ResearchPad - metabolic-disorders https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Collagen methionine sulfoxide and glucuronidine/LW-1 are markers of coronary artery disease in long-term survivors with type 1 diabetes. The Dialong study]]> https://www.researchpad.co/article/elastic_article_13877 Type 1 diabetes is a risk factor for coronary heart disease. The underlying mechanism behind the accelerated atherosclerosis formation is not fully understood but may be related to the formation of oxidation products and advanced glycation end-products (AGEs). We aimed to examine the associations between the collagen oxidation product methionine sulfoxide; the collagen AGEs methylglyoxal hydroimidazolone (MG-H1), glucosepane, pentosidine, glucuronidine/LW-1; and serum receptors for AGE (RAGE) with measures of coronary artery disease in patients with long-term type 1 diabetes.MethodsIn this cross-sectional study, 99 participants with type 1 diabetes of ≥ 45-year duration and 63 controls without diabetes had either established coronary heart disease (CHD) or underwent Computed Tomography Coronary Angiography (CTCA) measuring total, calcified and soft/mixed plaque volume. Skin collagen methionine sulfoxide and AGEs were measured by liquid chromatography-mass spectrometry and serum sRAGE/esRAGE by ELISA.ResultsIn the diabetes group, low levels of methionine sulfoxide (adjusted for age, sex and mean HbA1c) were associated with normal coronary arteries, OR 0.48 (95% CI 0.27–0.88). Glucuronidine/LW-1 was associated with established CHD, OR 2.0 (1.16–3.49). MG-H1 and glucuronidine/LW-1 correlated with calcified plaque volume (r = 0.23–0.28, p<0.05), while pentosidine correlated with soft/mixed plaque volume (r = 0.29, p = 0.008), also in the adjusted analysis.ConclusionsLow levels of collagen-bound methionine sulfoxide were associated with normal coronary arteries while glucuronidine/LW-1 was positively associated with established CHD in long-term type 1 diabetes, suggesting a role for metabolic and oxidative stress in the formation of atherosclerosis in diabetes. ]]> <![CDATA[Fruit and vegetable consumption in Europe according to gender, educational attainment and regional affiliation—A cross-sectional study in 21 European countries]]> https://www.researchpad.co/article/elastic_article_13846 The purpose of the present study was to examine fruit and vegetable consumption according to gender, educational attainment and regional affiliation in Europe.DesignCross-sectional study.Setting21 European countries.Participants37 672 adults participating in the 7th round of the European Social Survey.Main outcome measuresFruit and vegetable consumption was measured using two single frequency questions. Responses were dichotomized into low (<once a day) and high (≥once a day) consumption. The association between consumption of fruit and vegetables and gender, educational level, regional affiliation was examined using logistic regression analyses.ResultsOverall, females showed increased odds of consuming fruit (OR 1.71 (95%CI:1.62, 1.79) and vegetable (1.59 (1.51, 1.67)) compared to males and high educated participants showed increased odds of consuming fruit (1.53 (1.43, 1.63)) and vegetables (1.86 (1.74, 2.00)) compared to low educated participants. Our results also showed that participants living in Eastern Europe had the lowest odds of consuming fruit and vegetables, whereas participants from Southern- and Northern Europe had the highest odds of consuming fruit and vegetables, respectively. Results from interaction analyses confirmed the positive association between fruit and vegetable consumption and educational level, although for some European regions, decreased odds of fruit and vegetables was observed among medium educated participants compared to those with low education.ConclusionsOverall, the present study showed that being female and having a high education were associated with increased consumption of fruit and vegetables. However, the direction and strength of these relationships depends on regional affiliations. ]]> <![CDATA[Estimating the potential impact of behavioral public health interventions nationally while maintaining agreement with global patterns on relative risks]]> https://www.researchpad.co/article/elastic_article_13880 This paper introduces a novel method to evaluate the local impact of behavioral scenarios on disease prevalence and burden with representative individual level data while ensuring that the model is in agreement with the qualitative patterns of global relative risk (RR) estimates. The method is used to estimate the impact of behavioral scenarios on the burden of disease due to ischemic heart disease (IHD) and diabetes in the Turkish adult population.MethodsDisease specific Hierarchical Bayes (HB) models estimate the individual disease probability as a function of behaviors, demographics, socio-economics and other controls, where constraints are specified based on the global RR estimates. The simulator combines the counterfactual disease probability estimates with disability adjusted life year (DALY)-per-prevalent-case estimates and rolls up to the targeted population level, thus reflecting the local joint distribution of exposures. The Global Burden of Disease (GBD) 2016 study meta-analysis results guide the analysis of the Turkish National Health Surveys (2008 to 2016) that contain more