Influence of vitamin D status on insulin secretion and glucose tolerance in the rabbit

The influence of vitamin D status on insulin secretion and glucose tolerance was studied by a longitudinal design in the rabbit. Intravenous glucose tolerance tests were performed in Dutch rabbits (n = 12) before and after nutritional vitamin D deficiency, characterized by an absence of circulating 25-hydroxyvitamin D3, a 50% decrease in 1,25-dihydroxyvitamin D3, and a 16% decrease in serum calcium concentrations. Glucose-induced insulin secretion was reduced by 41% as early as 2 months after the start of the vitamin D-deficient diet and was associated with an impairment of glucose tolerance. An iv calcium infusion restored the serum calcium concentration of the vitamin D-deficient rabbits (n = 5), but did not improve glucose-mediated insulin secretion. When these animals received a single ip injection of 100 ng 1,25-dihydroxyvitamin D3 10 h before the glucose test, their insulin responses significantly increased. Supplementation with 25-hydroxyvitamin D3 for 2 weeks in another group of rabbits (n = 4) resulted in marked improvement in glucose-stimulated insulin release and glucose tolerance. These results show that vitamin D affects glucose-induced insulin secretion by a mechanism that involves more than its regulating action on serum calcium concentration.     

Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice

Aims/hypothesis 1,25-dihydroxyvitamin D₃, the active form of vitamin D, prevents Type 1 diabetes in non-obese diabetic (NOD) mice. Epidemiological data show a threefold increase in human Type 1 diabetes when vitamin D deficiency was present in the first months of life. To evaluate whether a similar dietary deficiency affects diabetes incidence in NOD mice, we generated NOD mice with vitamin D deficiency in early life.Methods Breeding pairs of NOD mice, as well as their offspring (test mice), were kept in surroundings devoid of ultraviolet light and were fed a vitamin D-depleted diet for 100 days. Mice were followed for 250 days.Results At 250 days, 35% (12/35) male and 66% (22/33) female vitamin D-deficient mice were diabetic compared to 15% (6/40, p=0.05) and 45% (13/29, p<0.01) of the control mice. At 100 days no difference in insulitis was seen, but more vitamin D-deficient mice were glucose intolerant. Higher IL1 expression was detected in islets of vitamin D-deficient mice and their peritoneal macrophages had an aberrant cytokine profile (low IL1 and IL6, high IL15). Thymus and lymph nodes of vitamin D-deficient mice contained less CD4⁺CD62L⁺ cells.Conclusion/interpretation Vitamin D status increases the expression of Type 1 diabetes in NOD mice. Our data in NOD mice, as well as human epidemiological data, point to the importance of preventing vitamin D deficiency in early childhood. Controlling this dietary factor could be an easy and safe way to reduce the incidence of Type 1 diabetes in subjects who are genetically at risk.Abbreviations 1,25(OH)₂D₃ 1,25-dihydroxyvitamin D₃ - 25(OH)D₃ 25-hydroxyvitamin D₃ - BW body weight - HBSS Hanks balanced salt solution - IP interferon-inducible protein - IPGTT intra-peritoneal glucose tolerance test - iNOS inducible nitric oxide synthase - LPS lipopolysaccharide - MCP monocyte chemo-attractant protein - MIP macrophage inflammatory protein - MLR mixed lymphocyte reaction - NOD non-obese diabetic - RPMI Roswell Park Memorial Institute - UV ultraviolet     

A randomized, placebo-controlled trial of vitamin D supplementation to improve glycaemia in overweight and obese African Americans

Aims: 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. Methods: 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. Results: 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. Conclusions: Supplementation with 4000 IU/day vitamin D₃ 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.     

