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Type-2 diabetes is a nationally growing health concern. Previous literature has implicated that vitamin D deficiency and type-2 diabetes are interconnected. At this time there are no guidelines in place to guide the evaluation or treatment of vitamin D deficiency in type-2 diabetic patients. In order to create up to date guidelines for the treatment and evaluation of vitamin D deficiency in type-2 diabetic patients an integrative literature review was conducted using EMBASE, PubMed, and CINAHL. The literature review resulted in 44 articles that met the inclusion and exclusion criteria. The literature review resulted in the creation of five clinical recommendations. The most significant change to current clinical standards includes screening all type-2 diabetic patients for vitamin D deficiency. Vitamin D supplementation is not recommended for use in treating type-2 diabetes, diabetic complications, or preventing the progression from prediabetes to diabetes. However, type-2 diabetic patients with vitamin D deficiency should be treated with vitamin D supplementation to improve indirect health outcomes and prevent morbidity and mortality.

by Priscilla Miu-kuen Poon. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1991. / Includes bibliographical references. / ACKNOWLEDGEMENT --- p.1 / ABSTRACT --- p.2 / CONTENTS / Chapter 1. --- INTRODUCTION --- p.4 / Chapter 1.1 --- Discovery of vitamin D / Chapter 1.2 --- Bioavailability of vitamin D and its metabolites / Chapter 1.3 --- Metabolism of vitamin D and its metabolites / Chapter 1.4 --- Mode of action of vitamin D / Chapter 1.5 --- Vitamin D-related diseases / Chapter 2. --- METHODS OF MEASURING VITAMIN D AND ITS METABOLITES --- p.32 / Chapter 2.1 --- Deproteinization / Chapter 2.2 --- Extraction / Chapter 2.3 --- Separation / Chapter 2.4 --- Quantitation / Chapter 3. --- OBJECTIVES --- p.51 / Chapter 4. --- MATERIALS & METHODS --- p.52 / Chapter 4.1 --- Materials / Chapter 4.2 --- General methods / Chapter 4.3 --- Blood collection / Chapter 4.4 --- Radioreceptor assay / Chapter 4.5 --- Serum treatment / Chapter 4.6 --- High Performance Liquid Chromatography (HPLC) / Chapter 4.7 --- Gas Chromatography-Mass Spectrometry (GC-MS) / Chapter 4.8 --- "Serum 1α,25-dihydroxyvitamin D3 analysis" / Chapter 4.9 --- Application of the established GC-MS method / Chapter 4.10 --- Study on hypercalcaemia of tuberculosis / Chapter 5. --- RESULTS --- p.66 / Chapter 5.1 --- Analysis of vitamin D3 standard / Chapter 5.2 --- "Analysis of 1α,25-dihydroxyvitamin D3 standard" / Chapter 5.3 --- Separation of vitamin D3 metabolites / Chapter 5.4 --- "Analysis of lα,25-dihydroxyvitamin D3 in serum samples" / Chapter 5.5 --- Study on hypercalcaemia of tuberculosis / Chapter 6. --- DISCUSSIONS --- p.118 / Chapter 6.1 --- Derivatization / Chapter 6.2 --- Optimization of GC-MS parameters / Chapter 6.3 --- Sample pre-treatment / Chapter 6.4 --- "GC-MS analysis of serum lα,25-dihydroxyvitamin D3" / Chapter 6.5 --- Study on hypercalcaemia of tuberculosis / Chapter 7. --- CONCLUSION --- p.129 / LIST OF ABBREVIATIONS --- p.131 / LIST OF FIGURES --- p.134 / LIST OF TABLES --- p.137 / REFERENCES --- p.139