than 90 thousand observations.FindingsThe proposed Qualitative Informative HB models do not sacrifice predictive accuracy versus benchmarks (logistic regression and HB models with non-informative and numerical informative priors) while agreeing with the global patterns. In the Turkish adult population, Increasing Physical Activity reduces the DALYs substantially for both IHD by 8.6% (6.4% 11.2%), and Diabetes by 8.1% (5.8% 10.6%), (90% uncertainty intervals). Eliminating Smoking and Second-hand Smoke predominantly decreases the IHD burden 13.1% (10.4% 15.8%) versus Diabetes 2.8% (1.1% 4.6%). Increasing Fruit and Vegetable Consumption, on the other hand, reduces IHD DALYs by 4.1% (2.8% 5.4%) while not improving the Diabetes burden 0.1% (0% 0.1%).ConclusionWhile the national RR estimates are in qualitative agreement with the global patterns, the scenario impact estimates are markedly different than the attributable risk estimates from the GBD analysis and allow evaluation of practical scenarios with multiple behaviors. ]]> <![CDATA[Health profile of adult special immigrant visa holders arriving from Iraq and Afghanistan to the United States, 2009–2017: A cross-sectional analysis]]> https://www.researchpad.co/article/elastic_article_13850 Between 2,000 and 19,000 Special Immigrant Visa holders (SIVH) from Iraq and Afghanistan have resettled in the United States annually since 2008.Per the Immigration and Nationality Act, SIVH, like other immigrants and refugees, must be examined by a physician before arriving in the US. Results of these overseas examinations are transmitted by the Centers for Disease Control and Prevention (CDC) to US state and local health departments via CDC’s Electronic Disease Notification system (EDN).Increasing provider knowledge about the health conditions most commonly encountered in SIVH as well as any differences in health conditions between SIVH from Iraq and Afghanistan may facilitate diagnostic screening, examination, and referrals to additional healthcare providers in the US.Information about the health of SIV populations is limited and would be beneficial for US clinicians who see SIVH in their clinics.What did the researchers do and find?In this cross-sectional analysis, we analyzed overseas medical exam data in CDC’s EDN for 19,167 SIV Iraqi and Afghan adults who resettled to the United States from April 2009 through December 2017.Among all SIVH, 56.5% were overweight or had obesity, 2.4% reported hypertension, 1.1% reported diabetes, and 19.4% reported current or previous tobacco use.In general, Iraqi SIVH were more likely to have obesity, diabetes, and be current or former smokers than Afghan SIVH.What do these findings mean?State public health agencies and clinicians screening SIVH should consider screening for diabetes among those with risk factors and prompt referral and management of obesity, hypertension, and smoking.Behavioral risk factor counseling and referral to culturally appropriate chronic disease prevention programs can be initiated at screening visits and subsequently reemphasized with primary care providers and other healthcare professionals.Limitations include the inability to obtain all SIVH records, self-reported medical history of NCDs, and underdiagnosis of NCDs such as hypertension and diabetes because formal laboratory testing for NCDs is not used during overseas medical exams. ]]> <![CDATA[Barriers and facilitating factors in the prevention of diabetes type 2 and gestational diabetes in vulnerable groups: A scoping review]]> https://www.researchpad.co/article/elastic_article_13859 Type 2 diabetes mellitus (T2DM) and gestational diabetes (GDM) are globally on the rise, accompanied by comorbidities and associated health costs. Increased physical activity, healthy nutrition, and weight loss have shown the potential to prevent T2DM/GDM. Despite this, reaching vulnerable groups remains a key challenge. The aim of this scoping review was to identify barriers and facilitating factors in the prevention of T2DM/GDM in vulnerable groups.MethodsWe conducted a systematic literature search in May 2018, updated in September 2019, in several databases (e.g. PubMed, Embase) to identify barriers and facilitating factors in the prevention of T2DM/GDM in vulnerable groups. Two reviewers independently screened the results. Extracted data was charted, categorized, and summarized.ResultsWe included 125 articles. Ninety-eight studies were extracted, and eight categories of barriers and facilitating factors were formed. The most common categories of barriers were limited knowledge, family/friends, and economic factors, and the most common categories of facilitating factors were family/friends, social support, and knowledge.ConclusionThis scoping review identified various barriers and facilitating factors in vulnerable groups. Preventive interventions should consider these barriers and facilitating factors in developing preventive interventions or in adapting existing ones. ]]> <![CDATA[Silencing of LncRNA PVT1 inhibits the proliferation, migration and fibrosis of high glucose-induced mouse mesangial cells via targeting microRNA-93-5p]]> https://www.researchpad.co/article/elastic_article_9222 Objective: The present study aimed to investigate the regulatory role of long non-coding RNA plasmacytoma variant translocation 1 (PVT1) on high glucose (HG)-induced mouse mesangial cells (MMCs).

