamin D; Vitamin D Deficiency; Young Adult

Obese children are vulnerable to vitamin D deficiency and impaired cardiovascular health; vitamin D replenishment might improve their cardiovascular health.. The aims were to determine, in vitamin D-deficient overweight and obese children, whether supplementation with vitamin D3 1000 or 2000 IU/d is more effective than 600 IU/d in improving arterial endothelial function, arterial stiffness, central and systemic blood pressure (BP), insulin sensitivity (1/fasting insulin concentration), fasting glucose concentration, and lipid profile and to explore whether downregulation of adipocytokines and markers of systemic inflammation underlies vitamin D effects.. We conducted a randomized, double-masked, controlled clinical trial in 225 10- to 18-y-old eligible children. Change in endothelial function at 6 mo was the primary outcome.. Dose-response increases in serum 25-hydroxyvitamin D concentrations were significant and tolerated without developing hypercalcemia. Changes at 3 and 6 mo in endothelial function, arterial stiffness, systemic-systolic BP, lipids, and inflammatory markers did not differ between children receiving 1000 or 2000 IU vitamin D and children receiving 600 IU. Some secondary outcomes differed between groups. Compared with the 600-IU group, central-systolic, central-diastolic, and systemic-diastolic BP was lower at 6 mo in the 1000-IU group [-2.66 (95% CI: -5.27, -0.046), -3.57 (-5.97, -1.17), and -3.28 (-5.55, -1.00) mm Hg, respectively]; insulin sensitivity increased at 3 and 6 mo and fasting glucose concentration declined at 6 mo (-2.67; 95% CI: -4.88, -0.46 mg/dL) in the 2000-IU group.. Correction of vitamin D deficiency in overweight and obese children by vitamin D3 supplementation with 1000 or 2000 IU/d versus 600 IU/d did not affect measures of arterial endothelial function or stiffness, systemic inflammation, or lipid profile, but resulted in reductions in BP and fasting glucose concentration and in improvements in insulin sensitivity. Optimization of children's vitamin D status may improve their cardiovascular health. This trial was registered at clinicaltrials.gov as NCT01797302.

Topics: Adipokines; Adolescent; Blood Glucose; Blood Pressure; Cardiovascular System; Child; Cholecalciferol; Dietary Supplements; Female; Heart; Humans; Insulin; Insulin Resistance; Male; Obesity; Overweight; Vascular Stiffness

A low serum 25-hydroxyvitamin D (25(OH) D) concentration has been associated with a higher risk of type 2 diabetes mellitus (T2DM), especially in older people. Our aim in this randomized controlled trial was to evaluate the effect of vitamin D treatment on inflammatory markers in non-obese Lebanese patients with T2DM, living in Beirut, Lebanon.. The vitamin D group showed higher blood levels of (25(OH) D) (. Six months of vitamin D supplementation led to a decrease in some inflammatory markers in patients with T2DM. Additional studies with a larger sample and a longer period are advised in this regard. This trial was registered at ClinicalTrial.gov; Identifier number: NCT03782805.

Topics: Aged; Blood Glucose; C-Reactive Protein; Cholecalciferol; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Humans; Insulin Resistance; Interleukin-6; Lebanon; Male; Tumor Necrosis Factor-alpha; Vitamin D; Vitamin D Deficiency; Vitamins

Bariatric patients often suffer from vitamin D (VD) deficiency, and both, morbid obesity and VD deficiency, are related to an adverse effect on cardiovascular disease (CVD) risk. Therefore, we assessed the change of known CVD risk factors and its associations during the first 12 months following one-anastomosis gastric bypass (OAGB).. In this secondary analysis, CVD risk factors, medical history and anthropometric data were assessed in fifty VD deficient (25-hydroxy-vitamin D (25(OH)D) <75 nmol/l) patients, recruited for a randomized controlled trial of VD supplementation. Based on previous results regarding bone-mass loss and the association between VD and CVD risk, the study population was divided into patients with 25(OH)D ≥50 nmol/l (adequate VD group; AVD) and into those <50 nmol/l (inadequate VD group; IVD) at 6 and 12 months (T6/12) postoperatively. In the whole cohort, substantial remission rates for hypertension (38%), diabetes (30%), and dyslipidaemia (41%) and a significant reduction in CVD risk factors were observed at T12. Changes of insulin resistance markers were associated with changes of total body fat mass (TBF%), 25(OH)D, and ferritin. Moreover, significant differences in insulin resistance markers between AVD and IVD became evident at T12.. These findings show that OAGB leads to a significant reduction in CVD risk factors and amelioration of insulin resistance markers, which might be connected to reduced TBF%, change in 25(OH)D and ferritin levels, as an indicator for subclinical inflammation, and an adequate VD status. REGISTERED AT CLINICALTRIALS.GOV: (Identifier: NCT02092376) and EudraCT (Identifier: 2013-003546-16).

Topics: Adult; Austria; Biomarkers; Cardiovascular Diseases; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Gastric Bypass; Heart Disease Risk Factors; Humans; Insulin Resistance; Male; Middle Aged; Obesity, Morbid; Protective Factors; Risk Assessment; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Observational studies have suggested an inverse association between low serum 25-hydroxyvitamin D [25(OH)D] concentrations and development of type 2 diabetes. High-quality trials are required to test the hypothesis that vitamin D is a direct contributor to type 2 diabetes pathogenesis.. The purpose of this double-blind randomized placebo-controlled trial was to investigate the effect of vitamin D3 supplementation on insulin resistance (IR) and β-cell function in people with prediabetes and suboptimal vitamin D status (<50 nmol/L).. Sixty-six individuals were randomly assigned to receive 3000 IU (75 µg) vitamin D3 or placebo daily for 26 wk. Compliance was monitored by pill count and change in serum 25(OH)D concentration using LC-MS. The primary endpoint was between-group difference in change in IR assessed using a 2-step euglycemic-hyperinsulinemic clamp combined with infusion of tritiated glucose. An oral-glucose-tolerance test was performed pre- and postintervention to calculate indices of β-cell function. Between-group comparisons were made using ANCOVA.. In total, 64 participants completed the study. Baseline serum 25(OH)D concentrations in the vitamin D3 and placebo group were 30.7 and 30.0 nmol/L, with status increasing by 70.5 nmol/L and 5.3 nmol/L, respectively (between-group difference in vitamin D: 65.8 nmol/L; 95% CI: 54.2, 77.3 nmol/L; P < 0.01), after supplementation. There was no difference between groups in measures of whole-body, peripheral, or hepatic IR or in any measure of glycemic control or β-cell function.. This study employed a robust assessment of IR and β-cell function and targeted a high-risk population with low 25(OH)D status at baseline and found that vitamin D3 supplementation had no effect on insulin action in people with prediabetes.This trial was registered on clinicaltrials.gov as NCT01889810.

Topics: Adult; Aged; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Prediabetic State

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).. 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.. Vitamin D supplementation had no significant effect on metabolic and endocrine parameters in PCOS with the exception of a reduced plasma glucose during OGTT.

Topics: Adult; Austria; Blood Glucose; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin; Insulin Resistance; Polycystic Ovary Syndrome; Vitamin D; Vitamins

To determine whether vitamin D3 supplementation improves insulin sensitivity, using the hyperinsulinemic-euglycemic clamp.. This single-centre, double-blind, placebo-controlled trial randomised 96 participants at high risk of diabetes or with newly diagnosed type 2 diabetes to vitamin D3 5000 IU daily or placebo for 6 months.. We assessed at baseline and 6 months: (1) primary aim: peripheral insulin sensitivity (M-value using a 2-h hyperinsulinemic-euglycemic clamp); (2) secondary aims: other insulin sensitivity (HOMA2%S, Matsuda) and insulin secretion (insulinogenic index, C-peptide area under the curve, HOMA2-B) indices using a 2-h oral glucose tolerance test (OGTT); β-cell function (disposition index: M-value × insulinogenic index); fasting and 2-h glucose post OGTT; HbA1c; anthropometry.. Baseline characteristics were similar between groups (% or mean ± s.d.): women 38.5%; age 58.7 ± 9.4 years; BMI 32.2 ± 4.1 kg/m2; prediabetes 35.8%; diabetes 20.0%; 25-hydroxyvitamin D (25(OH)D) 51.1 ± 14.2 nmol/L. At 6 months, mean 25(OH)D reached 127.6 ± 26.3 nmol/L and 51.8 ± 16.5 nmol/L in the treatment and placebo groups, respectively (P < 0.001). A beneficial effect of vitamin D3 compared with placebo was observed on M-value (mean change (95% CI): 0.92 (0.24-1.59) vs -0.03 (-0.73 to 0.67); P = 0.009) and disposition index (mean change (95% CI): 267.0 (-343.4 to 877.4) vs -55.5 (-696.3 to 585.3); P = 0.039) after 6 months. No effect was seen on other outcomes.. In individuals at high risk of diabetes or with newly diagnosed type 2 diabetes, vitamin D supplementation for 6 months significantly increased peripheral insulin sensitivity and β-cell function, suggesting that it may slow metabolic deterioration in this population.

Topics: Aged; Cholecalciferol; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Drug Administration Schedule; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Male; Middle Aged; Prediabetic State; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Low plasma 25-hydroxy-vitamin D (25OHD) is associated with polycystic ovary syndrome (PCOS). Vitamin D deficiency may contribute to the development of insulin resistance, visceral fat and low level of adiponectin which are common feature in PCOS women. This study aimed to evaluate the effect of vitamin D supplementation on insulin resistance, visceral fat, and adiponectin in hypovitaminosis D women with polycystic ovary syndrome.. In this randomized, placebo-controlled clinical trial, 44 PCOS women aged 20-38 years with plasma 25OHD <20 ng/mL were randomized in the intervention or placebo groups and followed for 8 weeks. Participants received 50,000 IU of oral vitamin D3 once weekly in the intervention group or placebo. The visceral adipose tissue, Insulin resistance (HOMA-IR), HOMA-B, QUICKI, and circulating adiponectin were compared before and after the intervention within groups using paired tests and the mean changes were analyzed between two groups by independent t-test.. Of 44 eligible participates, 36 patients (81.8%) completed the study. After 8 week intervention, vitamin D supplementation compared to the placebo group significantly decreased fasting plasma glucose (FPG) (7.67 ± 7.66 versus 1.71 ± 7.50 mg/dL, p = .001) and significantly increased homeostasis model of assessment-estimated B cell function (HOMA-B) (129.76 ± 121.02 versus 48.32 ± 128.35, p = .014), Adiponectin (5.17 ± 8.09 versus -5.29 ± 8.64 mg/dL, p = .001), and serum vitamin D level (28.24 ± 6.47 versus 3.55 ± 4.25 ng/mL, p = .001).. Vitamin D supplementation in vitamin D deficient women with PCOS, improved the FPG, HOMA-B, Adiponectin, and serum vitamin D level.

Topics: Adiponectin; Adult; Blood Glucose; Cholecalciferol; Dietary Supplements; Female; Hormone Replacement Therapy; Humans; Insulin; Insulin Resistance; Intra-Abdominal Fat; Polycystic Ovary Syndrome; Treatment Outcome; Vitamin D Deficiency; Young Adult

This study was conducted to evaluate the effects of vitamin D supplementation on the recurrence and metabolic status of patients with cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3).. This randomized, double-blind, placebo-controlled trial was carried out among 58 women diagnosed with CIN2/3. Participants were randomly assigned into 2 groups to receive either 50,000 IU vitamin D3 (n = 29) or placebo (n = 29) every 2 weeks for 6 months.. The recurrence rate of CIN1/2/3 was 18.5 and 48.1% in the vitamin D and placebo groups respectively (p = 0.02). When we excluded CIN1, the recurrence rate of CIN2/3 became nonsignificant. Vitamin D supplementation significantly decreased fasting plasma glucose (-7.8 ± 9.2 vs. -1.1 ± 8.6 mg/dL, p = 0.006) and insulin levels (-3.2 ± 4.8 vs. -0.9 ± 3.4 µIU/mL, p = 0.03), and significantly increased quantitative insulin sensitivity check index (0.01 ± 0.02 vs. 0.002 ± 0.01, p = 0.02) compared with the placebo. Additionally, there was a significant decrease in high-sensitivity C-reactive protein (-815.3 ± 1,786.2 vs. 717.5 ± 1,827.3 ng/mL, p = 0.002) and a significant increase in total antioxidant capacity (113.4 ± 137.4 vs. -53.7 ± 186.7 mmol/L, p < 0.001) following the supplementation of vitamin D compared with the placebo.. Vitamin D3 supplementation for 6 months among women with CIN2/3 had beneficial effects on CIN1/2/3 recurrence and metabolic status; however, it did not affect CIN2/3 recurrence.

Topics: Adult; Antioxidants; C-Reactive Protein; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation; Insulin Resistance; Metabolome; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Oxidative Stress; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vitamins

Combined omega-3 fatty acid and vitamin D supplementation may improve multiple sclerosis (MS) by correcting metabolic abnormalities and attenuating oxidative stress and inflammation.. This study aimed to determine the effects of ω-3 fatty acid and vitamin D cosupplementation on the disability score and metabolic status of patients with MS.. This was a randomized, placebo-controlled clinical trial with Expanded Disability Status Scale (EDSS) score and inflammation as primary outcomes and oxidative stress biomarkers and metabolic profile as secondary outcomes. Patients, aged 18-55 y, were matched for disease EDSS scores, gender, medications, BMI, and age (n = 53) and randomly received a combined 2 × 1000 mg/d ω-3 fatty acid and 50,000 IU/biweekly cholecalciferol supplement or placebo for 12 wk. The placebos were matched in colour, shape, size, packaging, smell, and taste with supplements. Fasting blood samples were collected at baseline and end of intervention to measure different outcomes. Multiple linear regression models were used to assess treatment effects on outcomes adjusting for confounding variables.. Patients taking ω-3 fatty acid plus vitamin D supplements showed a significant improvement in EDSS (β -0.18; 95% CI: -0.33, -0.04; P = 0.01), compared with placebo. Serum high-sensitivity C-reactive protein (β -1.70 mg/L; 95% CI: -2.49, -0.90 mg/L; P < 0.001), plasma total antioxidant capacity (β +55.4 mmol/L; 95% CI: 9.2, 101.6 mmol/L; P = 0.02), total glutathione (β +51.14 µmol/L; 95% CI: 14.42, 87.87 µmol/L; P = 0.007), and malondialdehyde concentrations (β -0.86 µmol/L; 95% CI: -1.10, -0.63 µmol/L; P < 0.001) were significantly improved in the supplemented group compared with the placebo group. In addition, ω-3 fatty acid and vitamin D cosupplementation resulted in a significant reduction in serum insulin, insulin resistance, and total/HDL-cholesterol, and a significant increase in insulin sensitivity and serum HDL-cholesterol concentrations.. Overall, taking ω-3 fatty acid and vitamin D supplements for 12 wk by patients with MS had beneficial effects on EDSS and metabolic status. This trial was registered at the Iranian website (www.irct.ir) for registration of clinical trials as IRCT2017090133941N20.

