admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

Vitamin D deficiency.

Vitamin D is a precursor of the steroid hormone calcitriol that is crucial for bone and mineral metabolism. Both the high prevalence of vitamin D deficiency in the general population and the identification of the vitamin D receptor in the heart and blood vessels raised interest in the potential cardiovascular effects of vitamin D. Experimental studies have demonstrated various cardiovascular protective actions of vitamin D, but vitamin D intoxication in animals is known to induce vascular calcification. In meta-analyses of epidemiological studies, vitamin D deficiency is associated with an increased cardiovascular risk. Findings from Mendelian randomization studies and randomized, controlled trials (RCTs) do not indicate significant effects of a general vitamin D supplementation on cardiovascular outcomes. Previous RCTs, however, were not adequately designed to address extraskeletal events, and did not focus on vitamin D-deficient individuals. Therefore, currently available evidence does not support cardiovascular benefits or harms of vitamin D supplementation with the commonly used doses, and whether vitamin D has cardiovascular effects in individuals with overt vitamin D deficiency remains to be evaluated. Here, we provide an update on clinical studies on vitamin D and cardiovascular risk, discuss ongoing vitamin D research, and consider the management of vitamin D deficiency from a cardiovascular health perspective.

Vitamin D and cardiovascular disease prevention

Pancreatic islets of Langerhans contain several specialized endocrine cell types, which are commonly identified by the expression of single marker genes. However, the established marker genes cannot capture the complete spectrum of cellular heterogeneity in human pancreatic islets, and existing bulk transcriptome datasets provide averages across several cell populations. To dissect the cellular composition of the human pancreatic islet and to establish transcriptomes for all major cell types, we performed single-cell RNA sequencing on 70 cells sorted from human primary tissue. We used this dataset to validate previously described marker genes at the single-cell level and to identify specifically expressed transcription factors for all islet cell subtypes. All data are available for browsing and download, thus establishing a useful resource of single-cell expression profiles for endocrine cells in human pancreatic islets.

/pdf/single-cell-transcriptomes-reveal-characteristic-features-of-36e0pdhynl.pdf

Single-cell transcriptomes reveal characteristic features of human pancreatic islet cell types.

Vitamin D and all its metabolites are bound to a specific vitamin D binding protein, DBP. This protein was originally first discovered by its worldwide polymorphism and called Group-specific Component (GC). We now know that DBP and GC are the same protein and appeared early in the evolution of vertebrates. DBP is genetically the oldest member of the albuminoid family (including albumin, α-fetoprotein and afamin, all involved in transport of fatty acids or hormones). DBP has a single binding site for all vitamin D metabolites and has a high affinity for 25OHD and 1,25(OH)2D, thereby creating a large pool of circulating 25OHD, which prevents rapid vitamin D deficiency. DBP of higher vertebrates (not amphibians or reptiles) binds with very high affinity actin, thereby preventing the formation of polymeric actin fibrils in the circulation after tissue damage. Megalin is a cargo receptor and is together with cubilin needed to reabsorb DBP or the DBP-25OHD complex, thereby preventing the urinary loss of these proteins and 25OHD. The total concentrations of 25OHD and 1,25(OH)2D in DBP null mice or humans are extremely low but calcium and bone homeostasis remain normal. This is the strongest argument for claiming that the "free hormone hypothesis" also applies to the vitamin D hormone, 1,25(OH)2D. DBP also transports fatty acids, and can play a role in the immune system. DBP is genetically very polymorphic with three frequent alleles (DBP/GC 1f, 1s, and 2) but in total more than 120 different variants but its health consequences, if any, are not understood. A standardization of DBP assays is essential to further explore the role of DBP in physiology and diseases.

/pdf/vitamin-d-binding-protein-a-historic-overview-3wk6ngjf1l.pdf

Vitamin D Binding Protein: A Historic Overview.

Observational studies have indicated an inverse association between vitamin D levels and the risk of diabetes, yet evidence from population interventions remains inconsistent. PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov were searched up to September 2017. Data from studies regarding serum 25(OH)D, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were pooled. Twenty studies (n = 2703) were included in the meta-analysis. Vitamin D supplementation resulted in a significant improvement in serum 25(OH)D levels (weighted mean difference (WMD) = 33.98; 95%CI: 24.60–43.37) and HOMA-IR (standardized mean difference (SMD) = −0.57; 95%CI: −1.09~−0.04), but not in other outcomes. However, preferred changes were observed in subgroups as follows: short-term (WMDFBG = −8.44; 95%CI: −12.72~−4.15), high dose (WMDFBG = −8.70; 95%CI: −12.96~−4.44), non-obese (SMDFasting insulin = −1.80; 95%CI: −2.66~−0.95), Middle Easterners (WMDFBG = −10.43; 95%CI: −14.80~−6.06), baseline vitamin D deficient individuals (WMDFBG = −5.77; 95%CI: −10.48~−1.05) and well-controlled HbA1c individuals (WMDFBG = −4.09; 95%CI: −15.44~7.27). Vitamin D supplementation was shown to increase serum 25(OH)D and reduce insulin resistance effectively. This effect was especially prominent when vitamin D was given in large doses and for a short period of time, and to patients who were non-obese, Middle Eastern, vitamin D deficient, or with optimal glycemic control at baseline.

https://www.mdpi.com/2072-6643/10/3/375/pdf

The Effect of Vitamin D Supplementation on Glycemic Control in Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis

