Vitamin D3 metabolite ratio as an indicator of vitamin D status and its association with diabetes complications.

BACKGROUND: Vitamin D deficiency is diagnosed by total serum 25-hydroxyvitamin D (25(OH)D) concentration and is associated with poor health and increased mortality; however, some populations have low 25(OH) D concentrations without manifestations of vitamin D deficiency. The Vitamin D Metabolite Ratio (VMR) has been suggested as a superior indicator of vitamin D status. Therefore, VMR was determined in a population with type 2 diabetes at high risk for vitamin D deficiency and correlated with diabetic complications. RESEARCH DESIGN AND METHODS: Four hundred sisty patients with type 2 diabetes (T2D) were recruited, all were vitamin D3 supplement naive. Plasma concentration of 25-hydroxyvitamin D3 (25(OH)D3) and its metabolites 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) and its epimer, 3-epi-25-hydroxyvitamin D3 (3-epi-25(OH)D3), were measured by LC-MS/MS analysis. VMR-1 was calculated as a ratio of 24,25(OH)2D3:25(OH)D3; VMR-2 as a ratio of 1,25(OH)2D3:25(OH)D3; VMR-3 was calculated as a ratio of 3-epi-25(OH)D3: 25(OH)D3. RESULTS: An association means that there were significant differences between the ratios found for those with versus those without the various diabetic complications studied. VMR-1 was associated with diabetic retinopathy (p = 0.001) and peripheral artery disease (p = 0.012); VMR-2 associated with hypertension (p < 0.001), dyslipidemia (p < 0.001), diabetic retinopathy (p < 0.001), diabetic neuropathy (p < 0.001), coronary artery disease (p = 0.001) and stroke (p < 0.05). VMR-3 associated with hypertension (p < 0.05), dyslipidemia (p < 0.001) and coronary artery disease (p < 0.05). CONCLUSIONS: In this cross sectional study, whilst not causal, VMR-2 was shown to be the superior predictor of diabetic and cardiovascular complications though not demonstrative of causality in this cross-sectional study population over VMR-1, VMR-3 and the individual vitamin D concentration measurements; VMR-2 associated with both microvascular and cardiovascular indices and therefore may have utility in predicting the development of diabetic complications.

Association of vitamin D2 and D3 with type 2 diabetes complications.

AIMS: Vitamin D measurement is a composite of vitamin D2 (25(OH)D2) and D3 (25(OH)D3) levels, and its deficiency is associated with the development of type 2 diabetes (T2DM) and diabetic complications; vitamin D deficiency may be treated with vitamin D2 supplements. This study was undertaken to determine if vitamin D2 and D3 levels differed between those with and without T2DM in this Middle Eastern population, and the relationship between diabetic microvascular complications and vitamin D2 and vitamin D3 levels in subjects with T2DM. METHODS: Four hundred ninety-six Qatari subjects, 274 with and 222 without T2DM participated in the study. Plasma levels of total vitamin D2 and D3 were measured by LC-MS/MS analysis. RESULTS: All subjects were taking vitamin D2 and none were taking D3 supplements. Vitamin D2 levels were higher in diabetics, particularly in females, and higher levels were associated with hypertension and dyslipidemia in the diabetic subjects (p < 0.001), but were not related to diabetic retinopathy or nephropathy. Vitamin D3 levels measured in the same subjects were lower in diabetics, particularly in females (p < 0.001), were unrelated to dyslipidemia or hypertension, but were associated with retinopathy (p < 0.014). Neither vitamin D2 nor vitamin D3 were associated with neuropathy. For those subjects with hypertension, dyslipidemia, retinopathy or neuropathy, comparison of highest with lowest tertiles for vitamin D2 and vitamin D3 showed no difference. CONCLUSIONS: In this Qatari cohort, vitamin D2 was associated with hypertension and dyslipidemia, whilst vitamin D3 levels were associated with diabetic retinopathy. Vitamin D2 levels were higher, whilst vitamin D3 were lower in diabetics and females, likely due to ingestion of vitamin D2 supplements.

Relationship between total vitamin D metabolites and complications in patients with type 2 diabetes.