Topics: Adult; Analgesics; Antioxidants; C-Reactive Protein; Cholecalciferol; Cholesterol; Cholesterol, HDL; Dietary Fats; Dietary Supplements; Disability Evaluation; Disabled Persons; Fatty Acids, Omega-3; Female; Glutathione; Humans; Inflammation; Insulin; Insulin Resistance; Malondialdehyde; Multiple Sclerosis; Oxidative Stress; Vitamins

Cardiovascular Disease (CVD) and related disorders remain a leading cause of health disparities and premature death for African Americans. Hypovitaminosis D is disproportionately prevalent in African Americans and has been linked to CVD and CVD risk factors including hypertension, diabetes and obesity. Thus, hypovitaminosis D may represent a common pathway influencing CV risk factors in a select subgroup of persons. The purpose of this paper is to report the study design of a prospective eight week prospective double-blind randomized, placebo-controlled trial (n = 330 allocated 2:1 to intervention vs. control) to assess the effect of placebo vs. high-dose oral cholecalciferol (100,000 IU vitamin D3 at baseline and week 2) on 6-week change of select biologic cardiometabolic risk factors (including parathyroid hormone to assess biologic activity, pro-inflammatory/pro-thrombotic/fibrotic markers, insulin sensitivity and vitamin D metabolites) and their relationship to vitamin D administration and modification by vitamin D receptor polymorphisms in overweight, hypertensive African Americans with hypovitaminosis D. Findings from this trial will present insights into potential causal links between vitamin D repletion and mechanistic pathways of CV disease, including established and novel genomic markers.

Topics: Black or African American; Cholecalciferol; Cytokines; Double-Blind Method; Humans; Hypertension; Inflammation; Insulin Resistance; Overweight; Parathyroid Hormone; Vitamin D Deficiency; Vitamin D-Binding Protein; Vitamins

Low serum 25-hydroxyvitamin-D (25(OH)D) concentrations are associated with insulin resistance, β-cell dysfunction and type 2 diabetes. We conducted a 24-week double-blind, randomized, placebo-controlled trial to examine the effect of 28 000 IU of vitamin D. A total of 71 participants with serum 25(OH)D ≤65 nmol/L, impaired fasting glucose and elevated glycated hemoglobin were randomly assigned to receive 28 000 IU of vitamin D. Mean baseline serum 25(OH)D was 48.1 and 47.6 nmol/L in the VitD and placebo groups, respectively. Serum 25(OH)D significantly increased to 98.7 nmol/L (51 nmol/L increase; P < .0001) in the VitD group. No significant differences in fasting ( P = .42) or 2hPC glucose ( P = .55) or other indices of glucose metabolism, including β-cell function and insulin sensitivity, were observed between groups. A subgroup analysis of individuals with 25(OH)D < 50 nmol/L and prediabetes did not change these results. The VitD group exhibited a significant reduction in LDL cholesterol (-0.27 vs 0.01 mmol/L, P = .03).. Weekly doses of vitamin D

Topics: Adult; Blood Glucose; Cholecalciferol; Cholesterol, LDL; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Fasting; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Postprandial Period; Prediabetic State; Risk; Vitamin D; Vitamin D Deficiency; Vitamins

Obesity in children is associated with vitamin D deficiency and endothelial dysfunction. It is not known if treatment with vitamin D improves endothelial function in obese adolescents.. This study aimed to determine whether treatment with vitamin D3 improves endothelial function in obese adolescents.. Nineteen obese adolescents, 13-18 years of age, with 25-hydroxy vitamin D (25[OH]D) levels <75 nmol L(-1) were treated with 100 000 IU vitamin D3 orally once a month for 3 months in an open-label, single-centre prospective trial. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery at study entry and 1 month after the third dose of vitamin D3 . Biochemical parameters, including calcium, fasting lipids, glucose, insulin and high-sensitivity C-reactive protein, were also obtained.. Mean 25(OH)D levels increased from 55.9 ± 12.2 to 86.9 ± 16.7 nmol L(-1) (P < 0.01). There was no correlation between 25(OH)D levels and brachial artery FMD. The brachial artery FMD (%) did not change significantly following vitamin D3 treatment (9.5 ± 3.53 vs. 10.3 ± 3.83, P = 0.83). Serum parathyroid hormone declined from 3.8 ± 1.5 to 3.1 ± 1 pmol L(-1) (P = 0.01). The remainder of biochemical measurements did not show a significant change.. Treatment with vitamin D3 , 100 000 IU once a month for 3 months was effective in increasing 25(OH)D levels in obese adolescents but did not impact endothelial function.

Topics: Adolescent; Brachial Artery; C-Reactive Protein; Calcium; Cholecalciferol; Endothelium, Vascular; Female; Humans; Insulin; Insulin Resistance; Lipids; Male; Parathyroid Hormone; Pediatric Obesity; Prospective Studies; Vitamin D; Vitamin D Deficiency

The present study was designed to examine the effects of vitamin D plus calcium administration on metabolic profiles and pregnancy outcomes among women at risk for pre-eclampsia.. In a prospective, double-blind, placebo-controlled trial, 60 women at risk for pre-eclampsia were randomised to take either 50 000 IU vitamin D3 every 2 weeks plus 1000 mg day(-1) calcium supplements (as calcium carbonate) (n = 30) or to receive placebos at the same times (n = 30) from 20 to 32 weeks of gestation. Fasting blood samples were taken at baseline and 12 weeks after intervention to determine related variables. Newborn anthropometric measurements were determined.. Taking combined cholecalciferol and calcium supplements, compared to placebo, led to significant reductions in fasting plasma glucose (FPG) [mean (SD)] [-5.7 (5.5) versus -0.6 (12.6) mg dL(-1) , P = 0.04], serum insulin concentrations [-2.8 (6.0) versus +7.7 (9.8) μIU mL(-1) , P < 0.001], homeostasis model of assessment-insulin resistance [-0.8 (1.3) versus +1.6 (2.2), P < 0.001], homeostatic model assessment-beta cell function [-8.2 (25.8) versus +32.6 (41.3, P < 0.001] and a significant rise in quantitative insulin sensitivity check index score [+0.02 (0.02) versus -0.02 (0.02, P < 0.001]. Additionally, pregnant women who received cholecalciferol plus calcium supplements had increased serum high-density lipoprotein (HDL)-cholesterol [+4.6 (8.3) versus -2.9 (7.7) mg dL(-1) , P = 0.001] and plasma total glutathione (GSH) concentrations [+23.4 (124.0) versus -94.8 (130.2) μm, P = 0.001] compared to placebo. However, after adjustment for the baseline levels, maternal age and baseline body mass index, the effects on FPG levels (P = 0.13) and systolic blood pressure (P = 0.13) disappeared.. Vitamin D plus calcium administration for 12 weeks had beneficial effects on glycaemic status, HDL-cholesterol, GSH and blood pressure among women at risk for pre-eclampsia.

Topics: Adolescent; Adult; Biomarkers; Calcium Carbonate; Calcium, Dietary; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation Mediators; Insulin Resistance; Iran; Maternal Nutritional Physiological Phenomena; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Premature Birth; Prevalence; Risk; Young Adult

There has been conflicting evidence regarding the potential role of vitamin D in glucose homeostasis. This study was designed to investigate the effect of high-dose vitamin D3 treatment on β-cell function, insulin sensitivity, and glucose tolerance in subjects with prediabetes or diet-treated type 2 diabetes.. Subjects (n = 44) were randomized to 30,000 IU vitamin D3 once weekly or placebo for 8 weeks. Hyperglycemic clamp assessed first-phase (0-12 min) and second-phase (12-120 min) insulin response, insulin sensitivity, and disposition index (DI). An oral glucose tolerance test assessed glucose tolerance and glycosylated hemoglobin assessed glycemic control.. A total of 21 (vitamin D) and 22 (placebo) subjects completed the study, respectively. Season-adjusted 25-OH-vitamin D [25(OH)D] levels were doubled in the active treated group (43-82 nmol/L). No effect of vitamin D treatment, compared with placebo, was seen on first-phase or second-phase insulin secretion. There were no group differences in insulin sensitivity, DI, or any measures of glycemic control. No hypercalcemia or other adverse effects of vitamin D treatment were seen compared with placebo. Subgroup analyses of those with the lowest basal and greatest increase in 25(OH)D levels did not change these results.. This study gives no support for any substantial effect of high-dose vitamin D treatment for 8 weeks in prediabetes or diet-treated type 2 diabetes on β-cell function, insulin sensitivity, or glycemic control.

Topics: Aged; Blood Glucose; Cholecalciferol; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Homeostasis; Humans; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Prediabetic State; Vitamins

Our study aimed to examine the effects of daily consumption of vitamin D3-supplemented yogurt (VDY) drink on insulin resistance and lipid profiles in pregnant gestational diabetes mellitus (GDM) patients.. Participants aged 24-32 years in their second trimester were randomly assigned to consume either plain yogurt or VDY daily for 16 weeks. Metabolic and lipid profiles including levels of fasting plasma glucose (FPG), serum insulin, triacylglycerol (TAG), total cholesterol (TC) and low-density lipoprotein (LDL) were assessed at baseline (week 0) and end of trial (week 16).. After 16 weeks of intervention, insulin-related variables including FPG and serum insulin levels were markedly lower in VDY group participants. Insulin resistance parameters, such as homeostasis model of assessment of insulin resistance and β cell function, were also significantly reduced in VDY group participants. Moreover, levels of TAG, TC and LDL, as well as the TC to high-density lipoprotein ratio, had also significantly decreased in the VDY group.. Daily consumption of VDY drink improves insulin resistance and lipid profiles in women with GDM.

Topics: Adult; Beverages; Biomarkers; Calcifediol; China; Cholecalciferol; Diabetes, Gestational; Double-Blind Method; Female; Food, Fortified; Humans; Hyperglycemia; Hyperinsulinism; Hyperlipidemias; Insulin Resistance; Lipids; Maternal Nutritional Physiological Phenomena; Patient Dropouts; Pregnancy; Pregnancy Trimester, Second; Yogurt; Young Adult

It is unclear whether and at what dose vitamin D supplementation affects insulin resistance (IR).. We sought to investigate whether vitamin D at doses higher than currently recommended decreases indexes of IR in an ambulatory population of overweight elderly subjects.. This double-blind, randomized, controlled multicenter trial enrolled 257 elderly overweight individuals aged ≥65 y with baseline 25-hydroxyvitamin D [25(OH)D] concentrations between 10 and 30 ng/mL. All subjects received 1000 mg calcium citrate/d, with vitamin D administered weekly at an equivalent dose of 600 or 3750 IU/d. The homeostasis model assessment (HOMA) of IR index at 1 y was the primary outcome. We also assessed the McAuley index.. In total, 222 subjects (55% women) with a mean ± SD age and body mass index (BMI; in kg/m(2)) of 71 ± 4 y and 30 ± 4, respectively, completed the study. Subjects' baseline characteristics, including IR indexes, were similar across groups: 69% had prediabetes, 54% had hypertension (47% were taking antihypertensive medications), and 60% had hyperlipidemia, nearly half of whom were receiving lipid-lowering drugs. At 1 y, mean ± SD serum 25(OH)D increased from 20 ± 7 to 26 ± 7 ng/mL in the low-dose arm (P < 0.0001) and from 21 ± 8 to 36 ± 10 ng/mL in the high-dose arm (P < 0.001). Median HOMA-IR indexes did not change compared with baseline concentrations and were similar in the high- [2.2 (IQR: 1.5, 2.9)] and low-dose [2.3 (IQR: 1.6, 3.3] treatment groups. Adjusted analyses showed that HOMA-IR was predicted by the baseline HOMA index and BMI but not by vitamin D dose, baseline serum 25(OH)D, or change in 25(OH)D.. Vitamin D3 at 3750 IU/d did not improve HOMA-IR compared with the Institute of Medicine Recommended Dietary Allowance of 600 IU/d in elderly overweight individuals. This trial was registered at clinicaltrials.gov as NCT01315366.

Topics: Aged; Body Mass Index; Cholecalciferol; Comorbidity; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin Resistance; Male; Obesity; Overweight; Vitamin D; Vitamin D Deficiency; Vitamins

Topics: Adult; Blood Glucose; Cholecalciferol; Dietary Supplements; Double-Blind Method; Fasting; Female; Humans; Insulin; Insulin Resistance; Japan; Male; Middle Aged; Reference Values; Vitamin D

Low 25-hydroxyvitamin D levels are common in patients with chronic fatigue syndrome; such patients also manifest impaired vascular health. We tested whether high-dose intermittent oral vitamin D therapy improved markers of vascular health and fatigue in patients with chronic fatigue syndrome.. Parallel-group, double-blind, randomised placebo-controlled trial. Patients with chronic fatigue syndrome according to the Fukuda (1994) and Canadian (2003) criteria were randomised to receive 100,000 units oral vitamin D3 or matching placebo every 2 months for 6 months. The primary outcome was arterial stiffness measured using carotid-femoral pulse wave velocity at 6 months. Secondary outcomes included flow-mediated dilatation of the brachial artery, blood pressure, cholesterol, insulin resistance, markers of inflammation and oxidative stress, and the Piper Fatigue scale. As many as 50 participants were randomised; mean age 49 (SD 13) years, mean baseline pulse wave velocity 7.8 m/s (SD 2.3), mean baseline office blood pressure 128/78 (18/12) mmHg and mean baseline 25-hydroxyvitamin D level 46 (18) nmol/L. 25-hydroxyvitamin D levels increased by 22 nmol/L at 6 months in the treatment group relative to placebo. There was no effect of treatment on pulse wave velocity at 6 months (adjusted treatment effect 0.0 m/s; 95% CI -0.6 to 0.6; p = 0.93). No improvement was seen in other vascular and metabolic outcomes, or in the Piper Fatigue scale at 6 months (adjusted treatment effect 0.2 points; 95% CI -0.8 to 1.2; p = 0.73).. High-dose oral vitamin D3 did not improve markers of vascular health or fatigue in patients with chronic fatigue syndrome.. www.controlled-trials.com, ISRCTN59927814.

Topics: Adult; Biomarkers; Blood Pressure; Brachial Artery; Canada; Cardiovascular Physiological Phenomena; Cholecalciferol; Cholesterol; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Fatigue Syndrome, Chronic; Female; Humans; Inflammation; Insulin Resistance; Male; Middle Aged; Oxidative Stress; Pulse Wave Analysis; Treatment Outcome; Vascular Stiffness; Vitamin D Deficiency

The effect of vitamin D supplementation and caloric restriction (CR) on glycemic indices and osteocalcin (OC) is not clear. In this randomized controlled double blind trial, we examined whether vitamin D3 supplementation at 2500 IU/d (D) or placebo has differential effects on markers of insulin sensitivity and bone turnover in overweight/obese postmenopausal women during 6 weeks of caloric restriction (weight loss; WL, n = 39) compared to weight maintenance (WM, n = 37). Seventy-six women (57 ± 6 years) completed this study and the WL groups lost 4 ± 1% of body weight. Baseline serum 25-hydroxyvitamin D (25OHD) was 24.8 ± 5.6 ng/mL at baseline; the rise was greatest in WL-D group (p < 0.05). There was an interaction between vitamin D intake and weight on serum OC, insulin, glucose and markers of insulin sensitivity (p < 0.05). The change in OC was explained by changes in serum 25OHD and insulin (model R(2) = 25.6%). Overall, vitamin D supplementation and CR influence serum osteocalcin levels and modestly favor improvements in insulin sensitivity.