Objective Previous studies on the association between vitamin D binding protein (DBP) polymorphisms and the risk of type 2 diabetes mellitus (T2DM) have produced conflicting results. The purpose of this meta-analysis was to examine whether DBP polymorphisms are associated with the risk of T2DM. Design Systematic review and meta-analysis. Methods All eligible studies were searched and acquired from the Cochrane, Pubmed, ISI, CNKI (Chinese) and Wanfang (Chinese) databases. ORs with corresponding 95% CIs were computed to estimate the association between DBP polymorphisms and T2DM. In addition, heterogeneity test, meta-regression and sensitivity analysis were also conducted. Results Six studies, which included 1191 cases and 882 controls, met the inclusion criteria and were included in the meta-analysis. The results showed that no significant associations were found between codon 416 and codon 420 polymorphisms in the DBP and the risk of T2DM in the overall analyses. In stratified analysis, significant associations between the codon 420 polymorphism and T2DM were found in Asians (allele Lys vs Thr: OR (95% CI) 1.49 (1.19 to 1.85), genotype Lys/Thr versus Thr/Thr: OR (95% CI) 1.80 (1.36 to 2.38), and Lys/Thr+Lys/Lys versus Thr/Thr: OR (95% CI) 1.81 (1.37 to 2.39), respectively) but not in Caucasians. For the codon 416, the significant association with T2DM was also detected in Asians (genotype Glu/Asp+Glu/Glu vs Asp/Asp: OR (95% CI) 1.36 (1.04 to 1.78)) but not in Caucasians. Conclusions This meta-analysis demonstrated that the DBP polymorphism was moderately associated with increased susceptibility to T2DM in Asians, but a similar association was not found in Caucasians. It suggested that ethnicity might be the potential factor associated with heterogeneity.

https://bmjopen.bmj.com/content/bmjopen/4/11/e005617.full.pdf

Association of the vitamin D binding protein polymorphisms with the risk of type 2 diabetes mellitus: a meta-analysis.

Background: Vitamin D receptor (〞VDR〞) genetic polymorphisms are considered to be associated with type 2 diabetes mellitus (T2DM), but this is inconclusive. The aim of this study is to quantify the association between polymorphisms of 〞Bsm〞I and 〞Fok〞I in the 〞VDR〞 gene and T2DM risk through literature review. Methods: Original articles published from 1999 to June 2014 were discovered through PubMed, ISI Web of Science, China National Knowledge Infrastructure, Chinese Wanfang Database, and the Chinese Biomedical Literature Database. The pooled odds ratios (〞ORs〞) with 95% confidence intervals (〞CIs〞) were calculated with software STATA version 12.0. Results: Twenty-three articles containing 30 case–control studies were included. The association between the 〞Bsm〞I polymorphism and T2DM was weak in two genetic models (Bb vs bb and BB+Bb vs bb). The subgroup analysis showed that this association was only found in the studies with a small sample size (＜200).A strong association between 〞Fok〞I polymorphism and T2DM indicated that this gene polymorphism was possibly a risk factor for T2DM (ff vs FF: OR=1.57, 95% CI: 1.28-1.93, 〞p〞＜0.001; Ff vs FF: OR=1.54, 95% CI: 1.31-1.81, 〞p〞＜0.001; ff+Ff vs FF: OR=1.57, 95% CI: 1.35-1.83, 〞p〞＜0.001), especially in Chinese populations. Conclusion: More reliable conclusions about associations between Vitamin D receptor (〞VDR〞) genetic polymorphisms and T2DM will depend on studies with larger sample size and by ethnicity.

The genetic polymorphisms in vitamin D receptor and the risk of type 2 diabetes mellitus: an updated meta-analysis.

The factors affecting the reproducibility of micro-volume DNA mass quantification in Nanodrop 2000 spectrophotometer

BACKGROUND Vitamin D and the vitamin D receptor (VDR) are associated with susceptibility to type 2 diabetes mellitus (T2DM). The purpose of the present study was to screen more single nucleotide polymorphisms (SNPs) of VDR and assess their effects on the risk of T2DM in Han Chinese. METHOD Four SNPs were genotyped in 1191 individuals (397 cases, 794 controls). Allele frequencies and genotype distributions were analyzed. Effects were investigated by evaluating genotype distribution with regard to phenotypes, insulin resistance, and β-cell function. Haplotype analysis and gene risk score (GRS) were used to evaluate the combined and additive roles of VDR SNPs on T2DM pathogenesis. RESULTS There was a significant association between rs739837 and T2DM in two models and allele frequency distribution. The novel locus rs2239179 differed significantly between cases and controls, especially in males and those aged >55 years, in three models and allele frequency distribution. The TT genotype of rs739837 was associated with higher triglyceride than GG and TG genotypes, and higher total cholesterol levels than the GG genotype. Compared with the GTGA haplotype, the GCGG haplotype reduced the risk of T2DM. Trend Chi-squared tests showed that there was significant association between the weighted GRS and the risk of T2DM (Ptrend  = 0.034). CONCLUSION This study provides novel evidence that rs739837 is associated with lipid metabolism in T2DM patients. The rs739837 and rs2239179 SNPs were associated with the risk of T2DM in Han Chinese. The VDR SNPs had combined and additive effects on the risk of T2DM.

Study and evaluation the impact of vitamin D receptor variants on the risk of type 2 diabetes mellitus in Han Chinese

Serum vitamin D deficiency and vitamin D receptor gene polymorphism are associated with increased risk of cardiovascular disease in a Chinese rural population.

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