Effects of vitamin D deficiency and repletion on insulin and glucagon secretion in man

Summary We have studied the effects of vitamin D deficiency on pancreatic A- and B-cell function. Four subjects with vitamin D deficiency and 10 healthy subjects were studied. Pancreatic B-cell function was assessed by the insulin response to an oral glucose tolerance test. An insulin tolerance test was used to evaluate pancreatic A-cell function. The patients were then treated with 2000 U/day of vitamin D₃ for 6 months, after which the clinical, metabolic, biochemical and radiological features of vitamin D deficiency resolved, and pancreatic A-and B-cell function was repeated. In the vitamin D-deficient subjects pre-treatment and post-treatment serum calcium levels (mean±SEM) were 2.22±0.01 mmol/l and 2.24±0.01 mmol/1 respectively, and 2.27 ± 0.02 mmol/l in healthy subjects (NS). The pre-treatment level of 1,25-dihydroxy vitamin D (1,25-(OH)₂D) of 29.7 ± 3.3 pg/ml in the vitamin D deficient subjects rose to 70.3±10.3pg/ml after treatment (p < 0.05). The 1,25-(OH)₂D level in the healthy subjects was 50.0 ± 13.7 pg/ml (p < 0.05 versus pre- and post-treatment values in the patients). Insulin secretion, calculated by the area under the insulin curve, was significantly lower before vitamin D₃ treatment in the patients (9.09±0.7 mU × min,p<0.05) compared with the healthy subjects (11.9±0.5 mU × min) and post-treatment values of the patients with vitamin D deficiency (13.7 ± 0.5 mU x min). Similar changes were seen in the insulogenic indicesΔ I/ΔG). WhileΔI/ΔG was 1.71±0.4 (mean ± SEM) during vitamin D deficiency, it increased to 2.48±0.3 with vitamin D repletion. The insulogenic index in the healthy subjects was 2.68±0.3. The glucose areas were not significantly different. Insulin-induced glucagon secretion was similar in all instances. The results of this study suggest that vitamin D deficiency reduces pancreatic insulin secretion but it does not affect pancreatic A-cell function.     

Treatment with One-alpha-hydroxycholecalciferol in Middle-aged Men with Impaired Glucose Tolerance—A Prospective Randomized Double-blind Study

ABSTRACT Experimental evidence suggests a specific role for the active metabolite of vitamin D (1,25(OH)₂D₃) in insulin secretion. In order to evaluate the possible clinical significance, 65 middle-aged men with impaired glucose tolerance, and normal serum levels of vitamin D metabolites, were enrolled in a three-month study where they were given either 0.75 μg alpha-calcidol (1α(OH)D₃) daily or placebo. Indices of glucose and lipid metabolism were evaluated before and after treatment. There were no significant changes during the trial neither for fasting blood glucose, hemoglobin A_1C or for the intravenous glucose tolerance between the treatment and the placebo groups, nor were there any consistent changes in insulin values during the glucose tolerance test. Subjects treated with alpha-calcidol displayed a significant reduction in body weight with an average of 1.1. kg, while those receiving placebo lost no weight. Treatment did not affect the serum lipoprotein values. Thus, a modest dose of active vitamin D, which did not cause elevation of serum calcium, did not provide general improvement of glucose tolerance or of insulin secretion when given to patients with impaired glucose tolerance, but without vitamin D deficiency, over a three-month period.     

Vitamin D deficiency in the aetiology of obesity‐related insulin resistance

The obese insulin‐resistant state is often associated with low circulating concentration of vitamin D 25‐hydroxyvitamin D₃ [25(OH)D₃]. Fat sequestration of vitamin D in the expanded obese adipose tissue mass has been pointed out as a plausible explanation for this circulating vitamin D deficiency. However, the putative mechanisms behind this hypovitaminosis D remain to be elucidated. The presence of vitamin D receptor and vitamin D–metabolizing enzymes in insulin‐sensitive organs suggests that vitamin D may be involved in glucose and lipid metabolism and may be related to insulin sensitivity. Indeed, mainly in vitro studies support a role of vitamin D in regulating glucose and lipid metabolism in several insulin‐sensitive tissues including adipose tissue, skeletal muscle, liver, as well as pancreatic insulin secretion. A potential role of vitamin D in gut barrier function and metabolism has also been suggested. This review summarizes recent knowledge on vitamin D deficiency in the aetiology of obesity‐related insulin resistance and discusses potential underlying mechanisms. Finally, the role of vitamin D supplementation on insulin sensitivity and glycaemic control is discussed.     