Topics: Aged; Body Weight; Caloric Restriction; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Glycemic Index; Humans; Insulin Resistance; Middle Aged; Obesity; Osteocalcin; Overweight; Postmenopause

There is increasing interest in the extraskeletal effects of vitamin D, particularly in the obese state with regard to the development of insulin resistance and diabetes.. The objective of the study was to determine the effect of 2 doses of cholecalciferol (vitamin D3) supplementation on insulin action (Si) and pancreatic β-cell function in obese adolescents.. We performed a 12-wk double-blind, randomized comparison of the effect of vitamin D3 supplementation on Si and β-cell function in obese Caucasian adolescents (body mass index > 95(th) percentile). The subjects were randomly assigned to receive either 400 IU/d (n = 25) or 2000 IU/d (n = 26) of vitamin D3. Each subject underwent a 7-sample 75 g oral glucose tolerance test, with glucose, insulin, and C-peptide measurements, to calculate Si and β-cell function as assessed by the disposition index (DI), with use of the oral minimal model before and after supplementation. A total of 51 subjects aged 15.0 ± 1.9 y were enrolled. Included for analysis at follow-up were a total of 46 subjects (20 male and 26 female adolescents), 23 in each group.. Initial serum 25-hydroxyvitamin D [25(OH)D] was 24.0 ± 8.1 μg/L. There was no correlation between 25(OH)D concentrations and Si or DI. There was a modest but significant increase in 25(OH)D concentration in the 2000 IU/d group (3.1 ± 6.5 μg/L, P = 0.04) but not in the 400 IU/d group (P = 0.39). There was no change in Si or DI following vitamin D3 supplementation in either of the treatment groups (all P > 0.10).. The current study shows no effect from vitamin D3 supplementation, irrespective of its dose, on β-cell function or insulin action in obese nondiabetic adolescents with relatively good vitamin D status. Whether obese adolescents with vitamin D deficiency and impaired glucose metabolism would respond differently to vitamin D3 supplementation remains unclear and warrants further studies. This trial was registered at clinicaltrials.gov as NCT00858247.

Topics: Adolescent; Blood Glucose; Body Mass Index; Child; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Follow-Up Studies; Healthy Volunteers; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Obesity; Prospective Studies; Treatment Outcome; Vitamins

Despite Australia's sunny climate, low vitamin D levels are increasingly prevalent. Sun exposure is limited by long working hours, an increase in time spent indoors, and sun protection practices, and there is limited dietary vitamin D fortification. While the importance of vitamin D for bone mineralization is well known, its role as a protective agent against chronic diseases, such as type 2 diabetes and cardiovascular disease, is less understood. Observational and limited intervention studies suggest that vitamin D might improve insulin sensitivity and secretion, mainly via its anti-inflammatory properties, thereby decreasing the risk of development and progression of type 2 diabetes. The primary aim of this trial is to investigate whether improved plasma concentrations of 25-hydroxyvitamin D (25(OH)D), obtained through vitamin D supplementation, will increase insulin sensitivity and insulin secretion. A secondary aim is to determine whether these relationships are mediated by a reduction in underlying subclinical inflammation associated with obesity.. Fifty overweight but otherwise healthy nondiabetic adults between 18 and 60 years old, with low vitamin D levels (25(OH)D < 50 nmol/l), will be randomly assigned to intervention or placebo. At baseline, participants will undergo a medical review and anthropometric measurements, including dual X-ray absorptiometry, an intravenous glucose tolerance test, muscle and fat biopsies, a hyperinsulinemic euglycemic clamp, and questionnaires assessing diet, physical activity, sun exposure, back and knee pain, and depression. The intervention group will receive a first dose of 100,000 IU followed by 4,000 IU vitamin D (cholecalciferol) daily, while the placebo group will receive apparently identical capsules, both for a period of 16 weeks. All measurements will be repeated at follow-up, with the primary outcome measure expressed as a change from baseline in insulin sensitivity and secretion for the intervention group compared with the placebo group. Secondary outcome measures will compare changes in anthropometry, cardiovascular risk factors, and inflammatory markers.. The trial will provide much needed clinical evidence on the impact of vitamin D supplementation on insulin resistance and secretion and its underlying mechanisms, which are relevant for the prevention and management of type 2 diabetes.. Clinicaltrials.gov ID: NCT02112721 .

Topics: Adolescent; Adult; Biomarkers; Cholecalciferol; Clinical Protocols; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Inflammation Mediators; Insulin; Insulin Resistance; Male; Middle Aged; Overweight; Research Design; Surveys and Questionnaires; Time Factors; Treatment Outcome; Victoria; Vitamin D; Vitamin D Deficiency; Young Adult

There is an abnormal increase in TGF-β1 bioavailability in women with polycystic ovary syndrome (PCOS), which might play a role in the pathophysiology of this syndrome. Vitamin D (VD) supplementation improves various clinical manifestations of PCOS and decreases TGF-β1 levels in several diseases including myelofibrosis.. The objective of the study was to determine the effect of VD supplementation on TGF-β1 bioavailability in VD-deficient women with PCOS and assess whether changes in TGF-β1/soluble endoglin (sENG) levels correlate with an improvement in PCOS clinical manifestations.. This was a prospective, randomized, placebo-controlled trial.. The study was conducted at an academic-affiliated medical center.. Sixty-eight VD-deficient women with PCOS who were not pregnant or taking any exogenous hormones were recruited between October 2013 and January 2015.. Forty-five women received 50 000 IU of oral vitamin D3 and 23 women received oral placebo once weekly for 8 weeks.. Serum TGF-β1, sENG, lipid profile, testosterone, dehydroepiandrosterone sulfate, and insulin resistance were measured. The clinical parameters were evaluated before and 2 months after treatment.. The VD level significantly increased and normalized after VD supplementation (16.3 ± 0.9 [SEM] to 43.2 ± 2.4 ng/mL; P < .01), whereas it did not significantly change after placebo. After the VD supplementation, there was a significant decrease in the following: the interval between menstrual periods (80 ± 9 to 60 ± 6 d; P = .04), Ferriman-Gallwey score (9.8 ± 1.5 to 8.1 ± 1.5; P < .01), triglycerides (138 ± 22 to 117 ± 20 mg/dL; P = .03), and TGF-β1 to sENG ratio (6.7 ± 0.4 to 5.9 ± 0.4; P = .04). In addition, the ΔTGF-β1 to sENG ratio was positively correlated with Δtriglycerides (r = 0.59; P = .03).. VD supplementation in VD-deficient women with PCOS significantly decreases the bioavailability of TGF-β1, which correlates with an improvement in some abnormal clinical parameters associated with PCOS. This is a novel mechanism that could explain the beneficial effects of VD supplementation in women with PCOS. These findings may support new treatment modalities for PCOS, such as the development of anti-TGF-β drugs.

Topics: Adolescent; Adult; Antigens, CD; Biological Availability; Cholecalciferol; Dehydroepiandrosterone Sulfate; Endoglin; Female; Humans; Insulin Resistance; Lipids; Polycystic Ovary Syndrome; Prospective Studies; Receptors, Cell Surface; Socioeconomic Factors; Testosterone; Transforming Growth Factor beta1; Vitamin D; Vitamin D Deficiency; Vitamins; Young Adult

To investigate the effects of vitamin D supplement for three months on anthropometric and glucose homeostatic measures in Thai adults with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT).. Forty-seven IFG and/or IGT subjects enrolled in the study. Subjects were randomized into three groups, control (n = 18), vitamin D₂ (20,000 IU weekly, n = 19) or vitamin D₃ (15,000 IU weekly, n = 10). Anthropometric variables were obtained at baseline and at 3-month. Oral glucose tolerance test was performed at baseline and at 3-month. Total serum 25(OH)D, 25(OH)D₃, and 25(OH)D2 were measured by LC-MS/MS. Insulin resistance (HOMA-IR) and insulin secretion index (HOMA%B) were calculated by the homeostasis model assessment.. The total 25(OH)D levels significantly increased from baseline in both the vitamin D₂ and the vitamin D₃ groups, while there was no change in the control group. D₃ supplementation raised 25(OH)D₃ significantly (+13.7 ± 4.9 ng/mL, p < 0.01) while D2 increased 25(OH)D2 levels (+25.9?4.2 ng/mL, p<0.001) but with a decrease in 25(OH)D3 (-13.1?3.1 ng/mL, p<0. 001). Subjects were classified into two groups, i.e., control (n = 18) and D₂ or D₃ supplementations (n = 29). After three months, waist circumference (WC) significantly decreased in subjects of vitamin D supplementation group. Body weight (BW p = 0.05), systolic blood pressure (SBP, p = 0.05), body mass index (BM, p = 0.06), and HOMA-IR (p = 0.09) also tended to decrease. Subjects with an increase of total 25(OH)D levels > 10 ng/mL (23 of 29 subjects) had significant decrease in HOMA-IR and increase in disposition index. Using robust regression analysis, we found the use of D3 was associated with a larger decrease in WC (coefficient = -3.5, p < 0.001) independent of the change in total 25(OH)D and baseline BMI. No difference between D₂ and D₃ was observed for other metabolic measures.. Weekly supplementations of vitamin D₂ (20,000 IU) or vitamin D₃ (15,000 IU) improve metabolic phenotypes in subjects with prediabetes. D₃ supplement may decrease waist circumference more than D₂ supplement.

Topics: Adult; Anthropometry; Asian People; Biological Availability; Calcifediol; Cholecalciferol; Dietary Supplements; Drug Monitoring; Ergocalciferols; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Male; Middle Aged; Phenotype; Prediabetic State; Regression Analysis; Tandem Mass Spectrometry; Treatment Outcome; Vitamins

Epidemiologic studies have shown that low vitamin D levels are associated with reduced insulin sensitivity and increased risk of developing type 2 diabetes mellitus (T2DM). However, there is little evidence that vitamin D supplementation improves glucose intolerance. We evaluated the glucose-lowering effect of vitamin D in Korean T2DM subjects. We enrolled 158 T2DM patients who had stable glycemic control [hemoglobin A1c (HbA1c) <8.5%] and vitamin D levels less than 20 ng/mL. The participants were randomized into two groups: Placebo (100 mg daily of elemental calcium administered twice a day) or Vitamin D (1000 IU daily of cholecalciferol combined with 100 mg of elemental calcium administered twice a day). We compared outdoor physical activity, glycemic control, homeostasis model of assessment - insulin resistance (HOMA-IR), and parathyroid hormone (PTH), during the 24-week intervention. We analyzed the data of 129 participants (placebo =65, vitamin D =64) who completely followed the protocol. Outdoor physical activity and oral anti-diabetic drugs did not differ between the groups. While there were significant differences in the vitamin D levels (15.6 ± 7.1 ng/mL vs 30.2 ± 10.8 ng/mL, P<0.001) and change in PTH levels (1.4 ± 15.3 pg/mL vs -5.5 ± 9.8 pg/mL, P=0.003) between the placebo and vitamin D groups, there were no differences in HbA1c (7.27 ± 0.87% vs 7.40 ± 0.90%) (P=0.415) and HOMA-IR. Serum calcium and kidney function results showed that the vitamin D supplementation was safe. While vitamin D supplementation is safe and effective in the attainment of vitamin D sufficiency, it had no effect on long-term glycemic control for T2DM in our study.

Topics: Adult; Aged; Blood Glucose; Calcium; Calcium, Dietary; Cholecalciferol; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Insulin Resistance; Male; Middle Aged; Parathyroid Hormone; Republic of Korea; Vitamin D Deficiency

To determine the effects of high-dose vitamin D on insulin sensitivity in polycystic ovary syndrome (PCOS).. Randomized, placebo-controlled trial.. Academic medical center.. Twenty-eight women with PCOS.. Vitamin D3, 12,000 IU, or placebo daily for 12 weeks.. The primary outcome was quantitative insulin sensitivity check index. Secondary outcomes included glucose and insulin levels during a 75-g oral glucose tolerance test and blood pressure.. Twenty-two women completed the study. Compared with placebo, vitamin D significantly increased 25-hydroxyvitamin D (mean [95% confidence interval] in vitamin D group 20.1 [15.7 to 24.5] ng/mL at baseline and 65.7 [52.3 to 79.2] ng/mL at 12 weeks; placebo 22.5 [18.1 to 26.8] ng/mL at baseline and 23.8 [10.4 to 37.2] ng/mL at 12 weeks). There were no significant differences in quantitative insulin sensitivity check index and other measures of insulin sensitivity; however, we observed trends toward lower 2-hour insulin and lower 2-hour glucose. We also observed a protective effect of vitamin D on blood pressure.. In women with PCOS, insulin sensitivity was unchanged with high-dose vitamin D, but there was a trend toward decreased 2-hour insulin and a protective effect on blood pressure.. NCT00907153.

Topics: Academic Medical Centers; Adolescent; Adult; Biomarkers; Blood Glucose; Blood Pressure; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Middle Aged; Pennsylvania; Pilot Projects; Polycystic Ovary Syndrome; Time Factors; Treatment Outcome; Vitamins; Young Adult

Vitamin D (D₃) status is reported to correlate negatively with insulin production and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). However, few placebo-controlled intervention data are available. We aimed to assess the effect of large doses of parenteral D3 on glycosylated haemoglobin (HbA(₁c)) and estimates of insulin action (homeostasis model assessment insulin resistance: HOMA-IR) in patients with stable T2DM.. We performed a prospective, randomised, double-blind, placebo-controlled pilot study at a single university care setting in Switzerland. Fifty-five patients of both genders with T2DM of more than 10 years were enrolled and randomised to either 300,000 IU D₃ or placebo, intramuscularly. The primary endpoint was the intergroup difference in HbA(₁c) levels. Secondary endpoints were: changes in insulin sensitivity, albuminuria, calcium/phosphate metabolism, activity of the renin-aldosterone axis and changes in 24-hour ambulatory blood pressure values.. After 6 months of D₃ supply, there was a significant intergroup difference in the change in HbA(₁c) levels (relative change [mean ± standard deviation] +2.9% ± 1.5% in the D₃ group vs +6.9% ± 2.1% the in placebo group, p = 0.041) as HOMA-IR decreased by 12.8% ± 5.6% in the D₃ group and increased by 10% ± 5.4% in the placebo group (intergroup difference, p = 0.032). Twenty-four-hour urinary albumin excretion decreased in the D₃ group from 200 ± 41 to 126 ± 39, p = 0.021). There was no significant intergroup difference for the other secondary endpoints.. D₃ improved insulin sensitivity (based on HOMA-IR) and affected the course of HbA(₁c) positively compared with placebo in patients with T2DM.

Topics: Aged; Albuminuria; Blood Pressure; Calcitriol; Calcium; Cholecalciferol; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glycated Hemoglobin; Homeostasis; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Parathyroid Hormone; Phosphates; Pilot Projects; Prospective Studies; Vitamins

Vitamin D deficiency in pregnancy is associated with an increased risk of gestational diabetes mellitus (GDM) and neonatal vitamin D deficiency. We conducted a double-blind, randomized controlled trial of low-dose (LD) versus high-dose (HD) vitamin D supplementation to investigate the effects of vitamin D supplementation on glucose metabolism during pregnancy.. Women with plasma 25-hydroxyvitamin D (25OHD) levels <32 ng/mL before 20 weeks' gestation were randomized to oral vitamin D3 at 5,000 IU daily (HD) (n = 89) or the recommended pregnancy dose of 400 IU daily (LD) (n = 90) until delivery. The primary end point was maternal glucose levels on oral glucose tolerance test (OGTT) at 26-28 weeks' gestation. Secondary end points included neonatal 25OHD, obstetric and other neonatal outcomes, and maternal homeostasis model assessment of insulin resistance. Analysis was by intention to treat.. There was no difference in maternal glucose levels on OGTT. Twelve LD women (13%) developed GDM versus seven (8%) HD women (P = 0.25). Neonatal cord 25OHD was higher in HD offspring (46 ± 11 vs. 29 ± 12 ng/mL, P < 0.001), and deficiency was more common in LD offspring (24 vs. 10%, P = 0.06). Post hoc analysis in LD women showed an inverse relationship between pretreatment 25OHD and both fasting and 2-h blood glucose level on OGTT (both P < 0.001). Baseline 25OHD remained an independent predictor after multiple regression analysis.. HD vitamin D supplementation commencing at a mean of 14 weeks' gestation does not improve glucose levels in pregnancy. However, in women with baseline levels <32 ng/mL, 5,000 IU per day was well tolerated and highly effective at preventing neonatal vitamin D deficiency.