The plasma vitamin D binding protein (DBP) is an a-glycoprotein, synthesised and secreted by the liver, which binds specifically vitamin D and its metabolites. The DBP molecule, has a single high affinity binding site for its ligands, and is present in blood in concentrations about 1000-fold greater than the sum of all its vitamin D ligands. Previous studies have not found any change in the concentration of DBP related to various derangements in mineral homeostasis. Therefore the general view is that DBP has a passive role in the physiology of vitamin D and its metabolites, and simply acts to solubilise and transport these hydrophobic ligands in the aqueous extracellular fluid. However, differences which have been described in its affinity for various vitamin D metabolites suggest that there have been evolutionary influences on the properties of this protein. Furthermore, plasma DBP concentration has been found to change in response to a number of physiological factors, such as changing sex steroid hormone secretion. The aim of the studies presented in this thesis was to investigate variation in the plasma concentration of the DBP in a range of vertebrate species, and in response to a variety of physiological factors. The results suggest that DBP may have an active role in regulating the bioavailability, and hence the utilisation and metabolism of its ligands. DBP concentration has traditionally been measured using immunological techniques. These techniques, although fast and simple, have a number of draw-backs which can be overcome by the use of assays which rely upon functional aspects of the DBP. A saturation binding assay was modified from those described previously. Using this technique, it was found that both the circulating concentration of the DBP and its affinity for 25-hydroxyvitamin D3 (25(OH)D3) varied significantly among a wide range of species of reptiles and birds. This variation did not reflect phylogenetic relationships among the study species, suggesting that the variation was more likely to be the result of selective pressure in response to individual ecological or physiological circumstance, rather than to random mutation. In support of this, both the plasma concentration of DBP, and its affinity for 25(OH)D3 were significantly associated with a number of ecological factors which might be considered to have some significance to vitamin D and calcium homeostasis. In addition, comparative binding data suggests that the ability of the DBP to bind 25-hydroxyvitamin D2 with equal affinity to 25(OH)D3 is an evolutionary innovation of mammalian vertebrates. In order to extend the idea of genetic variation in the concentration and affinity of plasma DBP, two strains of broiler (meat-type) chickens were studied. It was found that both the concentration and the affinity of plasma DBP for 25(OH)D3 was characteristic for each strain, emphasising the sensitivity of DBP to genetic variation. A number of factors have been found to modulate the genetically determined plasma concentration of DBP. Deficiencies of dietary protein and dietary energy, and variation in concentrations of sex steroids were found to affect the circulating concentration of DBP. However, species differences were still apparent, suggesting that the sensitivity of DBP to these physiological modifiers may have developed independently in different species, and may be secondary to genetic determinants of DBP properties. The plasma DBP concentration and specific binding affinity both determine the availability of its ligands for cellular uptake. It is likely that this process is complex, and involves a combination of protein mediated and non-mediated uptake events. This makes DBP a potentially important determinant of the biological actions of its ligands. The studies in this thesis have produced two main lines of argument supporting an active role for DBP in the regulation of vitamin D metabolism and utilisation. The first is that genetic variation in the properties of plasma DBP appears to be genetically determined, and is selected for, both at the between-species, and the within-species level, than it is to random mutation. Secondly, the ability of physiological and environmental factors to modify the circulating concentration of DBP suggests that this protein is responsive to homeostatic processes. It is proposed that DBP is an active regulator of the physiological economy of vitamin D and its metabolites by being itself regulated by a number of genetic and non-genetic factors.

Thesis (M.S.)--University of Wyoming, 2008. / Title from PDF title page (viewed on Dec. 4, 2009). Includes bibliographical references (p. 75-88).

Despite the medical advances in recent decades, cardiovascular disease (CVD) remains one of the leading causes of mortality in most developing countries. Ongoing efforts have been focused on evaluating new strategies targeting on novel risk factors. Vitamin D deficiency, a previously neglected condition, has recently attracted much attention from the scientific community with its potential extra-skeletal effects. There is accumulating evidence from epidemiological studies that a suboptimal 25-hydroxyvitamin D [25(OH)D] level is associated with all-cause and cardiovascular mortality, increased risk of coronary heart disease, stroke and peripheral vascular disease, and various traditional CVD risk factors including hypertension, diabetes mellitus (DM) and metabolic syndrome. Several theories have been proposed to explain these relationships but none receive universal recognition. There is recent laboratory evidence that vitamin D may exert specific effects in patients with DM. However, relationships between vitamin D deficiency and supplementation on vascular function in this group of patients are unclear. In this dissertation, I sought to explore the effects of vitamin D deficiency on vascular function in patients with type II DM in a cross-sectional study. In the later part, the results of a randomized controlled trial investigating the effects of daily vitamin D supplementation in type II DM patients are presented and discussed. The cross-sectional study (Chapter 3) investigated the association of vitamin D status with endothelial function as measured by brachial flow-mediated dilation (FMD) and circulating endothelial progenitor cell (EPC) numbers in 280 patients with type II DM. The results showed that suboptimal vitamin D status was more common among patients with DM. Furthermore, patients with vitamin D deficiency had significantly lower brachial FMD (mean difference = -1.43%, 95% CI: -2.31 to -0.55, P = 0.001) and CD133/KDR+ EPC counts (mean difference = -0.12%, 95% CI: -0.21 to -0.02, P = 0.022) than those with sufficient vitamin D after adjustment for age, sex and cardiovascular risk factors, including HbA1c levels. Based on these positive results, the objectives of the randomized controlled trial (Chapter 4) were to study and confirm the effects of daily oral vitamin D supplementation on the vascular function in this group of patients. Over a 12-week period, 100 DM patients with suboptimal vitamin D status were randomized to receive 5,000 IU/day vitamin D or placebo. There were no reported adverse events including hypercalcemia, although a slight increase in serum ionized calcium (treatment effect 0.037 mmol/L, P = 0.018) was recorded in the vitamin D group. Despite a significant improvement in serum 25(OH)D in the treatment group, supplementation of vitamin D did not result in any significant improvement in vascular function as determined by FMD, circulating EPC count or arterial stiffness (all P > 0.05). Furthermore, the serum level of high-sensitivity C-reactive protein, oxidative stress markers, low- and high-density lipoprotein and glycated haemoglobin were also similar between two groups (all P > 0.05). The results of this study did not support a therapeutic role of supplementation with vitamin D for cardiovascular benefits. In conclusion, the results of these studies demonstrated that deficiency of vitamin D was associated with worse vascular function in patients with type II DM. However, vitamin D supplementation did not result in any significant benefits on vascular function or improvement in traditional CVD risk factors in DM patients. Further large clinical trials on vitamin D supplementation in patients with DM using clinical outcomes rather than surrogate CVD markers are necessary to confirm its benefits. / published_or_final_version / Medicine / Master / Master of Research in Medicine