Vitamin D deficiency,osteomalacia, and primary biliary cirrhosis

Five patients with primary biliary cirrhosis and vitamin D deficiency (serum 25-hydroxyvitamin D less than 6 ng/ml) are presented. All patients had low serum 24, 25-dihydroxyvitamin D₃ concentrations. Three patients had histological osteomalacia, negative calcium balance, and subnormal serum 1,25-dihydroxyvitamin D₃. Malabsorption of a standard dose of [³H]vitamin D₃ was found in three of four patients with steatorrhea, enabling the effective dose of vitamin D₃ given to be calculated. Oral vitamin D₃ 400–4000 IU/day (effectively 400–1860 IU/day) resulted in a return to normal of the serum vitamin D metabolites, correction of the impaired intestinal calcium absorption and healing of the osteomalacia. Increases in serum calcium, phosphate, and the renal tubular reabsorption of phosphate occurred with a concomitant decrease in serum parathyroid hormone. It is suggested that osteomalacia in primary biliary cirrhosis is the end result of vitamin D deficiency; the hepatic and renal hydroxylations of vitamin D are normal and target tissues are responsive to endogenously produced metabolites of vitamin D.     

Osteomalacia and celiac disease: Response to 25-hydroxyvitamin D

In this 54 year old woman with celiac disease, osteomalacia developed while she was on a gluten-free diet which had caused regression of her steatorrhea. She was not responsive to large doses of parenterally administered dihydrotachysterol and calcium, but she was responsive to the oral administration of 25-hydroxyvitamin D₃ (25-OHD₃). The data suggest that 25-OHD₃ Is the treatment of choice for patients with vitamin D deficiency due to intestinal malabsorption.     

Cloning and expression of rat 25-hydroxyvitamin D3-1α-hydroxylase cDNA

A full-length cDNA for the rat kidney mitochondrial cytochrome P450 mixed function oxidase, 25-hydroxyvitamin D₃-1α-hydroxylase (P4501α), was cloned from a vitamin D-deficient rat kidney cDNA library and subcloned into the mammalian expression vector pcDNA 3.1(+). When P4501α cDNA was transfected into COS-7 transformed monkey kidney cells, they expressed 25-hydroxyvitamin D₃-1α-hydroxylase activity. The sequence analysis showed that P4501α was of 2,469 bp long and contained an ORF encoding 501 amino acids. The deduced amino acid sequence showed a 53% similarity and 44% identity to the vitamin D₃-25-hydroxylase (CYP27), whereas it has 42.6% similarity and 34% identity with the 25-hydroxyvitamin D₃-24-hydroxylase (CYP24). Thus, it composes a new subfamily of the CYP27 family. Further, it is more closely related to the CYP27 than to the CYP24. The expression of P4501α mRNA was greatly increased in the kidney of vitamin D-deficient rats. In rats with the enhanced renal production of 1α,25-dihydroxyvitamin D₃ (rats fed a low Ca diet), P4501α mRNA was greatly increased in the renal proximal convoluted tubules.     

Metabolic acidosis in the vitamin D-deficient chick

In vitamin D-deficient chicks raised from age 1 day on a vitamin D-deficient diet, hyperchloremic metabolic acidosis occurred at 3 wk and persisted. Within 24 hr of administration of vitamin D, the acidosis and hypocalcemia were attentuated; during the subsequent 72 hr the severity of the metabolic acidosis but not that of the hypocalcemia was further attenuated. That further attenuation occurred despite hypocalcemia of unchanging severity and presumed continuing secondary hyperparathyroidism suggests the possibility that vitamin D deficiency may be a requirement for the expression of metabolic acidosis. Since in vitro and in vivo studies suggest that subphysiologic values of media and blood pH, respectively, are attended by reduced production of 1,25-(OH)₂D₃, the most biologically active vitamin D metabolite known, the occurrence of acidosis in vitamin D deficiency may compound its metabolic consequences. The possible effects of acidosis must be considered in interpreting results of investigations of vitamin D metabolism in vitamin D-deficient chicks.     

Interpreting Vitamin D Assay Results: Proceed with Caution

Vitamin D deficiency and insufficiency are common in patients with CKD. Association studies suggest that low 25-hydroxyvitamin D₃ (25-OH-D₃) is a harbinger of poor outcomes in these patients. Serum 25-OH-D represents the best biomarker of vitamin D status, but there is much debate surrounding the performance of some of the assay methods. Programs such as the Vitamin D Standardization Program and Vitamin D External Quality Assessment Scheme (DEQAS) in the United Kingdom have allowed us to assess the accuracy and reproducibility of the available methods. Liquid chromatography–tandem mass spectrometry–based methods for serum 25-OH-D measurement are emerging as more accurate and reliable alternatives to the immunoassay-based methods that have dominated over the past 2 decades. There is a renewed optimism that serum 25-OH-D is a useful biomarker to be used in patients with CKD, in particular to diagnose vitamin D deficiency and monitor vitamin D therapy. This commentary discusses some of the methodologic problems associated with serum 25-OH-D assays and their resolution, and looks forward to the future of vitamin D testing.     