Topics: Adult; Cholecalciferol; Diabetes, Gestational; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Fasting; Female; Glucose; Glucose Tolerance Test; Humans; Insulin Resistance; Pregnancy; Pregnancy Complications; Vitamin D; Vitamin D Deficiency; Young Adult

Low serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with insulin resistance, the metabolic syndrome, and type 2 diabetes. Because many non-Western immigrants in the Netherlands are vitamin D deficient, obese, and at high risk of diabetes, vitamin D supplementation may contribute to prevent diabetes and insulin resistance.. We examined the effect of vitamin D supplementation on insulin sensitivity and β cell function in overweight, vitamin D-deficient, non-Western immigrants at high risk of diabetes.. The study was a 16-wk, randomized, placebo-controlled trial. A total of 130 non-Western immigrants with prediabetes (fasting glucose concentration >5.5 mmol/L or random glucose concentration from 7.8 to 11.1 mmol/L) and vitamin D deficiency (serum 25[OH]D concentration <50 nmol/L) were randomly assigned after stratification by sex to receive either cholecalciferol (1200 IU/d) or a placebo for 16 wk. All participants received 500 mg Ca/d as calcium carbonate. The primary outcome was the difference in the area under the curve of insulin and glucose after a 75-g oral-glucose-tolerance test after 4 mo of treatment. Secondary outcomes were insulin-sensitivity variables, β cell-function variables, and metabolic syndrome.. Mean serum 25(OH)D concentrations increased significantly in the vitamin D compared with placebo groups. After 4 mo of therapy, the mean between-group difference was 38 nmol/L (95% CI: 32.1, 43.9 nmol/L; P < 0.001). There was no significant effect on insulin sensitivity and β cell function. In a post hoc analysis, when patients with diabetes at baseline were excluded, a significant increase in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L (P = 0.040).. Vitamin D supplementation in non-Western vitamin D-deficient immigrants with prediabetes did not improve insulin sensitivity or β cell function or change the incidence of metabolic syndrome. However, after the exclusion of diabetic subjects, an improvement in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L. This trial was registered at trialregister.nl as NTR1827.

Topics: Adult; Aged; Blood Glucose; Body Mass Index; Cholecalciferol; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Emigrants and Immigrants; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Netherlands; Obesity; Overweight; Prediabetic State; Prevalence; Risk Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency; Young Adult

In observational studies, low serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with insulin resistance and other risk factors for cardiovascular disease.. We present 1-year data from an ongoing 5-year trial in 511 individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) randomly assigned to 20,000 IU/week vitamin D3 or placebo. An oral glucose tolerance test was performed at baseline and after 1 year.. Mean baseline serum 25(OH)D was 59.9 nmol/L and 61.1 nmol/L in the vitamin D and placebo groups, respectively, and increased by 45.8 nmol/L and 3.4 nmol/L, respectively. With adjustment for baseline concentrations, no differences in measures of glucose metabolism, insulin secretion or sensitivity, blood pressure, or hs-CRP were found after 1 year. There was a slight, but significant decrease in total and LDL cholesterol in the vitamin D group compared with the placebo group, but as there was also a decrease in HDL cholesterol, the change in the total/HDL cholesterol ratio did not differ significantly. Only analyzing subjects with 25(OH)D <50 nmol/L did not change the results.. This study shows that vitamin D supplementation does not improve glycemic indices, blood pressure, or lipid status in subjects with IFG and/or IGT.

Topics: 25-Hydroxyvitamin D 2; Adult; Aged; Aged, 80 and over; Blood Pressure; Calcifediol; Cholecalciferol; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dietary Supplements; Double-Blind Method; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Lipids; Male; Middle Aged; Prediabetic State; Risk Factors; Vitamin D; Vitamin D Deficiency; Vitamins; Young Adult

To determine the effect of vitamin D3 supplementation on 25-hydroxyvitamin D [25(OH)D], lipid profile and markers of insulin resistance in obese adolescents.. In this double-blind, randomized, placebo-controlled trial, 58 obese adolescents (n = 58; 12-18 years of age) received either vitamin D3 (2,000 IU/day) or placebo for 12 weeks. Total 25(OH)D, fasting plasma glucose, insulin and lipid profile were measured at baseline and following supplementation.. The trial was completed by 44/58 enrolled participants. At the end of the 12 weeks, total serum 25(OH)D concentrations increased to a modest degree (median 6 ng/ml) in the vitamin D-supplemented group (p < 0.001). Supplementation showed no detectable changes in fasting plasma glucose, insulin, homeostatic model of assessment index (HOMA-IR), lipids and highly sensitive C-reactive protein.. 12 weeks of vitamin D3 supplementation in obese adolescents with 2,000 IU once daily resulted in a modest increase in 25(OH)D concentration in obese adolescents, but did not affect the lipid profile and markers of insulin resistance and inflammation. Further studies with higher doses of vitamin D3 and/or longer duration of supplementation are needed to understand if vitamin D3 supplementation can impact lipid profiles and markers of insulin resistance and inflammation in obese children.

Topics: Adolescent; Biomarkers; Blood Glucose; Child; Cholecalciferol; Fasting; Female; Humans; Insulin; Insulin Resistance; Lipids; Male; Obesity; Pilot Projects; Prospective Studies; Vitamins

Vitamin D insufficiency is common in subjects with type 2 diabetes. Observational studies suggest that vitamin D plays a role in the pathogenesis of type 2 diabetes. However, results of intervention studies have been inconsistent. We investigated the effects of improving vitamin D status on insulin sensitivity, insulin secretion, and inflammatory markers in patients with type 2 diabetes.. A double blind, randomized, placebo controlled trial was conducted. Sixteen patients with type 2 diabetes and hypovitaminosis D were recruited. Eight patients received colecalciferol and (280 μg daily for 2 weeks, 140 μg daily for 10 weeks) and 8 patients received identical placebo tablets for 12 weeks. Before and after intervention, patients underwent IVGTT, hyperinsulinemic euglycemic clamp, assessment of baseline high-frequency insulin pulsatility, glucose-entrained insulin pulsatility, DXA scans, 24-hour-ambulatory blood pressure monitorings, and fasting blood samples.. Serum-25(OH) vitamin D and serum-1,25(OH)₂ vitamin D increased significantly after 12 weeks in the intervention group (p=0.01, p=0.004). Serum-25(OH) vitamin D was also significantly higher in the vitamin D group compared to the placebo group (p=0.02) after intervention. Although no significant changes in insulin sensitivity, inflammation, blood pressure, lipid profile, or HbA1c were found, we observed borderline (p between 0.05 and 0.10) improvements of insulin secretion, in terms of c-peptide levels, first phase incremental AUC insulin and insulin secretory burst mass.. Improvement in vitamin D status does not improve insulin resistance, blood pressure, inflammation or HbA1c, but might increase insulin secretion in patients with established type 2 diabetes.

Topics: Aged; Biomarkers; C-Peptide; Calcifediol; Calcitriol; Cholecalciferol; Denmark; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation Mediators; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Kinetics; Male; Middle Aged; Seasons; Severity of Illness Index; Vitamin D Deficiency

Based on the growing evidence of risk reduction from fresh fruit and vegetable consumption and an inverse relationship between serum 25-hydroxyvitamin D (25OHD) and the risk of type 2 diabetes (T2D), we determined the benefits of regularly consuming vitamin D-enriched mushrooms in a prediabetic cohort. Exposing edible mushrooms to ultraviolet B (UVB) light increases vitamin D2 (D2) and raises serum 25OHD2 in healthy young adults; however, their benefit to deficient prediabetics and glucose metabolism remains untested.. Forty-three prediabetic, D-deficient adults (25OHD≤20 ng/ml), BMI>25 were randomized to four groups consuming daily entrées containing 100 g fresh sliced cooked mushrooms prepared by a chef for 16 weeks. Two groups were fed UVB-treated mushrooms initially containing: 600 IU D2 or 4000 IU D2; each one also received one capsule of placebo daily. Two control groups were fed untreated mushrooms and D3 dietary supplements at two label doses: 600 IU D3 and 4000 IU D3. D2 and D3 content were analyzed in mushrooms, before and after cooking and in over-the-counter supplements.. After 16 weeks, both D2-UVB-mushroom entrée doses, which were significantly lower after cooking, produced modest or no increases in 25OHD2 or total 25OHD relative to the positive control subjects who actually consumed about 1242 and 7320 IU per day of D3 (higher than stated on the label).. Unanticipated D2 cooking loss from fresh UVB mushrooms and probable low absorption and/or hydroxylation may explain the smaller increase in 25OHD2 in our prediabetic overweight/obese cohort compared with past findings in younger, healthy subjects. Moreover, no dose or vitamin D source was associated with modifying T2D risk factors.

Topics: Adult; Agaricales; Aged; Aged, 80 and over; Biological Availability; Cholecalciferol; Cooking; Diabetes Mellitus, Type 2; Dietary Supplements; Ergocalciferols; Female; Humans; Insulin Resistance; Male; Middle Aged; Prediabetic State; Ultraviolet Rays; Vitamin D Deficiency

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.. 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 randomized 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.. 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.. 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.

Topics: Calcium, Dietary; Cholecalciferol; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Insulin Resistance; Male; Middle Aged; Prospective Studies; Vascular Stiffness; Vitamin D; Vitamin D Deficiency

To examine whether combined vitamin D and calcium supplementation improves insulin sensitivity, insulin secretion, β-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 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.. 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.. 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.. Australian New Zealand Clinical Trials Registry ACTRN12609000043235.

Topics: Adiponectin; Adult; Aged; Blood Glucose; C-Peptide; C-Reactive Protein; Calcium, Dietary; Cholecalciferol; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Interleukin-6; Male; Middle Aged; Osteocalcin; Pilot Projects; Prediabetic State; Tumor Necrosis Factor-alpha; Vitamin D Deficiency

Obese adolescents are at a greater risk of vitamin D deficiency because vitamin D is thought to be sequestered by excess adipose tissue. Poor vitamin D status has been associated with a higher prevalence of the metabolic syndrome, type 2 diabetes, or both in adults and adolescents.. The objective was to determine in obese adolescents the efficacy and safety of 4000 IU vitamin D3/d and whether subsequent increased circulating concentrations of 25-hydroxyvitamin D [25(OH)D] are associated with improved markers of insulin sensitivity and resistance and reduced inflammation.. Obese adolescent patients [n = 35; mean ± SD age: 14.1 ± 2.8 y; BMI (in kg/m(2)): 39.8 ± 6.1; 25(OH)D: 19.6 ± 7.1 ng/mL] were recruited from the University of Missouri Adolescent Diabetes and Obesity Clinic and were randomly assigned to receive either vitamin D3 (4000 IU/d) or placebo as part of their standard care. Anthropometric measurements, inflammatory markers (IL-6, TNF-α, C-reactive protein), adipokines (leptin, adiponectin), fasting glucose, fasting insulin, and HOMA-IR values were measured at baseline and at 2 follow-up visits (3 and 6 mo).. After 6 mo, there were no significant differences in BMI, serum inflammatory markers, or plasma glucose concentrations between groups. Participants supplemented with vitamin D3 had increases in serum 25(OH)D concentrations (19.5 compared with 2.8 ng/mL for placebo; P < 0.001), fasting insulin (-6.5 compared with +1.2 μU/mL for placebo; P = 0.026), HOMA-IR (-1.363 compared with +0.27 for placebo; P = 0.033), and leptin-to-adiponectin ratio (-1.41 compared with +0.10 for placebo; P = 0.045). Inflammatory markers remained unchanged.. The correction of poor vitamin D status through dietary supplementation may be an effective addition to the standard treatment of obesity and its associated insulin resistance. This trial was registered at clinicaltrials.gov as NCT00994396.

Topics: Adipokines; Adiponectin; Adolescent; Blood Glucose; Body Mass Index; Child; Cholecalciferol; Dietary Supplements; Female; Humans; Inflammation Mediators; Insulin; Insulin Resistance; Leptin; Male; Obesity; Treatment Outcome; Vitamin D; Vitamin D Deficiency; Vitamins

Vitamin D deficiency is considered as a risk factor in cardiometabolic disorders, including cardiovascular diseases, hypertension and Type 2 diabetes mellitus. We have investigated the effect of vitamin D3 supplementation on glucose homeostasis in healthy overweight and obese women.. In a double-blind randomized placebo-controlled clinical trial, 77 healthy overweight or obese women (mean age 38 ± 8 years; BMI 29.9 ± 4.2 kg/m(2)) were randomly assigned to the vitamin D3 group (25 μg/day as cholecalciferol tablets) or the placebo group. Selected anthropometric indices, glucose, insulin, HbA(1c) and homeostasis model assessment of insulin resistance at baseline and after 12 weeks were measured. Dietary intakes using 24-h food recall and food frequency questionnaires were assessed. Physical activity was assessed by the International Physical Activity Questionnaire. Adjusted mean differences were calculated using analysis of covariance. Correlation coefficients were calculated by Pearson's analysis.. Mean fasting blood glucose concentrations declined in the vitamin D3 and placebo groups (-0.28 ± 0.4 vs. -0.65 ± 0.4 mmol/l, P < 0.001) and the mean percentage of HbA(1c) was decreased (-13 ± 18 vs. -19 ± 17 mmol/l, P = 0.06) in both groups, respectively. Mean 25-hydroxyvitamin D concentrations increased in the vitamin D3 and placebo groups (38.2 ± 32 vs. 4.6 ± 14 nmol/l, P < 0.001), respectively. There was a significant correlation between HbA(1c) and 25-hydroxyvitamin D concentrations (r = -0.271; P = 0.018).. The results indicate that the vitamin D3 supplement of 25 μg/day had no beneficial effect on glycaemic indices in healthy overweight or obese women.

Topics: Adult; Blood Glucose; Body Mass Index; Cholecalciferol; Diet Records; Dietary Supplements; Double-Blind Method; Eating; Exercise; Female; Homeostasis; Humans; Insulin Resistance; Male; Obesity; Surveys and Questionnaires; Treatment Outcome; Vitamin D Deficiency; Vitamins

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.

Topics: Adult; Aged; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Body Composition; Calcium Carbonate; Cholecalciferol; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hyperparathyroidism, Primary; Insulin Resistance; Male; Middle Aged; Parathyroid Hormone; Parathyroidectomy; Risk Assessment; Risk Factors; Sweden; Treatment Outcome

To our knowledge, there is no study that has examined the effects of vitamin D supplementation on metabolic status in gestational diabetes mellitus (GDM).. This study was designed to assess the effects of vitamin D supplementation on metabolic profiles, high-sensitivity C-reactive protein, and biomarkers of oxidative stress in pregnant women with GDM.. This randomized, double-blind, placebo-controlled clinical trial was conducted in 54 women with GDM. Subjects were randomly assigned to receive either vitamin D supplements or placebo. Individuals in the vitamin D group (n = 27) received capsules containing 50,000 IU vitamin D₃ 2 times during the study (at baseline and at day 21 of the intervention) and those in the placebo group (n = 27) received 2 placebos at the same times. Fasting blood samples were collected at baseline and after 6 wk of the intervention to quantify relevant variables.. Cholecalciferol supplementation resulted in increased serum 25-hydroxyvitamin D concentrations compared with placebo (+18.5 ± 20.4 compared with +0.5 ± 6.1 ng/mL; P < 0.001). Furthermore, intake of vitamin D supplements led to a significant decrease in concentrations of fasting plasma glucose (-17.1 ± 14.8 compared with -0.9 ± 16.6 mg/dL; P < 0.001) and serum insulin (-3.08 ± 6.62 compared with +1.34 ± 6.51 μIU/mL; P = 0.01) and homeostasis model of assessment-insulin resistance (-1.28 ± 1.41 compared with +0.34 ± 1.79; P < 0.001) and a significant increase in the Quantitative Insulin Sensitivity Check Index (+0.03 ± 0.03 compared with -0.001 ± 0.02; P = 0.003) compared with placebo. A significant reduction in concentrations of total (-11.0 ± 23.5 compared with +9.5 ± 36.5 mg/dL; P = 0.01) and low-density lipoprotein (LDL) (-10.8 ± 22.4 compared with +10.4 ± 28.0 mg/dL; P = 0.003) cholesterol was also seen after vitamin D supplementation.. Vitamin D supplementation in pregnant women with GDM had beneficial effects on glycemia and total and LDL-cholesterol concentrations but did not affect inflammation and oxidative stress. This trial was registered at www.irct.ir as IRCT201305115623N7.