In our previous study, it was shown that endogenous vitamin D3 and its metabolites are associated with diabetic microvascular complications and cardiovascular risk factors. The aim of the present study was to determine if the relationship between total vitamin D (vitamin D2 supplements plus endogenous vitamin D3) was a better predictor of complications in type 2 diabetes (T2DM). A total of 460 patients with T2DM participated in the present cross-sectional study. Plasma levels of total vitamin D and its metabolites (1,25-dihydroxyvitamin D (1,25(OH)D), 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)D) were measured by isotope-dilution liquid chromatography tandem mass spectrometry analysis. 1,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 were associated with diabetic retinopathy and coronary artery disease, but total 1,25-dihydroxyvitamin D and total 25-hydroxyvitamin D levels were not statistically associated with any complications. Total 1,25-dihydroxyvitamin D showed the same positive association as 1,25-dihydroxyvitamin D3 for hypertension and dyslipidemia, and total 25-hydroxyvitamin D showed the same positive association as 25-hydroxyvitamin D3 for dyslipidemia. Total 24,25-dihydroxyvitamin D showed the same positive association only with dyslipidemia as did 24,25-dihydroxyvitamin D3. However, total 25-hydroxyvitamin D was associated with hypertension, whereas 25-hydroxyvitamin D3 was not. Vitamin D3 metabolites were associated with diabetic retinopathy, whereas total vitamin D levels were not, suggesting that endogenous vitamin D3 metabolites are a better measure of diabetic microvascular complications. However, both total vitamin D and vitamin D3 metabolites were associated with cardiovascular risk factors in patients with type 2 diabetes.

Association of Differing Qatari Genotypes with Vitamin D Metabolites.

OBJECTIVE: Genetic studies have identified four Qatari genotypes: Q1 Arab, Bedouin; Q2 Asian/Persian; Q3 African; and a fourth admixed group not fitting into the previous 3 groups. This study was undertaken to determine if there was an increased risk of deficiency of vitamin D and its metabolites associated with differing genotypes, perhaps due to genetic differences in skin pigmentation. METHODS: 398 Qatari subjects (220 type 2 diabetes and 178 controls) had their genotype determined by Affymetrix 500 k SNP arrays. Total values of 1,25-dihydroxyvitamin D (1,25(OH)2D), 25-hydroxyvitamin D (25(OH)D), 24,25-dihydroxyvitamin D (24,25(OH)2D), and 25-hydroxy-3epi-vitamin D (3epi-25(OH)D) concentrations were measured by the LC-MS/MS analysis. RESULTS: The distribution was as follows: 164 (41.2%) genotyped Q1, 149 (37.4%) genotyped Q2, 31 (7.8%) genotyped Q3, and 54 (13.6%) genotyped "admixed." Median levels of 25(OH)D and 3epi-25(OH)D did not differ across Q1, Q2, Q3, and "admixed" genotypes, respectively. 1,25(OH)2D levels were lower (p < 0.04) between Q2 and the admixed groups, and 24,25(OH)2D levels were lower (p < 0.05) between Q1 and the admixed groups. Vitamin D metabolite levels were lower in females for 25(OH)D, 1,25(OH)2D (p < 0.001), and 24,25(OH)2D (p < 0.006), but 3epi-25(OH)D did not differ (p < 0.26). Diabetes prevalence was not different between genotypes. Total 1,25(OH)2D (p < 0.001), total 24,25(OH)2D (p < 0.001), and total 3epi-25(OH)D (p < 0.005) were all significantly lower in diabetes patients compared to controls whilst the total 25(OH)D was higher in diabetes than controls (p < 0.001). CONCLUSION: Whilst 25(OH)D levels did not differ between genotype groups, 1,25(OH)2D and 24,25(OH)2D were lower in the admixed group, suggesting that there are genetic differences in vitamin D metabolism that may be of importance in a population that may allow a more targeted approach to vitamin D replacement. This may be of specific importance in vitamin D replacement strategies with the Q2 genotype requiring less, and the other genotypes requiring more to increase 1,25(OH)2D. Whilst overall the group was vitamin D deficient, total 25(OH)D was higher in diabetes, but 1,25(OH)2D, 24,25(OH)2D, and 3epi-25(OH)D were lower in diabetes that did not affect the relationship to genotype.