Vitamin D deficiency and anemia: a cross-sectional study

Vitamin D has been suggested to have an effect on erythropoiesis. We sought to evaluate the prevalence of anemia in a population of individuals with vitamin D deficiency compared with those with normal levels in a population of a large integrated healthplan. A cross-sectional analysis in the period 1 January 2004 through 31 December 2006 of subjects with documented concurrent levels of 25-hydroxyvitamin D and hemoglobin were evaluated. Vitamin D deficiency was defined as <30 ng/mL and anemia was defined as a hemoglobin <11 g/dL. A total of 554 subjects were included in the analysis. Anemia was present in 49% of 25-hydroxyvitamin D-deficient subjects compared with 36% with normal 25-hydroxyvitamin D levels (p < 0.01). Odds ratio for anemia in subjects with 25-hydroxyvitamin D deficiency using logistic regressions and controlling for age, gender, and chronic kidney disease was 1.9 (95% CI 1.3–2.7). 25-hydroxyvitamin D-deficient subjects had a lower mean Hb (11.0 vs. 11.7; p = 0.12 ) and a higher prevalence of erythrocyte stimulating agent use (47% vs. 24%; p < 0.05). This study demonstrates an association of vitamin D deficiency and a greater risk of anemia, lower mean hemoglobin, and higher usage of erythrocyte-stimulating agents. Future randomized studies are warranted to examine whether vitamin D directly affects erythropoiesis.     

Low patient compliance—A major negative factor in achieving vitamin D adequacy in elderly hip fracture patients supplemented with 800 IU of vitamin D3 daily

Achievement of adequate vitamin D₃ level is crucial for the treatment of hip fracture patients. Currently used vitamin D₃ supplementation in Israel ranges between 200 and 800 IU/day. The study objectives were to evaluate the effects of 800 IU/day vitamin D₃ and 1.200 mg of calcium carbonate supplementation to achieve adequate vitamin D₃ level of 30 ng/ml in elderly hip fracture patients. One hundred and twenty-two elderly patients after surgical hip fracture correction aged 73.0 ± 9.5, who were enrolled in a post-surgical treatment program (PSTP). The patients received 800 IU of vitamin D₃ and 1.200 mg of calcium carbonate daily. Serum 25(OH)D and plasma PTH levels were assessed during initial hospital stay and at quarterly follow-up visits for 2 years. At baseline, 120 patients (98.4%) had 25(OH)D serum level <30 ng/ml. Forty-two patients (34.4%) had 25(OH)D serum level <10 ng/ml and these were considered as vitamin D₃ deficient. After 3 months, 29 patients (23.8%) were fully adherent to the supplement, 32 were (26.2%) partially adherent. The dropout rate at 1 year was 55.7%. The major reason for the discontinuation of participation was non-compliance. We conclude that the majority of elderly hip fracture patients had inadequate 25(OH)D serum levels. Compliance with calcium and vitamin D₃ supplements was extremely low. An adequate vitamin D status was not achieved with daily vitamin D₃ supplementation of 800 IU. Supplementation strategies using a periodic single high dose of vitamin D₃ might be more appropriate and should be considered in these patients.     