Topics: Adult; Biomarkers; C-Reactive Protein; Calcifediol; Cholecalciferol; Diabetes, Gestational; Dietary Supplements; Double-Blind Method; Female; Humans; Hypercholesterolemia; Hyperinsulinism; Insulin Resistance; Intention to Treat Analysis; Iran; Lost to Follow-Up; Oxidative Stress; Pregnancy; Pregnancy Complications; Vitamin D Deficiency

To assess the impact of vitamin D supplementation (cholecalciferol) on the insulin sensitivity and metabolic health of patients with chronic kidney disease (CKD).. Twenty-eight adult patients with CKD stages 3-4 were recruited from the outpatient department of the Princess Alexandra Hospital (Brisbane, Australia) to a double-blind randomized trial of cholecalciferol (vitamin D3) 2000 IU/day or placebo for 6 months. Metabolic parameters at baseline were compared with 20 non-CKD adults. The primary outcome was an improvement in insulin resistance (glucose disposal rate, GDR) at 6 months (quantified by hyperinsulinaemic euglycaemic clamp). Carbohydrate and lipid oxidation rates were assessed by indirect calorimetry.. At baseline, patients were significantly insulin-resistant compared with lean younger non-CKD individuals (n = 9; GDR 3.42 vs. 5.76 mg/kg per minute, P = 0.001), but comparable with their age-, gender- and weight-matched non-CKD counterparts (n = 11; 3.42 vs. 3.98 mg/kg per minute, P = 0.4). 25-Hydroxyvitamin D did not change in the placebo group, but rose from 95 ± 37 to 146 ± 25 nmol/L with treatment (P = 0.0001). Post treatment, there was no difference in GDR between groups (GDR 3.38 vs. 3.52 mg/kg per minute, ancova P = 0.4). There was a relative increase in hyperinsulinaemic oxidative disposal of glucose with treatment (within-group P = 0.03).. Supplementation with cholecalciferol in CKD 3-4 results in appreciable increases in 25-hydroxyvitamin D concentrations, but does not increase insulin sensitivity. The insulin resistance observed was similar among age-, sex- and body mass index-matched individuals with and without CKD. Whether renal dysfunction per se has any influence on the insulin sensitivity of an individual should be the subject of future work.

Topics: Aged; Cholecalciferol; Double-Blind Method; Female; Humans; Insulin Resistance; Male; Metabolic Diseases; Renal Insufficiency, Chronic; Severity of Illness Index; Treatment Failure; Vitamins

Both altered GH-IGF-I axis and low serum levels of 25-hydroxyvitamin D (25(OH)D) are linked to measures of metabolic syndrome. Our hypothesis was that there is a relation between GH, IGF-I, and 25(OH)D; and that vitamin D supplementation may have an effect on the levels of GH, IGF-I, and IGF-I/IGFBP-3 ratio. 318 overweight and obese subjects completed a one-year randomized intervention with either 40,000 or 20,000 IU cholecalciferol per week or placebo. GH, IGF-I, IGFBP-3 and measures of insulin resistance were evaluated at baseline and at the end of study. There was a significant relation between entities of GH-IGF-I axis and insulin resistance. Subjects with severe obesity had significantly lower serum 25(OH)D and had a significant linear decline in IGF-I/IGFBP-3 ratio with increasing serum 25(OH)D quartiles. Vitamin D status was an independent predictor of GH-IGF-I axis and supplementation with vitamin D decreased IGF-I/IGFBP-3 ratio in subjects without severe obesity. No corresponding effect of vitamin D supplementation on BMI or insulin resistance was observed. Adverse effects of GH-IGF-I axis on glucose metabolism and the development of metabolic syndrome may be in part associated with the changes in vitamin D status.

Topics: Adult; Aged; Cholecalciferol; Dietary Supplements; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Glucose; Growth Hormone; Humans; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Signal Transduction

Insulin resistance is one of the most common features of polycystic ovary syndrome (PCOS). Some studies suggest that vitamin D deficiency may have a role in insulin resistance; thus, the aim of the current study was to determine the effect of vitamin D supplementation on insulin resistance in women with PCOS and a vitamin D deficiency. We hypothesized that vitamin D supplementation would lower the glucose level and insulin resistance in women with PCOS and a vitamin D deficiency. The current study was a randomized, placebo-controlled, double-blinded trial with 50 women with PCOS and a vitamin D deficiency, 20 to 40 years old, assigned to receive 3 oral treatments consisting of 50,000 IU of vitamin D₃ or a placebo (1 every 20 days) for 2 months (vitamin D, n = 24; placebo, n = 26). The fasting blood glucose, insulin, 25-hydroxyvitamin D, and parathyroid hormone levels, as well as the homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were measured at baseline and after treatment. In the vitamin D group, the serum level of 25-hydroxyvitamin D increased (6.9 ± 2.8 to 23.4 ± 6.1 ng/mL, P < .0001), and the parathyroid hormone level decreased (70.02 ± 43.04 to 50.33 ± 21.99 μ IU/mL, P = .02). There were no significant changes in the placebo group. There was a significant increase in insulin secretion in the vitamin D group (P = .01), but this was not significant compared with the placebo group. The fasting serum insulin and glucose levels and the insulin sensitivity and homeostasis model assessment of insulin resistance did not change significantly by the end of the study. We were not able to demonstrate the effect of vitamin D supplementation on insulin sensitivity and insulin resistance in women with PCOS and vitamin D deficiency.

Topics: Adult; Blood Glucose; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin; Insulin Resistance; Insulin Secretion; Parathyroid Hormone; Polycystic Ovary Syndrome; Vitamin D; Vitamin D Deficiency; Vitamins; Young Adult

Vitamin D deficiency may increase the risk for type 2 diabetes. African Americans tend to have poor vitamin D status and increased risk of diabetes, but effects of vitamin D supplementation on components of diabetes risk have not been tested in this group. This study was conducted to determine whether vitamin D supplementation improves insulin secretion, insulin sensitivity and glycaemia in African Americans with prediabetes or early diabetes.. In this randomized, placebo-controlled trial, we examined the effect of 4000 IU/day vitamin D(3,) on glycaemia and contributing measures including insulin secretion, insulin sensitivity and the disposition index over 12 weeks in 89 overweight or obese African Americans with prediabetes or early diabetes. Outcome measures were derived from oral glucose tolerance testing.. Mean plasma 25-hydroxyvitamin D was about 40 nmol/l in the placebo and vitamin D groups at baseline and increased to 81 nmol/l with supplementation. Insulin sensitivity decreased by 4% in the vitamin D group compared with a 12% increase in the placebo group (p = 0.034). Insulin secretion increased by 12% in the vitamin D group compared with a 2% increase in the placebo group (p = 0.024), but changes in the disposition index were similar across groups. There was no effect of supplementation on post-load glucose or other measures of glycaemia.. Supplementation with 4000 IU/day vitamin D(3) successfully corrected vitamin D insufficiency and had divergent effects on insulin secretion and sensitivity with no overall effect on disposition index or glycaemia. In this study, vitamin D supplementation for 3 months did not change the pathophysiology of prediabetes in overweight and obese African Americans.

Topics: Black or African American; Blood Glucose; Cholecalciferol; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Obesity; Overweight; Prediabetic State; Vitamin D; Vitamin D Deficiency; Vitamins

Insufficient vitamin D status has been linked to autoimmune diseases, cancer and metabolic disorders, like obesity and insulin resistance. In vitro and animal studies suggest that vitamin D may play a crucial role in immune activation and inflammation. The relation between vitamin D and pro-inflammatory cytokines is not completely established. Furthermore, it is not known if the effect of vitamin D on entities of metabolic syndrome is mediated through its effect on cytokines or other biomarkers. The objectives of this study were to investigate if there is a relationship between vitamin D status and such pro-inflammatory cytokines as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and high sensitive C-reactive protein (hs-CRP) in patients with overweigh and obesity. We also proposed that the intervention with high dose of cholecalciferol may have effect on the cytokine levels and result in corresponding changes in the measures of insulin resistance (HOMA-IR and QUICKI). Serum levels of IL-6, TNF-α and hs-CRP were measured in 332 overweight and obese subjects who completed a 1-year randomised intervention with either 40,000 IU vitamin D (cholecalciferol) per week or 20,000 IU vitamin D per week, or placebo. We found significant associations between IL-6, TNF-α, vitamin D and insulin resistance indices at baseline. One year intervention with vitamin D decreased serum IL-6 levels; however hs-CRP levels were significantly increased. Neither measures of insulin resistance, nor TNF-α were influenced by a 1-year vitamin D supplementation.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Cholecalciferol; Dietary Supplements; Female; Humans; Insulin Resistance; Interleukin-6; Male; Middle Aged; Obesity; Overweight; Tumor Necrosis Factor-alpha; Young Adult

Low serum concentrations of 25-hydroxyvitamin D [25(OH)D] have been associated with impaired glucose tolerance and diabetes.. This study aimed to compare the effects of daily intake of vitamin D- or vitamin D(3) + calcium-fortified yogurt drink on glycemic status in subjects with type 2 diabetes (T2D).. Ninety diabetic subjects were randomly allocated to 3 groups to consume plain yogurt drink (PY; containing no vitamin D and 150 mg Ca/250 mL), vitamin D-fortified yogurt drink (DY; containing 500 IU vitamin D(3) and 150 mg Ca/250 mL), or vitamin D + calcium-fortified yogurt drink (DCY; containing 500 IU vitamin D(3) and 250 mg Ca/250 mL) twice per day for 12 wk. Fasting serum glucose (FSG), glycated hemoglobin (Hb A(1c)), homeostasis model assessment of insulin resistance (HOMA-IR), serum lipid profile, and percentage fat mass (FM) were assessed before (baseline) and after the intervention.. In both the DY and DCY groups, mean serum 25(OH)D(3) improved (+32.8 ± 28.4 and +28.8 ± 16.1 nmol/L, respectively; P < 0.001 for both), but FSG [-12.9 ± 33.7 mg/dL (P = 0.015) and -9.6 ± 46.9 mg/dL (P = 0.035)], Hb A(1c) [-0.4 ± 1.2% (P < 0.001) and -0.4 ± 1.9% (P < 0.001)], HOMA-IR [-0.6 ± 1.4 (P = 0.001) and -0.6 ± 3.2 (P < 0.001)], waist circumference (-3.6 ± 2.7 and -2.9 ± 3.3; P < 0.001 for both), and body mass index [in kg/m(2); -0.9 ± 0.6 (P < 0.001) and -0.4 ± 0.7 (P = 0.005)] decreased significantly more than in the PY group. An inverse correlation was observed between changes in serum 25(OH)D(3) and FSG (r = -0.208, P = 0.049), FM (r = -0.219, P = 0.038), and HOMA-IR (r = -0.219, P = 0.005).. Daily intake of a vitamin D-fortified yogurt drink, either with or without added calcium, improved glycemic status in T2D patients. This trial was registered at clinicaltrials.gov as NCT01229891.

Topics: Adult; Blood Glucose; Body Composition; Body Mass Index; Calcium; Cholecalciferol; Diabetes Mellitus, Type 2; Fasting; Female; Food, Fortified; Glycated Hemoglobin; Humans; Insulin Resistance; Male; Middle Aged; Vitamin D; Vitamins; Waist Circumference; Yogurt

Vitamin D deficiency is associated with an unfavorable metabolic profile in observational studies. The intention was to compare insulin sensitivity (the primary end point) and secretion and lipids in subjects with low and high serum 25(OH)D (25-hydroxyvitamin D) levels and to assess the effect of vitamin D supplementation on the same outcomes among the participants with low serum 25(OH)D levels.. Participants were recruited from a population-based study (the Tromsø Study) based on their serum 25(OH)D measurements. A 3-h hyperglycemic clamp was performed, and the participants with low serum 25(OH)D levels were thereafter randomized to receive capsules of 20,000 IU vitamin D(3) or identical-looking placebo twice weekly for 6 months. A final hyperglycemic clamp was then performed.. The 52 participants with high serum 25(OH)D levels (85.6 ± 13.5 nmol/L [mean ± SD]) had significantly higher insulin sensitivity index (ISI) and lower HbA(1c) and triglycerides (TGs) than the 108 participants with low serum 25(OH)D (40.3 ± 12.8 nmol/L), but the differences in ISI and TGs were not significant after adjustments. After supplementation, serum 25(OH)D was 142.7 ± 25.7 and 42.9 ± 17.3 nmol/L in 49 of 51 completing participants randomized to vitamin D and 45 of 53 randomized to placebo, respectively. At the end of the study, there were no statistically significant differences in the outcome variables between the two groups.. Vitamin D supplementation to apparently healthy subjects with insufficient serum 25(OH)D levels does not improve insulin sensitivity or secretion or serum lipid profile.

Topics: Adult; Aged; Calcifediol; Capsules; Carbohydrate Metabolism, Inborn Errors; Case-Control Studies; Cholecalciferol; Dietary Supplements; Female; Glucose Clamp Technique; Glycated Hemoglobin; Glycerol Kinase; Humans; Hyperglycemia; Hypoadrenocorticism, Familial; Insulin; Insulin Resistance; Insulin Secretion; Lipids; Male; Middle Aged; Triglycerides; Vitamin D Deficiency

Recent evidence suggests that genistein aglycone may act beneficially on surrogate cardiovascular risk markers in postmenopausal women. We assessed the effects of genistein aglycone on some cardiovascular risk factors and homocysteine levels after 3-years of continued therapy in a cohort of osteopenic, postmenopausal women.. The parent study was a randomized, double-blind, placebo-controlled trial involving 389 postmenopausal women with low bone mass for 24 months. Subsequently, a subcohort (138 patients) continued therapy for an additional year. Participants received 54mg of genistein aglycone (n=71) or placebo (n=67), daily. Both arms received calcium and vitamin D(3) in therapeutic doses. Moreover, 4 weeks before randomization procedures and during our follow-up study, all patients received dietary instructions in an isocaloric fat-restricted diet. Blood lipid profiles, fasting glucose and insulin, insulin resistance (HOMA-IR), fibrinogen, osteoprotegerin (OPG) and homocysteine at baseline and after 24 and 36 months of treatment were measured. Compared to placebo, genistein significantly decreased fasting glucose and insulin, HOMA-IR, fibrinogen and homocysteine after 24 and 36 months of treatment. By contrast, isoflavone administration did not affect high-density lipoprotein cholesterol and triglycerides though serum OPG was higher in the genistein recipients. There were no differences in adverse events or discomfort between groups. Results on routine biochemical, liver function, and hematologic testing did not change over time in placebo or genistein group.. After 3-years of treatment, genistein aglycone plus calcium, vitamin D(3) and a healthy diet showed positive effects on some cardiovascular risk factors and homocysteine levels in a cohort of postmenopausal women with low bone mass.