Methods: PVT1 expression in diabetic nephropathy (DN) mice and HG-induced MMCs was detected by qRT-PCR. EdU and Colony formation, Annexin V-PI staining, Muse cell cycle, Scratch, and Transwell assays were performed to detect the cell proliferation, apoptosis, cell cycle, migration, and invasion, respectively. The contents of fibrosis factors in cell-culture supernatants were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was performed to detect the expression of factors involved in apoptosis, cell cycle, migration and invasion, fibrosis, and PI3K/Akt/mTOR pathway. The targeting relation between miR-93-5p and PVT1 was predicted by StarBase3.0 (an online software for analyzing the targeting relationship) and identified by Dual-luciferase reporter (DLR) assay.

Results: PVT1 was overexpressed in DN kidney tissues and HG-induced MMCs. HG-induced MMCs exhibited significantly increased EdU-positive cells, cell colonies, S and G2/M phase cells, migration and invasion ability, and contents of fibrosis factors, as well as significantly decreased apoptosis rate compared with NG-induced MMCs. HG significantly up-regulated Bcl-2, CyclinD1, CDK4, N-cadherin, vimentin, Col. IV, FN, TGF-β1 and PAI-1, and down-regulated Bax, cleaved caspase-3, cleaved PARP, and E-cadherin in MMCs. Silencing of PVT1 eliminated the effects of HG in MMCs and blocked PI3K/Akt/mTOR pathway. MiR-93-5p was a target of PVT1, which eliminated the effects of PVT1 on HG-induced MMCs.

Conclusions: PVT1 silencing inhibited the proliferation, migration, invasion and fibrosis, promoted the apoptosis, and blocked PI3K/Akt/mTOR pathway in HG-induced MMCs via up-regulating miR-93-5p.

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<![CDATA[Hereditary hemochromatosis disrupts uric acid homeostasis and causes hyperuricemia via altered expression/activity of xanthine oxidase and ABCG2]]> https://www.researchpad.co/article/elastic_article_9170 Hereditary hemochromatosis (HH) is mostly caused by mutations in the iron-regulatory gene HFE. The disease is associated with iron overload, resulting in liver cirrhosis/cancer, cardiomegaly, kidney dysfunction, diabetes, and arthritis. Fe2+-induced oxidative damage is suspected in the etiology of these symptoms. Here we examined, using Hfe−/− mice, whether disruption of uric acid (UA) homeostasis plays any role in HH-associated arthritis. We detected elevated levels of UA in serum and intestine in Hfe−/− mice compared with controls. Though the expression of xanthine oxidase, which generates UA, was not different in liver and intestine between wild type and Hfe−/− mice, the enzymatic activity was higher in Hfe−/− mice. We then examined various transporters involved in UA absorption/excretion. Glut9 expression did not change; however, there was an increase in Mrp4 and a decrease in Abcg2 in Hfe−/− mice. As ABCG2 mediates intestinal excretion of UA and mutations in ABCG2 cause hyperuricemia, we examined the potential connection between iron and ABCG2. We found p53-responsive elements in hABCG2 promoter and confirmed with chromatin immunoprecipitation that p53 binds to this promoter. p53 protein was reduced in Hfe−/− mouse intestine. p53 is a heme-binding protein and p53-heme complex is subjected to proteasomal degradation. We conclude that iron/heme overload in HH increases xanthine oxidase activity and also promotes p53 degradation resulting in decreased ABCG2 expression. As a result, systemic UA production is increased and intestinal excretion of UA via ABCG2 is decreased, causing serum and tissue accumulation of UA, a potential factor in the etiology of HH-associated arthritis.