Vitamin D Deficiency Is an Independent Risk Factor for Urinary Tract Infections After Renal Transplants

Vitamin D deficiency is frequently found in patients with renal transplants (RTxs). Because vitamin D plays indispensable roles in the immune system, there may be an association between vitamin D deficiency and infection in these patients, but this has not been fully elucidated. Therefore, this study investigated the impact of pre-RTx vitamin D deficiency on urinary tract infection (UTI) development after RTx.We measured 25-hydroxyvitamin D3 (25(OH)D3) levels in 410 patients 2 weeks before they underwent RTx. Vitamin D deficiency was defined as 25(OH)D3 <10 ng/mL. The primary outcome was UTI occurrence after RTx. Cox proportional hazard analysis determined whether vitamin D deficiency was independently associated with UTI.The mean 25(OH)D3 level was 12.8 ± 6.9 ng/mL, and 171 patients (41.7%) were vitamin D deficient. During a median follow-up duration of 7.3 years, the UTI incidence was significantly higher in vitamin D-deficient patients (52 patients, 30.4%) compared with vitamin D-nondeficient patients (40 patients, 16.7%) (P = 0.001). Moreover, multivariate Cox proportional hazard analysis showed that vitamin D deficiency was an independent predictor of UTI after RTx (hazard ratio 1.81, 95% confidence interval 1.11–2.97, P = 0.02).Vitamin D deficiency was an independent risk factor for UTI after RTx; hence, determining 25(OH)D3 levels might help to predict infectious complications after RTx.     

Correlation between vitamin D3 deficiency and insulin resistance in pregnancy

BACKGROUND: The serum level of 25-hydroxyvitamin D deficiency has long been suspected as a risk factor for glucose intolerance and perhaps 1,25-dihydroxyvitamin D has a role in the regulation of insulin secretion. This study investigates the relation between 25-hydroxyvitamin D concentrations and insulin resistance in pregnant women. METHODS: A cross-sectional study was conducted on 741 pregnant women referred to five educating hospital clinics. Universal screening was performed with a GCT-50 g, and those with plasma glucose levels > pr = 7.2 mmol/L were diagnosed as GDM if they had an impaired GTT-100 g based on Carpenter and Coustan criteria. The levels of insulin and C-peptide were measured during OGTT-100 g test. The homeostasis model assessment index (HOMA) equation was used as the insulin resistance index. The concentrations of 25-hydroxyvitamin D, and PTH were also measured. RESULTS: Total prevalence of vitamin D deficiency (<25 nmol/L) was found in 70.6% of pregnant women. Prevalence of severe vitamin D deficiency (<12.5) in GDM patients was higher than in normoglycaemic pregnancies. The regression model revealed a strong correlation between the HOMA index and serum levels of vitamin D. CONCLUSIONS: These results show that a positive correlation of 25(OH) vitamin D concentrations with insulin sensitivity and vitamin D deficiency could be a confirmative sign of insulin resistance.     

The effect of cholecalciferol supplementation on vitamin D levels and insulin sensitivity is dose related in vitamin D-deficient HIV-1-infected patients

Objective

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.

Methods

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 D₃ (1,25(OH)₂D₃), fasting glucose, insulin, adiponectin, leptin, interleukin (IL)‐6 and tumour necrosis factor (TNF)‐α were measured at baseline, and at 24 and 48 weeks. Parathyroid hormone (PTH), 25‐hydroxy vitamin D₃ [25(OH)D₃], cholesterol and triglycerides were measured at baseline, and at 12, 24 and 48 weeks.

Results

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.

Conclusions

The effect of cholecalciferol treatment in this cohort appears to be dose dependent. Cholecalciferol dosages of ≥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.     

The physiologic significance of plasma transport of vitamin D and metabolites

Vitamin D and its metabolites do not circulate free but are bound to specific plasma transport proteins that solubilize them and protect them from oxidative inactivation. A specific vitamin D transport protein has been demonstrated in man, rat and chick; it preferentially binds 25-hydroxyvitamin D (25-(OH)D), the major active form of the vitamin in the circulation. The binding of vitamin D and its analogs by the D/25-(OH)D transport protein from rat plasma involves recognition of structural properties and steric configuration of both the single ring and the side chain. The C-25 hydroxyl group plus the vitamin D₃ configuration of both the side chain and the single ring maximize the binding. Although the binding of vitamin D₂ and its analogs by human and rat D/25-(OH)D transport protein is roughly equivalent to that of vitamin D₃ and its analogs, abnormal plasma binding of vitamin D₂ and 25-(OH)D₂ by the D/25-(OH)D transport protein in chick plasma may play an important role in the increased metabolic inactivation of these compounds and the resultant decreased antirachitic potency of vitamin D₂ in the chick. Preliminary studies suggest that 1,25-(OH)₂D is carried by the D/25-(OH)D transport protein in rat plasma but that a specific dihydroxy transport protein also exists in human plasma. These studies suggest that transport proteins play an important role in the facilitation of vitamin D transport and normal vitamin D metabolism.     