Topics: Calcium Carbonate; Cardiovascular Diseases; Cholecalciferol; Female; Follow-Up Studies; Genistein; Homocysteine; Humans; Insulin Resistance; Lipids; Middle Aged; Osteoprotegerin; Postmenopause; Research Design; Risk Factors

Low serum 25-hydroxyvitamin D (25(OH)D) has been shown to correlate with increased risk of type 2 diabetes. Small, observational studies suggest an action for vitamin D in improving insulin sensitivity and/or insulin secretion. The objective of the present study was to investigate the effect of improved vitamin D status on insulin resistance (IR), utilising randomised, controlled, double-blind intervention administering 100 microg (4000 IU) vitamin D(3) (n 42) or placebo (n 39) daily for 6 months to South Asian women, aged 23-68 years, living in Auckland, New Zealand. Subjects were insulin resistant - homeostasis model assessment 1 (HOMA1)>1.93 and had serum 25(OH)D concentration < 50 nmol/l. Exclusion criteria included diabetes medication and vitamin D supplementation >25 microg (1000 IU)/d. The HOMA2 computer model was used to calculate outcomes. Median (25th, 75th percentiles) serum 25(OH)D(3) increased significantly from 21 (11, 40) to 75 (55, 84) nmol/l with supplementation. Significant improvements were seen in insulin sensitivity and IR (P = 0.003 and 0.02, respectively), and fasting insulin decreased (P = 0.02) with supplementation compared with placebo. There was no change in C-peptide with supplementation. IR was most improved when endpoint serum 25(OH)D reached > or = 80 nmol/l. Secondary outcome variables (lipid profile and high sensitivity C-reactive protein) were not affected by supplementation. In conclusion, improving vitamin D status in insulin resistant women resulted in improved IR and sensitivity, but no change in insulin secretion. Optimal vitamin D concentrations for reducing IR were shown to be 80-119 nmol/l, providing further evidence for an increase in the recommended adequate levels. Registered Trial No. ACTRN12607000642482.

Topics: Adult; Asia; Asian People; C-Reactive Protein; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin; Insulin Resistance; Insulin Secretion; Middle Aged; New Zealand; Nutritional Status; Vitamin D; Vitamin D Deficiency; Vitamins

Low 25-hydroxyvitamin D levels predict future cardiovascular events and are common in patients with type 2 diabetes. We compared the effect of 100,000 and 200,000 IU doses of vitamin D(3) on endothelial function, blood pressure and markers of glycaemic control in patients with type 2 diabetes.. This was a randomised, parallel group, placebo-controlled trial. Patients with type 2 diabetes and baseline 25-hydroxyvitamin D levels <100 nmol/l were enrolled from community and hospital-based diabetes clinics. Participants were assessed in a university department of clinical pharmacology and received a single oral dose of placebo or vitamin D(3) (100,000 IU or 200,000 IU) at baseline, randomly allocated via numbered bottles prepared offsite; participants and investigators were both blinded to treatment allocation. Endothelial function, office blood pressure, B-type natriuretic peptide, insulin resistance and glycosylated haemoglobin were measured at baseline, and at 8 and 16 weeks.. We randomised 61 participants to the three groups (placebo 22, 100,000 IU vitamin D(3) 19, 200,000 IU vitamin D(3) 20). There was no significant difference in the primary outcome of endothelial function at 8 weeks (placebo 5.2%, n = 22; 100,000 IU 4.3%, n = 19; 200,000 IU 4.9%, n = 17) or at 16 weeks. Insulin resistance and glycosylated haemoglobin did not improve with either dose of vitamin D(3). On covariate analysis, systolic blood pressure was significantly lower in both treatment arms than in the placebo group at 8 weeks (placebo 146.4 mmHg, 100,000 IU 141.4 mmHg [p = 0.04 vs placebo], 200,000 IU 136.8 mmHg [p = 0.03 vs placebo]). B-type natriuretic peptide levels were significantly lower in the 200,000 IU group by 16 weeks (placebo 34 pg/ml, 200,000 IU 21 pg/ml, p = 0.02). No significant excess of adverse effects was noted in the treatment arms.. High-dose vitamin D(3) improved systolic blood pressure and B-type natriuretic peptide levels, but not endothelial function, insulin resistance or glycosylated haemoglobin in patients with type 2 diabetes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Blood Pressure; Cholecalciferol; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Female; Glycated Hemoglobin; Humans; Insulin Resistance; Male; Middle Aged; Natriuretic Peptide, Brain; Treatment Outcome

To determine the short-term effect of vitamin D(3) supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men.. A double-blind randomized controlled trial was conducted at a tertiary care facility in which 100 male volunteers aged > or = 35 years received three doses of vitamin D(3) (120,000 IU each; supplemented group) fortnightly or placebo (control group). Hepatic fasting insulin sensitivity [homeostasis model assessment (HOMA), quantitative insulin-sensitivity check index, HOMA-2], postprandial insulin sensitivity [oral glucose insulin sensitivity (OGIS)], insulin secretion (HOMA%B, HOMA2-%B), lipid profile and blood pressure were measured at baseline and at 6 weeks' follow-up.. Seventy-one of the recruited subjects completed the study (35 in supplemented group, 36 in control group). There was an increase in OGIS with supplementation by per protocol analysis (P = 0.038; intention-to-treat analysis P = 0.055). The age- and baseline 25-hydroxyvitamin D level-adjusted difference in change in OGIS was highly significant (mean difference 41.1 +/- 15.5; P = 0.01). No changes in secondary outcome measures (insulin secretion, basal indices of insulin sensitivity, blood pressure or lipid profile) were found with supplementation.. The trial indicates that vitamin D(3) supplementation improves postprandial insulin sensitivity (OGIS) in apparently healthy men likely to have insulin resistance (centrally obese but non-diabetic).

Topics: Abdominal Fat; Adult; Blood Glucose; Body Fat Distribution; Cholecalciferol; Double-Blind Method; Humans; India; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Statistics as Topic; Waist-Hip Ratio

Approximately 50% of patients with stage 3 Chronic Kidney Disease are 25-hydroxyvitamin D insufficient, and this prevalence increases with falling glomerular filtration rate. Vitamin D is now recognised as having pleiotropic roles beyond bone and mineral homeostasis, with the vitamin D receptor and metabolising machinery identified in multiple tissues. Worryingly, recent observational data has highlighted an association between hypovitaminosis D and increased cardiovascular mortality, possibly mediated via vitamin D effects on insulin resistance and inflammation. The main hypothesis of this study is that oral Vitamin D supplementation will ameliorate insulin resistance in patients with Chronic Kidney Disease stage 3 when compared to placebo. Secondary hypotheses will test whether this is associated with decreased inflammation and bone/adipocyte-endocrine dysregulation.. This study is a single-centre, double-blinded, randomised, placebo-controlled trial. Inclusion criteria include; estimated glomerular filtration rate 30-59 ml/min/1.73 m(2); aged >or=18 on entry to study; and serum 25-hydroxyvitamin D levels <75 nmol/L. Patients will be randomised 1:1 to receive either oral cholecalciferol 2000IU/day or placebo for 6 months. The primary outcome will be an improvement in insulin sensitivity, measured by hyperinsulinaemic euglycaemic clamp. Secondary outcome measures will include serum parathyroid hormone, cytokines (Interleukin-1beta, Interleukin-6, Tumour Necrosis Factor alpha), adiponectin (total and High Molecular Weight), osteocalcin (carboxylated and under-carboxylated), peripheral blood mononuclear cell Nuclear Factor Kappa-B p65 binding activity, brachial artery reactivity, aortic pulse wave velocity and waveform analysis, and indirect calorimetry. All outcome measures will be performed at baseline and end of study.. To date, no randomised controlled trial has been performed in pre-dialysis CKD patients to study the correlation between vitamin D status with supplementation, insulin resistance and markers of adverse cardiovascular risk. We remain hopeful that cholecalciferol may be a safe intervention, with health benefits beyond those related to bone-mineral homeostasis.. Australian and New Zealand Clinical Trials Registry ACTRN12609000246280.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Bone Density Conservation Agents; Cholecalciferol; Double-Blind Method; Female; Humans; Inflammation; Insulin Resistance; Kidney Failure, Chronic; Male; Placebo Effect; Treatment Outcome; Vitamin D Deficiency; Young Adult

Prediabetes is a condition of intermediate hyperglycemia that may progress to type 2 diabetes. Vitamin D deficiency has been frequently linked to insulin resistance and diabetes. The study aimed to investigate the role of D supplementation and its possible mechanism of action on insulin resistance in prediabetic rats.. The study was conducted on 24 male Wistar rats that were randomly divided into 6 rats as healthy controls and 18 prediabetic rats. Prediabetic rats were induced with a high-fat and high-glucose diet (HFD-G) combined with a low dose of streptozotocin. Rats with the prediabetic condition were then randomized into three groups of 12-week treatment: one group that received no treatment, one that received vitamin D3 at 100 IU/kg BW, and one group that received vitamin D3 at 1000 IU/kg BW. The high-fat and high-glucose diets were continuously given throughout the twelve weeks of treatment. At the end of the supplementation period, glucose control parameters, inflammatory markers, and the expressions of IRS1, PPARγ, NF-κB, and IRS1 were measured.. Vitamin D3 dose-dependently improves glucose control parameters, as shown by the reduction of fasting blood glucose (FBG), oral glucose tolerance test (OGTT), glycated albumin, insulin levels, and markers of insulin resistance (HOMA-IR). Upon histological analysis, vitamin D supplementation resulted in a reduction of the islet of Langerhans degeneration. Vitamin D also enhanced the ratio of IL-6/IL-10, reduced IRS1 phosphorylation at Ser307, increased expression of PPAR gamma, and reduced phosphorylation of NF-KB p65 at Ser536.. Vitamin D supplementation reduces insulin resistance in prediabetic rats. The reduction might be due to the effects of vitamin D on IRS, PPARγ, and NF-κB expression.

Topics: Animals; Blood Glucose; Cholecalciferol; Diabetes Mellitus, Type 2; Dietary Supplements; Insulin Resistance; Male; NF-kappa B; PPAR gamma; Prediabetic State; Rats; Rats, Wistar; Vitamin D; Vitamins

Vitamin D

Topics: Animals; Calcium; Calcium Channels, L-Type; Cholecalciferol; Cyclic AMP-Dependent Protein Kinases; Exocytosis; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Islets of Langerhans; Male; Rats; Rats, Wistar

Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including central obesity, hypertension, insulin resistance, dyslipidemia, and hyperglyemia. MetS is found to be a positive predictor of cardiovascular morbidity and mortality. The present study was planned to test the efficacy of vitamin D3 supplementation as compared with cortisol inhibition on MetS parameters. Wistar rats were allocated into four groups: control, untreated MetS, and MetS treated with either vitamin D3 (10 µg/kg) or carbenoxolone (50 mg/kg). MetS was induced by combination of high-fat diet and oral fructose. After the induction period (8 weeks), MetS was confirmed, and treatment modalities started for a further 4 weeks. Compared with untreated MetS, vitamin D3- and carbenoxolone-treated rats showed significant reduction in blood pressure, body mass index, Lee index, waist circumference, retroperitoneal fat, and improvement of dyslipidemia. Meanwhile, treatment with carbenoxolone significantly lowered the elevated liver enzymes, and vitamin D3 resulted in improved insulin sensitivity, enhanced glucose uptake by muscles, and replenished glycogen content in the liver and muscles near control levels. In conclusion, although treatment with vitamin D3 or carbenoxolone reduced the risk factors associated with MetS, vitamin D3 was effective in ameliorating insulin resistance which is the hallmark of MetS.

Topics: Animals; Blood Glucose; Carbenoxolone; Cholecalciferol; Insulin Resistance; Metabolic Syndrome; Rats; Rats, Wistar

Previous studies have shown that vitamin D3 may be a potential factor in insulin resistance, but the relationship between vitamin D3 and insulin resistance still remains controversial. At present, more research is needed to explore the relationship between vitamin D3 and insulin resistance. The samples from 2009 to 2018 in NHANES database were analyzed to Investigate the relationship and the potential mechanism. We performed a cross-sectional study of five periods in the NHANES database. Finally, 9298 participants were selected through strict inclusion and exclusion criteria, Multivariate logistic regression analysis and curve fitting were conducted to explore the relationship between vitamin D3 level and insulin resistance. Moreover, subgroup analysis was used to further prove the association. The results revealed that there was a strong association between vitamin D3 and insulin resistance (OR 0.82, 95% CI 0.72-0.93). However, subgroup analyses indicated that this correlation varied between individuals and races. There was a negative correlation between vitamin D3 level and insulin resistance, which provides a new proof for exploring the influencing factors of insulin resistance. More well-designed studies are still needed to further elaborate on these associations.

Topics: Adult; Aged; Biomarkers; Blood Glucose; Cholecalciferol; Cross-Sectional Studies; Databases, Factual; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Middle Aged; Nutrition Surveys; Race Factors; Risk Assessment; Risk Factors; United States; Young Adult

Previous studies have shown that vitamin D3 (VD3) may be a protective factor for diabetes mellitus (DM), while triglycerides/high-density lipoprotein (TG/HDL) may be a risk factor for diabetes. However, no existing study has elucidated the interaction between TG/HDL and VD3. Therefore, this work aimed to investigate the relationships of TG/HDL with insulin resistance (IR), impaired glucose tolerance (IGT), and DM at different VD3 levels.. With the use of the data from five National Health and Nutrition Examination Survey (NHANES) cycles, a total of 2,929 males and 3,031 females were divided into 4 groups according to their VD3 levels. Logistic regression was performed to observe the associations of TG/HDL ratio with IR, IGT, and DM in different groups.. The relationships of TG/HDL with IR, IGT, and DM showed a threshold effect, with the cutoff values of 1.094, 1.51, and 1.11, respectively. On both sides of the cutoff values, the correlation was first weakened and then enhanced with the increase in VD3 levels.. TG/HDL is a risk factor for IR, IGT, and DM. Both too low and too high levels of VD3 can strengthen this association, whereas keeping VD3 at a reasonable level helps to reduce the associations of TG/HDL with IR, IGT, and DM.

Topics: Biomarkers; Cholecalciferol; Cholesterol, HDL; Diabetes Mellitus; Female; Glucose Intolerance; Humans; Insulin Resistance; Lipoproteins, HDL; Male; Nutrition Surveys; Triglycerides

The study aimed to investigate the potential nephroprotective effects of vitamin D3 in metabolic syndrome (MetS) and the molecular basis of the underlying mechanisms of its action.. MetS was induced in adult male Wistar rat‏s by adding fructose (10%) to every day drinking water and salt (3%) to the diet. Six weeks after fructose/salt consumption, fasting serum lipid profile and uric acid levels were determined, an oral glucose tolerance test (OGTT) was performed and kidney function was checked. MetS rats were then treated orally with vitamin D3 (10 µg/kg/day) for 6 weeks. At the end of the study period (12 weeks), the OGTT test was reperformed, anthropometrical parameters were measured, urine, blood and tissue samples were collected and the animals were euthanised.. The incidence of MetS was confirmed 6 weeks after fructose/salt consumption, when the rats exhibited significant weight gain, dyslipidemia, hyperuricemia, insulin resistance, hyperinsulinemia and impaired glucose tolerance. After 12 weeks, MetS rats displayed markedly declined renal function alongside with extravagant renal histopathological damages and interstitial fibrosis. Furthermore, significantly enhanced renal oxidative stress and inflammation were manifested. Vitamin D3 supplementation in MetS rats significantly reversed all the above-mentioned deleterious effects.. The study has indeed provided mounting evidence of the promising therapeutic potential of vitamin D3 against development and progression of MetS-induced nephropathy. A new insight has been introduced into the crucial role of dipeptidyl peptidase-4 inhibition and sirtuin-1/5'adenosine monophosphate-activated protein kinase activation in the renoprotective effects of vitamin D3.