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<![CDATA[Brazilian vegetarians diet quality markers and comparison with the general population: A nationwide cross-sectional study]]> https://www.researchpad.co/article/elastic_article_7851 Vegetarianism is an increasingly common practice worldwide. Despite good evidence from other countries regarding vegetarians’ diet quality, data from the Brazilian population is still scarce.ObjectiveTo characterize the vegetarian Brazilian population and evaluate their diet quality compared to the general Brazilian population.MethodsWe performed a nationwide cross-sectional study using an online self-administered questionnaire, previously validated for the Brazilian population, to evaluate diet quality markers of vegetarians. The invitation to participate in the survey was spread nationwide, aimed at vegetarian communities. Individuals who considered themselves vegetarians and were at least 18 years old were eligible to participate. The results on regular intake and intake adequacy were compared among vegetarians and between genders using the Pearson’s chi-square test. The body mass index (BMI) were analyzed by the Analysis of Variance (ANOVA) followed by Tukey post-hoc test. The Kolmogorov-Smirnov test verified normality. All analyses considered bilateral hypotheses and a significance level of 5% (p <0.05).ResultsBrazilian vegetarians presented better diet quality markers, such as higher regular weekly intake and adequate daily intake of fruits and vegetables, and lower regular intake of soft drinks when compared to the general Brazilian population. Vegetarians also presented a proportionally higher consumption of natural foods and lower consumption of processed foods. Among vegetarians, a higher proportion of vegans showed positive results regarding diet markers analysis, when compared to vegetarians, pesco-vegetarians, and semi-vegetarians.ConclusionsVegetarians showed better results of diet adequacy when compared to the general population in Brazil, and vegans fared better when compared with other vegetarians. Despite the good results found, a large proportion of the participants still did not achieve the fruits and vegetables daily intake, according to the World Health Organization recommendations. ]]> <![CDATA[Life expectancy and survival analysis of patients with diabetes compared to the non diabetic population in Bulgaria]]> https://www.researchpad.co/article/elastic_article_7723 To evaluate the expected life expectancy in patients with diabetes in Bulgaria and to compare it to the expected life expectancy of the non-diabetic population in the country.MethodsIt is a retrospective observational population study on individuals diagnosed with diabetes, compared to the non-diabetic population in Bulgaria for the period 2012–2015. Data from the national diabetes register and national statistical institute were used to construct life-tables with probability of survival with t-test and Chi Square test. Confounder analysis was done by age, sex, and type of diabetes. All-cause mortality and deaths in diabetic patients were analyzed. Kaplan-Meier survival curves were constructed for each age group and a log-rank analysis was conducted.ResultsAverage life expectancy in the non-diabetic population, patients with Type 1 DM and with Type 2 DM is 74.8; 70.96 and 75.19 years, respectively. For 2012–2015 the mortality in the non-diabetic population remained constant and lower (average—1.48%) compared to type-1 DM (5.25%) and Type-2 (4.27%). Relative risk of death in diabetics was higher overall (12%), after the age of 70 before which the relative risk was higher for the non-diabetic population. This was observed as a trend in all analyzed years.ConclusionPatients with type 2 DM have a longer life-expectancy than patients with type-1 DM and overall Diabetics life expectancy equals that of the non-diabetic population, which could suggest improved disease control and its associated complications in Bulgaria. Male diabetics show slightly longer life expectancy than their counterparts in the non-diabetic population, by a marginal gain of 0.6 years for the entire observed period. Life expectancy in diabetic women increased by 1.3 years, which was not observed in the non-diabetic population. Prevalence of diabetes was higher for women. Improved diabetes control may explain this gain in life; however other studies are needed to confirm this. ]]> <![CDATA[MiR-770-5p facilitates podocyte apoptosis and inflammation in diabetic nephropathy by targeting TIMP3]]> https://www.researchpad.co/article/Nf6861224-ba65-498a-8aad-78abbb68558a Objective: Diabetic nephropathy (DN) is one of the most severe and frequent diabetic complications. MicroRNAs (miRNAs) have been reported to play a vital role in DN pathogenesis. The present study aimed to investigate the molecular mechanism of miR-770-5p in DN.