Association of vitamin D3 and its metabolites in patients with and without type 2 diabetes and their relationship to diabetes complications.

BACKGROUND: Epidemiological studies have suggested that vitamin D deficiency is associated with the development of type 2 diabetes (T2DM) and is related to diabetes complications. This study was undertaken to determine the relationship between diabetes complications and cardiovascular risk factors with vitamin D3 and its metabolites: 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), 25-hydroxyvitamin D3 (25(OH)D3), 24,25-dihydroxyvitamin D3 (24,25(OH)2D3); and 25-hydroxy-3epi-vitamin D3 (3epi25(OH)D3). METHODS: 750 Qatari subjects, 460 (61.3%) with and 290 (38.7%) without T2DM, who were not taking vitamin D3 supplements, participated in this cross-sectional, observational study. Plasma concentrations of vitamin D3 and its metabolites were measured by liquid chromatography tandem mass spectrometry analysis. RESULTS: T2DM subjects had lower concentrations of all vitamin D3 metabolites (p < 0.001) except 3epi25(OH)D3 (p < 0.071). Males had higher concentrations of all vitamin D3 metabolites (p < 0.001). In the T2DM subjects, lower 25(OH)D3 was associated with retinopathy (p < 0.03) and dyslipidemia (p < 0.04), but not neuropathy or vascular complications; lower 1,25(OH)2D3 was associated with hypertension (p < 0.009), dyslipidemia (p < 0.003) and retinopathy (p < 0.006), and coronary artery disease (p < 0.012), but not neuropathy; lower 24,25(OH)2D3 concentrations were associated with dyslipidemia alone (p < 0.019); 3epi25(OH)D3 associated with diabetic neuropathy alone (p < 0.029). In nondiabetics, 25(OH)D3, 1,25(OH)2D3 and 24,25(OH)2D3 were associated with dyslipidemia (p < 0.001, p < 0.001, p < 0.015, respectively) and lower 1,25(OH)2D3 was associated with hypertension (p < 0.001). Spearman's correlation showed 1,25(OH)2D3 to be negatively correlated to age and diabetes duration. CONCLUSIONS: Different diabetes complications were associated with differing vitamin D parameters, with diabetic retinopathy related to lower 25(OH)D3 and 1,25(OH)2D3 levels, hypertension significantly associated with lower 1,25(OH)2D3, while dyslipidemia was associated with lower 25(OH)D3, 1,25(OH)2D3 and 24,25(OH)2D3. While 25(OH)D metabolites were lower in females, there was not an exaggeration in complications.

An overview of the spiritual importances of end-of-life care among the five major faiths of the United Kingdom.

For many who pertain to particular theological paradigms, their faith cannot be compartmentalised, but is mobilised to inform all aspects of their being, most notably their ethical and moral persuasions. As clinicians, the concept that there are good and bad deaths is already known; understanding the origin and depth of non-physical suffering, and aiming to alleviate it is not possible without learning the individual experiences and beliefs that go with it. Spiritual care forms a fundamental consideration in the endeavor to address the holistic experience of those patients receiving palliative care. Good palliative care seeks to promote the wellbeing and priorities of those with faltering health in a way that continues to support individualised notions of self-determination. The last few decades have resulted in a multicultural and multi-ethnic patient population. Addressing the spiritual and physical needs of patients allows healthcare professionals to deliver truly holistic care. Exploring and understanding the specific nuances of the five major religions of the UK provides healthcare professionals the opportunity to comfort the religiously observant patient at the end of life.

Documenting the process of patient decision making: a review of the development of the law on consent.

The doctor's role involves helping patients to understand their condition, including the anticipated benefits and risks of proposed treatments or omissions to treat. In order to treat, doctors require consent from patients but the duty to advise is equally strong if conservative management is appropriate. The recent judgement in the case of Montgomery has set a precedent for patient autonomy. However, doctors are still required to judge what risks they should disclose in their reasonable assessment of that patient and their specific situation. The General Medical Council reflects a consensus that the empowered autonomous patient is more likely to be satisfied with their clinical outcome than the passive victim of medical paternalism. Doctors, regardless of specialty, must counsel their patients adequately, paying particular attention to identifying material risks that are likely to be significant to their case.