Topics: Animals; Blood Glucose; Cholecalciferol; Dietary Supplements; Fructose; Insulin Resistance; Male; Metabolic Syndrome; Rats; Rats, Wistar

Equivocal association the contribution of 25-hydroxyvitamin D (25(OH)D) and the well-accepted role of vitamin D-binding protein (VDBP) on bioavailability of 25(OH)D or its independent roles, has led to possible association of the VDBP in glucose metabolism. This study was conducted to evaluate the relationships among 25(OH)D, VDBP, glucose/insulin metabolism and homeostatic model assessment (HOMA-IR). Blood samples were collected from 236 obese and overweight women. VDBP and 25(OH)D levels, and biochemical parameters were measured using an enzyme-linked immunosorbent assay (ELISA). An impedance fat analyzer was utilized to acquire the body composition.. Using the multivariate linear regression, a reverse relationship was observed between VDBP and (HOMA-IR), such that women with higher VDBP displayed lower insulin resistance. The relationship was independent of age, body mass index, standardized energy intake and physical activity (p = 0.00). No significant relationship between 25(OH)D levels, FBS, body composition or insulin resistance were observed (p > 0.2). Current study observed that higher level of VDBP may be associated with lower levels of insulin and HOMA-IR, thus the evaluation of VDBP in diverse population groups seems to have significant clinical value in evaluating the prevalence of DM or early stage of glucose intolerance.

Topics: Body Mass Index; Cholecalciferol; Female; Humans; Insulin; Insulin Resistance; Obesity; Overweight; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein

Topics: Calcitriol; Cholecalciferol; Dietary Supplements; Humans; Insulin Resistance; Non-alcoholic Fatty Liver Disease; Vitamin D

Topics: AMP-Activated Protein Kinases; Animals; Blood Glucose; Cholecalciferol; Creatinine; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Hyperuricemia; Hypoglycemic Agents; Insulin Resistance; Kidney; Kidney Cortex; Male; Malondialdehyde; MAP Kinase Signaling System; NADP; Oxidative Stress; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Sirtuin 1; Sodium Chloride; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha; Urea; Uric Acid; Vildagliptin

Vitamin D3 (vit. D3) deficiency is considered as one of the main factors involved in the development of type 2 diabetes (T2D). We assessed insulin resistance (IR), β-cell functional activity and metabolic profile according to 25(OH) vit. D3 status in patients with T2D.. The study included 109 patients with T2D, divided in 3 groups: group 1 (N.=11) with normal levels of vit. D3 (>30 ng/mL); group 2 (N.=38) with vit. D3 insufficiency (21-29 ng/mL); and group 3 (N.=60) with vit. D3 deficiency (<20 ng/mL). IR and β-cell functional activity were assessed as change in C-peptide concentration and homeostasis model assessment-estimated (HOMA) β-cell function which was calculated using HOMA2 calculator.. Patients with vit. D3 deficiency presented significantly higher C-peptide concentration compared to other groups. HOMA2 (3.29±1.89 vs. 2.12±0.71; P=0.049) and hemoglobin (H8b)A1c (9.11±1.63 vs. 7.75±1.06; P=0.016) levels changed significantly only in patients with vit. D3 deficiency compared to diabetics with normal vit. D3 levels. Furthermore, in univariate Pearson's correlation analysis, we observed significant association between vit. D3 levels and C-peptide, insulin sensitivity, HOMA2, triglyceride-glucose index, HbA1c and Body Mass Index, only in the vit. D3 deficiency group. In multivariate logistic regression analysis, poor glycemic control, as defined by HbA1c levels, was independent from metformin use while high density lipoprotein-cholesterol levels were associated with vit. D3 deficiency.. Our study demonstrated that vit. D3 deficiency in patients with T2D was associated with more severe IR, poor glycemic control and obesity compared to normal status or vit. D3 insufficiency.

Topics: Adolescent; Adult; Aged; Body Mass Index; C-Peptide; Cholecalciferol; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Ergocalciferols; Female; Glycemic Control; Humans; Hypoglycemic Agents; Insulin Resistance; Male; Metformin; Middle Aged; Obesity; Vitamin D Deficiency; Young Adult

Topics: Animals; Calcitriol; Cholecalciferol; Disease Models, Animal; Insulin Resistance; Mice; Obesity; Vascular Calcification; Vascular Remodeling; Vitamin D

The aim of this study was to identify the effects of vitamin D supplementation on insulin sensitivity and androgen levels in vitamin-D-deficient polycystic ovary syndrome (PCOS) patients.. Sixty-seven vitamin-D-deficient (25-hydroxyvitamin D [25(OH)D] levels below 20 ng/mL) PCOS patients and 54 vitamin-D-deficient non-PCOS volunteer subjects matched for age and body mass index were enrolled to this prospective study. All participants were given 50 000 IU/week cholecalciferol orally for 8 weeks and 1500 IU/day for 4 weeks. Insulin sensitivity was calculated with the Matsuda insulin sensitivity index (ISI) based on an oral glucose tolerance test. Matsuda ISI, gonadal hormones (estrogen, testosterone, androstenedione), and 25(OH)D levels were studied before and at the end of the 12th week of vitamin D load.. After vitamin D supplementation, serum androstenedione levels had decreased significantly (P = 0.007) and Matsuda ISI values had increased significantly (P = 0.001) in the PCOS group but no significant changes were seen in those parameters in controls. We observed positive correlations between 25(OH)D levels and Matsuda ISI (r = 0.307; P < 0.01), and negative correlations between 25(OH)D levels and total testosterone (r = -0.306; P < 0.01) and androstenedione (r = -0.275; P < 0.01) levels in the PCOS group.. Vitamin D supplementation increased insulin sensitivity and decreased androgen levels in vitamin-D-deficient women with PCOS but did not have any effect in vitamin-D-deficient non-PCOS women. These results may indicate the possible role of vitamin D in the complex pathogenesis of PCOS.

Topics: Adolescent; Adult; Androstenedione; Blood Glucose; Body Mass Index; Cholecalciferol; Dietary Supplements; Female; Humans; Insulin Resistance; Polycystic Ovary Syndrome; Prospective Studies; Testosterone; Vitamin D; Vitamin D Deficiency; Young Adult

Insulin resistance (IR) is accompanied by increased areal or volumetric bone mineral density (aBMD or vBMD), but also higher fracture risk. Meanwhile, imbalances in bone health biomarkers affect insulin production. This study investigates the effect of IR on proximal femur and lumbar spine BMD, femoral neck bending, compressive and impact strength indices (Composite Strength Indices) and circulating levels of parathyroid hormone (PTH), C-telopeptide of Type I collagen (CTx-1) and 25(OH) Vitamin D₃, in a cohort of 97 healthy, non-obese, menopausal Chinese-Singaporean women. Lumbar spine aBMD was inversely associated with IR and dependent on lean body mass (LBM) and age. No such associations were found for vBMD of the third lumbar vertebra, aBMD and vBMD of the proximal femur, or circulating levels of PTH, CTx-1 and 25(OH) Vitamin D₃. Composite Strength Indices were inversely associated with IR and independent of LBM, but after adjusting for fat mass and age, this association remained valid only for the impact strength index. Composite Strength Indices were significantly lower in participants with a high degree of IR. Our findings on IR and Composite Strength Indices relationships were in agreement with previous studies on different cohorts, but those on IR and BMD associations were not.

Topics: Aged; Bone Density; Bone Remodeling; Cholecalciferol; Collagen Type I; Female; Femur; Humans; Insulin Resistance; Lumbar Vertebrae; Menopause; Middle Aged; Parathyroid Hormone; Peptides

Prospective epidemiological studies have consistently shown a relationship between vitamin D deficiency, insulin resistance, and type 2 diabetes mellitus (DM2). This is supported by recent trials showing that vitamin D supplementation in prediabetic or insulin-resistant patients with inadequate vitamin D levels improves insulin sensitivity. However, the molecular mechanisms underlying vitamin D deficiency-induced insulin resistance and DM2 remain unknown. Skeletal muscle insulin resistance is a primary defect in the majority of patients with DM2. Although sustained activation of forkhead box O1 (FOXO1) in skeletal muscle causes insulin resistance, a relationship between vitamin D deficiency and FOXO1 activation in muscle is unknown. We generated skeletal muscle-specific vitamin D receptor (VDR)-null mice and discovered that these mice developed insulin resistance and glucose intolerance accompanied by increased expression and activity of FOXO1. We also found sustained FOXO1 activation in the skeletal muscle of global VDR-null mice. Treatment of C2C12 muscle cells with 1,25-dihydroxyvitamin D (VD3) reduced FOXO1 expression, nuclear translocation, and activity. The VD3-dependent suppression of FOXO1 activation disappeared by knockdown of VDR, indicating that it is VDR-dependent. Taken together, these results suggest that FOXO1 is a critical target mediating VDR-null signaling in skeletal muscle. The novel findings provide the conceptual support that persistent FOXO1 activation may be responsible for insulin resistance and impaired glucose metabolism in vitamin D signaling-deficient mice, as well as evidence for the utility of vitamin D supplementation for intervention in DM2.

Topics: Animals; Cell Line; Cell Nucleus; Cholecalciferol; Female; Forkhead Box Protein O1; Gene Deletion; Gene Expression Regulation; Glucose; Insulin Resistance; JNK Mitogen-Activated Protein Kinases; Male; Mice; Muscle Fibers, Skeletal; Muscle, Skeletal; Organ Specificity; Protein Transport; Receptors, Calcitriol; Vitamin D Deficiency

Vitamin D supplementation trials with diabetes-related outcomes have been conducted almost exclusively in adults and provide equivocal findings.. The objective of this study was to determine the dose-response of vitamin D supplementation on fasting glucose, insulin, and a surrogate measure of insulin resistance in white and black children aged 9–13 years, who participated in the Georgia, Purdue, and Indiana University (or GAPI) trial: a 12-week multisite, randomized, triple-masked, dose-response, placebo-controlled vitamin D trial.. Black and white children in the early stages of puberty (N = 323, 50% male, 51% black) were equally randomized to receive vitamin D3 (0, 400, 1000, 2000, or 4000 IU/day) for 12 weeks. Fasting serum 25-hydroxyvitamin D (25(OH)D), glucose and insulin were assessed at baseline and weeks 6 and 12. Homeostasis model assessment of insulin resistance was used as a surrogate measure of insulin resistance. Statistical analyses were conducted as intent-to-treat using a mixed effects model.. Baseline serum 25(OH)D was inversely associated with insulin (r = −0.140, P = 0.017) and homeostasis model assessment of insulin resistance (r = −0.146, P = 0.012) after adjusting for race, sex, age, pubertal maturation, fat mass, and body mass index. Glucose, insulin, and insulin resistance increased (F > 5.79, P < .003) over the 12 weeks, despite vitamin D dose-dependent increases in serum 25(OH)D.. Despite significant baseline inverse relationships between serum 25(OH)D and measures of insulin resistance, vitamin D supplementation had no impact on fasting glucose, insulin, or a surrogate measure of insulin resistance over 12 weeks in apparently healthy children.

Topics: Adolescent; Black People; Blood Glucose; Body Composition; Child; Cholecalciferol; Dietary Supplements; Dose-Response Relationship, Drug; Fasting; Female; Humans; Insulin; Insulin Resistance; Male; Vitamin D; White People

Atypical antipsychotics are associated with an increased risk of hyperglycaemia, thus limiting their clinical use. This study focused on finding the molecular mechanism underlying antipsychotic-induced hyperglycaemia. First, we searched for drug combinations in the FDA Adverse Event Reporting System (FAERS) database wherein a coexisting drug reduced the hyperglycaemia risk of atypical antipsychotics, and found that a combination with vitamin D analogues significantly decreased the occurrence of quetiapine-induced adverse events relating diabetes mellitus in FAERS. Experimental validation using mice revealed that quetiapine acutely caused insulin resistance, which was mitigated by dietary supplementation with cholecalciferol. Further database analysis of the relevant signalling pathway and gene expression predicted quetiapine-induced downregulation of Pik3r1, a critical gene acting downstream of insulin receptor. Focusing on the phosphatidylinositol 3-kinase (PI3K) signalling pathway, we found that the reduced expression of Pik3r1 mRNA was reversed by cholecalciferol supplementation in skeletal muscle, and that insulin-stimulated glucose uptake into C2C12 myotube was inhibited in the presence of quetiapine, which was reversed by concomitant calcitriol in a PI3K-dependent manner. Taken together, these results suggest that vitamin D coadministration prevents antipsychotic-induced hyperglycaemia and insulin resistance by upregulation of PI3K function.

Topics: Animals; Antipsychotic Agents; Cell Line; Cholecalciferol; Class Ia Phosphatidylinositol 3-Kinase; Data Mining; Databases, Factual; Disease Models, Animal; Glucose Transporter Type 4; Humans; Hyperglycemia; Insulin Resistance; Mice; Quetiapine Fumarate; Signal Transduction; Vitamin D

Topics: Cholecalciferol; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Male; Vascular Stiffness

Both insulin resistance (IR) and vitamin D deficiency (VDD) are found to be associated with many cancer types. In this study, we evaluated the presence of IR and VDD in thyroid cancer patients based on controls. Total 344 papillary thyroid cancer and 116 controls were part of the study. Glucose, insulin, homeostasis model analysis-insulin resistance (HOMA-IR) (control group 2.12 ± 0.9 and patient group 3.6 ± 1.1; p < 0.0001), LDL were significantly high; HOMA-S and vitamin D3 levels (control group 19.11 ± 8 and patient group 17 ± 16; p = 0.004) were significantly low in the patient group. Vitamin D deficiency (64/108 in controls vs 166/235; p = 0.026) and insulin resistance (24/108; 115/235; p < 0.0001) were more frequent in papillary thyroid cancer patients. After regression analysis, tumor diameter showed significant association with log-HOMA-IR (B = 0.315; p = 0.017) and log-vitamin D3 (B = 0.207; p = 0.04). Vitamin D deficiency and insulin resistance frequencies show no difference between micro- and macropapillary thyroid cancers. Receiver operating characteristic curve shows the best cutoff point for tumor diameter showing that the presence of lymph node metastasis was 0.65 cm with 81.2 % sensitivity and 52 % specificity. Best cutoff point for the capsular invasion tumor diameter was 0.75 cm with 83.3 % sensitivity and 60.4 % specificity. No difference between follicular and classical type papillary thyroid carcinomas has been yet discovered. As a result, thyroid cancer patients are more insulin resistant and vitamin D3 deficient. Vitamin D3 levels and HOMA-IR index may affect tumor diameter. Tumor size that is lower than 1 cm (0.65-0.75 cm) may be related with capsular invasion and lymph node involvement.