Methods: Podocyte injury model was established by treating mouse podocytes with high glucose (HG, 33 mM) for 24 h. The levels of miR-770-5p and TIMP3 were examined in kidney tissues and podocytes using quantitative real-time PCR (qRT-PCR). Flow cytometry analysis was applied to detect apoptosis in podocytes. Western blot assay was used to measure the protein levels of B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X (Bax) and tissue inhibitors of metalloproteinase 3 (TIMP3). Enzyme-linked immunosorbent assay (ELISA) was conducted to measure the levels of inflammatory factors. The interaction between miR-770-5p and TIMP3 was determined by MicroT-CDS and luciferase reporter assay.

Results: MiR-770-5p was up-regulated and TIMP3 was down-regulated in DN kidney tissues and HG-stimulated podocytes. Depletion of miR-770-5p suppressed cell apoptosis and the release of pro-inflammatory factors in HG-treated podocytes. Additionally, TIMP3 was a target of miR-770-5p in HG-treated podocytes. TIMP3 inhibited cell apoptosis and inflammation in HG-treated podocytes. Moreover, TIMP3 knockdown alleviated the inhibitory effect of miR-770-5p silencing on podocyte apoptosis and inflammatory response.

Conclusion: Knockdown of miR-770-5p suppressed podocyte apoptosis and inflammatory response by targeting TIMP3 in HG-treated podocytes, indicating that miR-770-5p may be a potential therapeutic target for DN therapy.

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<![CDATA[Comprehensive analysis of PPARγ agonist activities of stereo-, regio-, and enantio-isomers of hydroxyoctadecadienoic acids]]> https://www.researchpad.co/article/Ncba0b326-176f-4db2-bf87-2a3eba460f56 Hydroxyoctadecadienoic acids (HODEs) are produced by oxidation and reduction of linoleates. There are several regio- and stereo-isomers of HODE, and their concentrations in vivo are higher than those of other lipids. Although conformational isomers may have different biological activities, comparative analysis of intracellular function of HODE isomers has not yet been performed. We evaluated the transcriptional activity of peroxisome proliferator-activated receptor γ (PPARγ), a therapeutic target for diabetes, and analyzed PPARγ agonist activity of HODE isomers. The lowest scores for docking poses of 12 types of HODE isomers (9-, 10-, 12-, and 13-HODEs) were almost similar in docking simulation of HODEs into PPARγ ligand-binding domain (LBD). Direct binding of HODE isomers to PPARγ LBD was determined by water-ligand observed via gradient spectroscopy (WaterLOGSY) NMR experiments. In contrast, there were differences in PPARγ agonist activities among 9- and 13-HODE stereo-isomers and 12- and 13-HODE enantio-isomers in a dual-luciferase reporter assay. Interestingly, the activity of 9-HODEs was less than that of other regio-isomers, and 9-(E,E)-HODE tended to decrease PPARγ-target gene expression during the maturation of 3T3-L1 cells. In addition, 10- and 12-(Z,E)-HODEs, which we previously proposed as biomarkers for early-stage diabetes, exerted PPARγ agonist activity. These results indicate that all HODE isomers have PPARγ-binding affinity; however, they have different PPARγ agonist activity. Our findings may help to understand the biological function of lipid peroxidation products.