No improvement in cardiovascular risk factors in overweight and obese subjects after supplementation with vitamin D3 for 1 year

Abstract. Jorde R, Sneve M, Torjesen P, Figenschau Y (University of Tromsø, Tromsø; Medical Clinic University Hospital of North Norway, Tromsø; University Hospital of North Norway, Tromsø; Aker University Hospital, Oslo; University Hospital of North Norway, Tromsø; and University of Tromsø, Tromsø; Norway). No improvement in cardiovascular risk factors in overweight and obese subjects after supplementation with vitamin D₃ for 1 year. J Intern Med 2010; 267 :462–472. Background and Aim. Cross‐sectional studies indicate vitamin D to be of importance for glucose tolerance, blood pressure and serum lipids, but whether supplementation with vitamin D would improve cardio‐vascular risk factors is not known. Design and Setting. The study was a 1 year, double blind placebo‐controlled intervention trial performed at the University Hospital of North Norway from November 2005 to October 2007. Subjects. A total of 438 overweight or obese subjects, 21–70 years old, were included and 330 completed the study. Interventions. The subjects were randomized to vitamin D (cholecalciferol, vitamin D₃) 40 000 IU per week (DD group), vitamin D 20 000 IU per week (DP group), or placebo (PP group). All subjects were given 500 mg calcium daily. Main Outcome Measures. Fasting serum lipids and blood pressure were measured and an oral glucose tolerance test performed at start and end of the study. Results. At baseline the mean serum 25(OH)D levels were 58 nmol L^?1 (all subjects) and increased to 140 and 101 nmol L^?1 in the DD and DP groups, respectively. No significant differences were found between the three groups regarding change in measures of glucose metabolism or serum lipids. In the DP group, there was a slight but significant increase in systolic blood pressure compared with the placebo group. Conclusions. Our results do not support a positive effect of vitamin D on glucose tolerance, blood pressure or serum lipids. Further studies in subjects with low serum 25(OH)D levels combined with impaired glucose tolerance, hypertension or dyslipidaemia are needed.     

Synthesis and determination of configuration of natural 25-hydroxyvitamin D(3) 26,23-lactone

The four stereoisomers of 25-hydroxyvitamin D₃ 26,23-lactone were synthesized by a stereoselective lactonization method. Natural 25-hydroxyvitamin D₃ 26,23-lactone was produced from 25-hydroxy-[3α-³H]vitamin D₃ by in vitro incubation of kidney homogenate prepared from vitamin D-supplemented chickens or was isolated from the serum of rats given 1,25-dihydroxyvitamin D₃ and 25-hydroxy-[3α-³H]vitamin D₃. The four synthetic isomers and the naturally produced 25-hydroxyvitamin D₃ 26,23-lactone were subjected to high-performance liquid chromatography in a system capable of separating the four isomers. The natural lactone comigrated with synthetic (23S,25R)-25-hydroxyvitamin D₃ 26,23-lactone, establishing it as the natural vitamin D₃ metabolite.     

Effect of vitamin D3 loading and thyroid hormone replacement therapy on the decreased serum 25-hydroxyvitamin D level in patients with hypothyroidism

Twelve hypothyroid subjects, 13 healthy and 12 healthy women with a slight deficiency of vitamin D were studied to distinguish seasonal changes from the thyroxine-dependent ones. Serum 25-hydroxyvitamin D levels of hypothyroid patients were lower than those of healthy individuals when the sera were obtained in the autumn. In hypothyroid patients a single oral dose of 100,000 IU vitamin D3 resulted in a smaller increase in 25-hydroxyvitamin D concentration than in controls having subclinical exogenous vitamin D deficiency. Substitution therapy with thyroid hormone, started in our study always in autumn, increased the 25-hydroxyvitamin D concentration in hypothyroid patients, which was opposite to the autumn-to-spring variation of this hormone observed in healthy controls. The increase of 25-hydroxyvitamin D, dehydroepiandrosterone and its sulphate values following substitution therapy in the hypothyroid patients may indicate that thyroid hormone(s) is (are) involved in the regulation of steroid hormone synthesis.