Topics: Adult; Carcinoma; Carcinoma, Papillary; Case-Control Studies; Cholecalciferol; Female; Folic Acid; Homeostasis; Humans; Insulin Resistance; Male; Middle Aged; ROC Curve; Thyroglobulin; Thyroid Cancer, Papillary; Thyroid Neoplasms; Vitamin B 12

To compare the effects of combined and individual supplementation of cholecalciferol and levo carnitine on plasma glucose, plasma insulin and insulin resistance in type 2 diabetic rats.. The randomised controlled trial was conducted at the Department of Physiology, Army Medical College, Rawalpindi, between October 2010 and April 2011. It comprised 80 healthy Sprague Dawley rats who were divided into four groups (n = 20 each). Rats were fed high-fat diet for 2 weeks followed by an intraperitoneal injection of streptozocin to induce type 2 diabetes mellitus. group I served as diabetic control; group II was given cholecalciferol; group III; levo carnitine; and group IV was administered cholecalciferol and levo carnitine together. After 6 days of supplementation, terminal intracardiac blood extraction was done and samples were analysed for fasting plasma glucose and plasma insulin. Insulin resistance was calculated by homeostatic model assessment for insulin resistance. SPSS 17.0 was used for statistical analysis.. Fasting plasma glucose levels were significantly decreased (p < 0.001) in the combined supplementation group compared to the diabetic control and individual supplementation groups. Combined supplementation showed a significant increase in fasting plasma insulin levels when compared with diabetic control and levo carnitine groups (p < 0.001), and the effect of combined supplementation on ameliorating insulin resistance was significantly better (p < 0.001) as compared to the individual supplementation of cholecalciferol and levo carnitine.. The combined supplementation of cholecalciferol and levo carnitine for 6 days markedly improved the glycaemic control, insulin secretion and insulin resistance in type 2 diabetic rats on high-fat diet A prolonged supplementation by both the compounds along with caloric restriction may yield a more promising outcome.

Topics: Analysis of Variance; Animals; Blood Glucose; Carnitine; Cholecalciferol; Diabetes Mellitus, Experimental; Insulin; Insulin Resistance; Random Allocation; Rats; Rats, Sprague-Dawley

We studied patients with a combination of diabetes and thyroid disorders, was assessed the provision of vitamin D3, markers of insulin resistance, impaired glucose and mineral metabolism. Studies indicate that patients with a marked deficiency of vitamin D3, and decompensation of carbohydrate obmela disturbance of mineral metabolism.

Topics: Adult; Biomarkers; Blood Glucose; Calcium; Cholecalciferol; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Pancreas; Parathyroid Hormone; Regression Analysis; Thyroid Gland; Thyroiditis, Autoimmune; Trace Elements; Vitamin D Deficiency

Associations between 25 hydroxy vitamin D [25(OH)D], adipokines levels, and insulin resistance have been reported. The aim of this study was to explore the effects of cholecalciferol supplementation on vitamin D levels, insulin resistance, leptin, and adiponectin levels in vitamin D-deficient peritoneal dialysis (PD) patients.. In nineteen vitamin D-deficient PD patients, who were treated with cholecalciferol, fasting serum glucose, insulin, adiponectin, leptin, 25(OH)D and parathyroid hormone (PTH) were measured before and after cholecalciferol replacement therapy. Eighteen (94.7 %) PD patients with vitamin D deficiency were receiving active vitamin D compounds (alphacalciferol) for PTH control. Alphacalciferol dosing was kept constant during treatment with cholecalciferol.. While mean 25(OH)D significantly increased from (10.2 ± 4.9 ng/ml) to (82.9 ± 56.5 ng/ml) (p < 0.05), mean homeostatic model assessment-insulin resistance index significantly decreased from (4.6 ± 3.6) to (2.8 ± 2.0) after cholecalciferol replacement therapy (p < 0.05). Serum leptin levels (12.9 ± 17.6 ng/ml) significantly increased (18.1 ± 19.5 ng/ml) (p < 0.05), while there was no change in serum adiponectin, calcium, and phosphate after vitamin D replacement. Serum PTH levels significantly decreased from 551.9 ± 276.6 pg/ml to 434.0 ± 273.4 ng/ml.. Cholecalciferol replacement therapy significantly decreases PTH levels and insulin resistance. The results of this study need to be confirmed in larger clinical trials.

Topics: Adipokines; Cholecalciferol; Female; Follow-Up Studies; Humans; Insulin Resistance; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peritoneal Dialysis; Pilot Projects; Prospective Studies; Vitamin D; Vitamin D Deficiency; Vitamins

To investigate the vascular dysfunction caused by insulin resistance in polycystic ovary syndrome (PCOS) and the effectiveness of vitamin D in an animal model.. Controlled experimental animal study.. Animal laboratory at a university research institute.. Thirty female Wistar rats.. Rats were divided into groups at age 21-28 weeks. Twenty of them were subjected to dihydrotestosterone (DHT) treatment (83 μg/d); ten of them also received parallel vitamin D treatment (120 ng/100 g/wk). Oral glucose tolerance tests with insulin level measurements were performed. Gracilis arterioles were tested for their contractility as well as their nitric oxide (NO)-dependent and insulin-induced dilation using pressure arteriography.. Several physiologic parameters, glucose metabolism, and pressure arteriography.. DHT treatment increased the passive diameter of resistance arterioles, lowered norepinephrine-induced contraction (30.1 ± 4.7% vs. 8.7 ± 3.6%) and reduced acetylcholine-induced (122.0 ± 2.9% vs. 48.0 ± 1.4%) and insulin-induced (at 30 mU/mL: 21.7 ± 5.3 vs. 9.8 ± 5.6%) dilation. Vitamin D treatment restored insulin relaxation and norepinephrine-induced contractility; in contrast, it failed to alter NO-dependent relaxation.. In DHT-treated rats, in addition to metabolically proven insulin resistance, decreased insulin-induced vasorelaxation was observed and was improved by vitamin D treatment without affecting NO-dependent relaxation. The reduction in insulin-induced dilation of arterioles is an important as yet undescribed pathway of vascular damage in PCOS and might explain the clinical effectiveness of vitamin D treatment.

Topics: Acetylcholine; Animals; Arterioles; Blood Glucose; Cholecalciferol; Dihydrotestosterone; Disease Models, Animal; Enzyme Inhibitors; Female; Glucose Tolerance Test; Insulin; Insulin Resistance; Muscle, Skeletal; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Polycystic Ovary Syndrome; Rats; Rats, Wistar; Vasodilation; Vasodilator Agents

Recent studies indicate that pravastatin improves whereas other statins impair glucose homeostasis in humans, but the underlying mechanisms are not clear. We examined the effect of pravastatin and atorvastatin on insulin sensitivity in a rat model.. Pravastatin (40 mg/kg/day) or atorvastatin (20mg/kg/day) were administered for 3 weeks and insulin sensitivity was assessed by measuring fasting plasma insulin, HOMA-IR, non-esterified fatty acids (NEFA) and glycerol levels, as well as by the hyperinsulinemic euglycemic clamp.. Pravastatin had no effect on fasting insulin and HOMA-IR but significantly reduced plasma NEFA and glycerol levels and increased glucose infusion rate (GIR) during the hyperinsulinemic clamp. Increase in GIR induced by pravastatin was not abolished by NO synthase inhibitor, l-NAME, indicating that this effect did not result from the improvement of endothelial function. Atorvastatin increased fasting insulin, HOM-IR, NEFA and glycerol levels as well as reduced GIR. Statins had no effect on leptin, HMW adiponectin, resistin, visfatin, interleukin-6 and TNF-α. Pravastatin increased plasma concentrations of 25-hydroxy- and 1,25-dyhydroxyvitamin D(3) (25-OH-D(3) and 1,25-(OH)(2)-D(3)), and its effect on insulin sensitivity was mimicked by exogenous 1,25-(OH)(2)-D(3). Atorvastatin reduced plasma 25-OH-D(3) but had no effect on 1,25-(OH)(2)-D(3). Decrease in insulin sensitivity induced by atorvastatin was not corrected by supplementation of vitamin D(3) despite normalization of plasma 25-OH-D(3) level.. Pravastatin and atorvastatin have opposite effects on insulin sensitivity and vitamin D(3) status. Pravastatin-induced increase in insulin sensitivity is mediated by elevation of 1,25-(OH)(2)-D(3). In contrast, atorvastatin-induced decrease in insulin sensitivity is independent of lowering 25-OH-D(3).

Topics: Adipokines; Adipose Tissue; Animals; Atorvastatin; Biomarkers; Blood Glucose; Calcifediol; Calcitriol; Cholecalciferol; Fasting; Fatty Acids, Nonesterified; Glucose Clamp Technique; Glycerol; Heptanoic Acids; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation Mediators; Insulin; Insulin Resistance; Liver; Male; Muscle, Skeletal; Pravastatin; Pyrroles; Rats; Rats, Wistar; Time Factors

Topics: Blood Glucose; Cholecalciferol; Fasting; Female; Humans; Insulin Resistance; Male; Prediabetic State

Vitamin D has in vitro and in vivo effects on β cells and insulin sensitivity. Vitamin D deficiency (VDD) has been associated with the onset and progression of type 2 diabetes mellitus (DM-2). However, studies involving supplementation of vitamin D in subjects with previously established diabetes have demonstrated inconsistent effects on insulin sensitivity. The aim of this open-label study was to assess the effects of high-dose vitamin D3 supplementation on insulin sensitivity in subjects with VDD and impaired fasting glucose. We studied 8 subjects with VDD and prediabetes with the modified, frequently sampled intravenous glucose tolerance (mFSIGT) test before and after vitamin D supplementation. Vitamin D3 was administered as 10,000 IU daily for 4 weeks. The mFSIGT was analyzed with MinMod Millennium (purchased from Dr. Richard Bergman, Keck School of Medicine of USC, Los Angeles, Calif) to obtain estimates of acute insulin response to glucose (AIRg), insulin sensitivity (SI), and disposition index (DI). We found that AIRg decreased (P = 0.011) and SI increased (P = 0.012) after a intervention with vitamin D. If these findings are repeated in a randomized, double-blind study, the results indicate that orally administered high-dose vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose and suggests that high-dose vitamin D3 supplementation might provide an inexpensive public health measure in preventing, or at least delaying, the progression from impaired fasting glucose to diabetes.

Topics: Adult; Blood Glucose; Calcium; Cholecalciferol; Dietary Supplements; Fasting; Female; Humans; Insulin Resistance; Male; Middle Aged; Parathyroid Hormone; Prediabetic State; Prospective Studies; Vitamin D; Vitamin D Deficiency

The skeletal protein osteocalcin is gamma-carboxylated by vitamin K. High serum uncarboxylated osteocalcin reflects low vitamin K status. In vitro and animal studies indicate that high uncarboxylated osteocalcin is associated with reduced insulin resistance. However, associations between osteocalcin and measures of insulin resistance in humans are less clear.. Our aim was to examine cross-sectional and longitudinal associations between circulating forms of osteocalcin (total, uncarboxylated, and carboxylated) and insulin resistance in older men and women.. Cross-sectional associations between serum measures of total osteocalcin, carboxylated osteocalcin, and uncarboxylated osteocalcin and insulin resistance were examined in 348 nondiabetic men and women (mean age: 68 y; 58% female) by using the homeostasis model assessment of insulin resistance (HOMA-IR). Associations between each form of osteocalcin at baseline and 3-y change in HOMA-IR were examined in 162 adults (mean age: 69 y; 63% female) who did not receive vitamin K supplementation.. Lower circulating uncarboxylated osteocalcin was not associated with higher HOMA-IR at baseline or at 3-y follow-up. Those in the lowest tertiles of total osteocalcin and carboxylated osteocalcin at baseline had higher baseline HOMA-IR (P = 0.006 and P = 0.02, respectively). The concentration of carboxylated osteocalcin at baseline was inversely associated with a 3-y change in HOMA-IR (P = 0.002).. In older adults, circulating uncarboxylated osteocalcin was not associated with insulin resistance. In contrast, elevated carboxylated osteocalcin and total osteocalcin were associated with lower insulin resistance, which supports a potential link between skeletal physiology and insulin resistance in humans. The role of vitamin K status in this association remains unclear and merits further investigation. This trial is registered at clinicaltrials.gov as NCT00183001.

Topics: Adiponectin; Aged; Blood Glucose; Body Mass Index; Calcium; Cholecalciferol; Cross-Sectional Studies; Exercise; Female; Homeostasis; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Models, Biological; Osteocalcin; Vitamin K 1; Vitamins

The aim of this study was to explore the effects of cholecalciferol supplementation on vitamin D levels, bone mineral density (BMD), body fat distribution and insulin sensitivity in vitamin D-deficient HIV-1-infected patients.. Twenty vitamin D-deficient HIV-1-infected patients were prospectively treated with 2000 IU cholecalciferol/day for 14 weeks, whereafter treatment was continued with half this dosage until 48 weeks. BMD, body fat distribution, 1,25-dihydroxy vitamin D(3) (1,25(OH)2D3), fasting glucose, insulin, adiponectin, leptin, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha were measured at baseline, and at 24 and 48 weeks. Parathyroid hormone (PTH), 25-hydroxy vitamin D(3) [25(OH)D(3)], cholesterol and triglycerides were measured at baseline, and at 12, 24 and 48 weeks.. After 24 weeks, cholecalciferol supplementation significantly increased 25(OH)D3 and 1,25(OH)2D3 levels and decreased PTH and insulin sensitivity. After 48 weeks, however, only 25(OH)D3 levels remained significantly different from baseline, while the other parameter levels returned to baseline, suggesting a dose-response effect. Cholecalciferol had no effect on BMD, adipokines and triglycerides.. The effect of cholecalciferol treatment in this cohort appears to be dose dependent. Cholecalciferol dosages of > or =2000 IU are necessary to achieve 1,25(OH)2D3 levels that significantly decrease PTH, but also negatively affect insulin sensitivity. The results of this hypothesis-driven explorative study need to be confirmed in larger clinical trials.

Topics: Body Fat Distribution; Bone Density; Bone Density Conservation Agents; Cholecalciferol; Dietary Supplements; Female; HIV Infections; HIV-1; Humans; Insulin Resistance; Male; Middle Aged; Pilot Projects; Prospective Studies; Vitamin D Deficiency

The aim of this study was to evaluate the effect of vitamin D3 supplementation on insulin secretion and insulin resistance. Ten females with type 2 diabetes being treated with oral hypoglycaemic agents and with normal serum and urine calcium levels were enrolled in the study. The study was conducted in March, when levels of vitamin D are lowest in our region. The level of plasma 25(OH)D was measured (normal range in winter 25-120 nmol/l). The first (FPIS) and second (SPIS) phases of insulin secretion were studied during IVGTT. Peripheral insulin resistance was measured. A group of 17 age- and BMI-matched females with normal glucose tolerance served as a control group. The diabetic patients were treated with cholecalciferol 1332 IU daily for one month. The mean plasma 25(OH)D level was 35.3 +/- 15.1 nmol/l at baseline, 70% of patients being vitamin D deficient. After one month of treatment with vitamin D3, the plasma 25(OH)D level increased by a mean of 75.8%; 70% of the patients achieved normal vitamin D levels. FPIS increased significantly by 34.3%, while the change in SPIS of 20.4% was not significant (p > 0.8). We found a significant correlation between the change in FPIS and the change in 25(OH)D level after vitamin D3 supplementation (p < 0.018). The results showed a decrease of 21.4% in insulin resistance after one month, but the change was not significant. Bearing in mind that the main defects in type 2 diabetes mellitus are reduced FPIS and insulin resistance, and the favourable effect vitamin D3 had on them, we suggest vitamin D3 deficiency may at least partly contribute to the impairment of insulin secretion and probably of insulin action. Our results suggest that vitamin D3 supplementation could be an element in the complex treatment of type 2 diabetes mellitus during the winter.

Topics: Adult; Aged; Analysis of Variance; Blood Glucose; Calcifediol; Case-Control Studies; Cholecalciferol; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Middle Aged; Seasons; Vitamin D Deficiency