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<![CDATA[The natural drug DIAVIT is protective in a type II mouse model of diabetic nephropathy]]> https://www.researchpad.co/article/5c92b34ad5eed0c4843a3d15

There is evidence to suggest that abnormal angiogenesis, inflammation, and fibrosis drive diabetic nephropathy (DN). However, there is no specific treatment to counteract these processes. We aimed to determine whether DIAVIT, a natural Vaccinium myrtillus (blueberry) and Hippophae Rhamnoides (sea buckthorn) extract, is protective in a model of type II DN. Diabetic db/db mice were administered DIAVIT in their drinking water for 14 weeks. We assessed the functional, structural, and ultra-structural phenotype of three experimental groups (lean+vehicle, db/db+vehicle, db/db+DIAVIT). We also investigated the angiogenic and fibrotic pathways involved in the mechanism of action of DIAVIT. Diabetic db/db mice developed hyperglycaemia, albuminuria, and an increased glomerular water permeability; the latter two were prevented by DIAVIT. db/db mice developed fibrotic glomeruli, endothelial insult, and glomerular ultra-structural changes, which were not present in DIAVIT-treated mice. Vascular endothelial growth factor A (VEGF-A) splicing was altered in the db/db kidney cortex, increasing the pro-angiogenic VEGF-A165 relative to the anti-angiogenic VEGF-A165b. This was partially prevented with DIAVIT treatment. Delphinidin, an anthocyanin abundant in DIAVIT, increased the VEGF-A165b expression relative to total VEGF-A165 in cultured podocytes through phosphorylation of the splice factor SRSF6. DIAVIT, in particular delphinidin, alters VEGF-A splicing in type II DN, rescuing the DN phenotype. This study highlights the therapeutic potential of natural drugs in DN through the manipulation of gene splicing and expression.

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<![CDATA[Blood co-expression modules identify potential modifier genes of diabetes and lung function in cystic fibrosis]]> https://www.researchpad.co/article/N07a3560c-fa96-4eb5-821e-9292b7a2bef0

Cystic fibrosis (CF) is a rare genetic disease that affects the respiratory and digestive systems. Lung disease is variable among CF patients and associated with the development of comorbidities and chronic infections. The rate of lung function deterioration depends not only on the type of mutations in CFTR, the disease-causing gene, but also on modifier genes. In the present study, we aimed to identify genes and pathways that (i) contribute to the pathogenesis of cystic fibrosis and (ii) modulate the associated comorbidities. We profiled blood samples in CF patients and healthy controls and analyzed RNA-seq data with Weighted Gene Correlation Network Analysis (WGCNA). Interestingly, lung function, body mass index, the presence of diabetes, and chronic P. aeruginosa infections correlated with four modules of co-expressed genes. Detailed inspection of networks and hub genes pointed to cell adhesion, leukocyte trafficking and production of reactive oxygen species as central mechanisms in lung function decline and cystic fibrosis-related diabetes. Of note, we showed that blood is an informative surrogate tissue to study the contribution of inflammation to lung disease and diabetes in CF patients. Finally, we provided evidence that WGCNA is useful to analyze–omic datasets in rare genetic diseases as patient cohorts are inevitably small.

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<![CDATA[Variation in plasma 25-hydroxyvitamin D2 and D3 in normal pregnancy with gestational age, sampling season, and complications: A longitudinal cohort study]]> https://www.researchpad.co/article/Ndf1a2733-e0b1-4fc7-90ad-b2bfa4368f5f

Introduction

Low levels of vitamin D in pregnancy have been associated with the risk of a variety of pregnancy outcomes. Few studies have investigated vitamin D concentrations throughout pregnancy in healthy women, and most guidelines recommend high vitamin D levels. In the present study, we investigated 25-hydroxyvitamin D concentrations in healthy Caucasian Danish women in relation to season, gestational age and possible vitamin D-linked complications.

Materials and methods

Eight hundred and one healthy Caucasian Danish women with an expected normal pregnancy were recruited among 2147 women attending first trimester screening. Seven blood samplings were planned throughout the pregnancy and delivery period. The 25-hydroxyvitamin D2 (25(OH)D2) and 25-hydroxyvitamin D3 (25(OH)D3) concentrations were measured by LC-MS/MS and total 25-hydroxyvitamin D (25(OH)D) were calculated.