The plasma vitamin D binding protein (DBP) is an a-glycoprotein, synthesised and secreted by the liver, which binds specifically vitamin D and its metabolites. The DBP molecule, has a single high affinity binding site for its ligands, and is present in blood in concentrations about 1000-fold greater than the sum of all its vitamin D ligands. Previous studies have not found any change in the concentration of DBP related to various derangements in mineral homeostasis. Therefore the general view is that DBP has a passive role in the physiology of vitamin D and its metabolites, and simply acts to solubilise and transport these hydrophobic ligands in the aqueous extracellular fluid. However, differences which have been described in its affinity for various vitamin D metabolites suggest that there have been evolutionary influences on the properties of this protein. Furthermore, plasma DBP concentration has been found to change in response to a number of physiological factors, such as changing sex steroid hormone secretion. The aim of the studies presented in this thesis was to investigate variation in the plasma concentration of the DBP in a range of vertebrate species, and in response to a variety of physiological factors. The results suggest that DBP may have an active role in regulating the bioavailability, and hence the utilisation and metabolism of its ligands. DBP concentration has traditionally been measured using immunological techniques. These techniques, although fast and simple, have a number of draw-backs which can be overcome by the use of assays which rely upon functional aspects of the DBP. A saturation binding assay was modified from those described previously. Using this technique, it was found that both the circulating concentration of the DBP and its affinity for 25-hydroxyvitamin D3 (25(OH)D3) varied significantly among a wide range of species of reptiles and birds. This variation did not reflect phylogenetic relationships among the study species, suggesting that the variation was more likely to be the result of selective pressure in response to individual ecological or physiological circumstance, rather than to random mutation. In support of this, both the plasma concentration of DBP, and its affinity for 25(OH)D3 were significantly associated with a number of ecological factors which might be considered to have some significance to vitamin D and calcium homeostasis. In addition, comparative binding data suggests that the ability of the DBP to bind 25-hydroxyvitamin D2 with equal affinity to 25(OH)D3 is an evolutionary innovation of mammalian vertebrates. In order to extend the idea of genetic variation in the concentration and affinity of plasma DBP, two strains of broiler (meat-type) chickens were studied. It was found that both the concentration and the affinity of plasma DBP for 25(OH)D3 was characteristic for each strain, emphasising the sensitivity of DBP to genetic variation. A number of factors have been found to modulate the genetically determined plasma concentration of DBP. Deficiencies of dietary protein and dietary energy, and variation in concentrations of sex steroids were found to affect the circulating concentration of DBP. However, species differences were still apparent, suggesting that the sensitivity of DBP to these physiological modifiers may have developed independently in different species, and may be secondary to genetic determinants of DBP properties. The plasma DBP concentration and specific binding affinity both determine the availability of its ligands for cellular uptake. It is likely that this process is complex, and involves a combination of protein mediated and non-mediated uptake events. This makes DBP a potentially important determinant of the biological actions of its ligands. The studies in this thesis have produced two main lines of argument supporting an active role for DBP in the regulation of vitamin D metabolism and utilisation. The first is that genetic variation in the properties of plasma DBP appears to be genetically determined, and is selected for, both at the between-species, and the within-species level, than it is to random mutation. Secondly, the ability of physiological and environmental factors to modify the circulating concentration of DBP suggests that this protein is responsive to homeostatic processes. It is proposed that DBP is an active regulator of the physiological economy of vitamin D and its metabolites by being itself regulated by a number of genetic and non-genetic factors.

Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 2003? / Includes bibliographical references (leaves 226-273.). Also available in an electronic version.

Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 2002. / Includes bibliographical references. Also available in a print form.