Results

A total of 3304 samples from 694 women were available for 25(OH)D measurements. The mean (25th-75th percentiles) concentrations of 25(OH)D, 25(OH)D3, and 25(OH)D2 were 54.6 (38.8–68.6) nmol/L, 52.2 (36.4–66.4) nmol/L, and 2.4 (2.2–2.2) nmol/L, respectively. Season was the strongest predictor of 25(OH)D concentration, with the lowest values observed in winter and spring, where only 42% and 41% of samples, respectively, were above 50 nmol/L. Nearly all women had values below the suggested optimal level of 75 nmol/L, independent of season. 25(OH)D peaked at gestational weeks 21–34. Plasma 25(OH)D2 levels were low in all seasons. Women with complications during pregnancy had higher 25(OH)D (estimated difference 9.8 nmol/L, standard error 2.7, p<0.001) than did women without complications, and women giving birth vaginally had lower 25(OH)D than did those delivering via elective (10.0 nmol/L, standard error 2.1, p<0.001) or emergency cesarean section (6.8 nmol/L, standard error 2.2, p<0.001).

Conclusion

The 25(OH)D concentrations vary with both season and gestational age. Healthy women had lower 25(OH)D concentrations than recommended, without an association with an increased risk of pregnancy complications. Guidelines for vitamin D in pregnancy may require revision.

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<![CDATA[Effects of emodin on inflammatory bowel disease-related osteoporosis]]> https://www.researchpad.co/article/Ndf5dd2c6-1bd2-42f9-92d8-2a5c6fe403f5

Abstract

Inflammatory bowel diseases (IBD) are related to bone loss. Emodin can influence the activity and differentiation of osteoblasts and osteoclasts. However, few studies have shown the effects of emodin on IBD-induced bone damage. The aim of the present study was to investigate the role of emodin in IBD-induced osteoporosis in an animal model. An IBD model in Sprague Dawley male rats was established by administering 2.5% dextran sulfate sodium (DSS) in the drinking water. Emodin was administered orally (30 mg/kg body weight) every other day starting in the third week for 9 weeks. Blood, colon and bone samples were obtained for biomarker assays and histological analysis. Bone biomechanical properties, microCT, metabolic biomarkers and bone histological changes were analyzed. The bone mass was significantly decreased, and the bone biomechanical properties and bone microstructure parameters of IBD rats were significantly worse than those of control rats (P<0.05). Tartrate resistant acid phosphatase staining also showed that the number of osteoclasts in bone in IBD rats were larger than that in bone in control rats. Emodin intervention abolished the changes in bone microstructure and biomechanical properties (P<0.05) induced by IBD. Osteoclast formation and serum C-terminal cross-linked peptide (CTX) and tumor necrosis factor α (TNF-α) were also inhibited by emodin (P<0.05). Emodin significantly abolished IBD-enhanced Traf6, NFATC1 and c-fos expression. Our data demonstrated that emodin suppresses IBD-induced osteoporosis by inhibiting osteoclast formation.

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<![CDATA[Agreement between cardiovascular disease risk assessment tools: An application to the United Arab Emirates population]]> https://www.researchpad.co/article/N9ca1ffb4-d1e9-4710-8aa8-6eec943148b3

Introduction

Evidence regarding the performance of cardiovascular disease (CVD) risk assessment tools is limited in the United Arab Emirates (UAE). Therefore, we assessed the agreement between various externally validated CVD risk assessment tools in the UAE.

Methods

A secondary analysis of the Abu Dhabi Screening Program for Cardiovascular Risk Markers (AD-SALAMA) data, a large population-based cross-sectional survey conducted in Abu Dhabi, UAE during the period 2009 until 2015, was performed in July 2019. The analysis included 2,621 participants without type 2 Diabetes and without history of cardiovascular diseases. The CVD risk assessment tools included in the analysis were the World Health Organization for Middle East and North Africa Region (WHO-MENA), the systematic coronary risk evaluation for high risk countries (SCORE-H), the pooled cohort risk equations for white (PCRE-W) and African Americans (PCRE-AA), the national cholesterol education program Framingham risk score (FRAM-ATP), and the laboratory Framingham risk score (FRAM-LAB).

Results

The overall concordance coefficient was 0.50. The agreement between SCORE-H and PCRE-W, PCRE-AA, FRAM-LAB, FRAM-ATP and WHO-MENA, were 0.47, 0.39, 0.0.25, 0.42 and 0.18, respectively. PCRE-AA classified the highest proportion of participants into high-risk category of CVD (16.4%), followed by PCRE-W (13.6%), FRAM-LAB (6.9%), SCORE-H (4.5%), FRAM-ATP (2.7%), and WHO-MENA (0.4%).

Conclusions

We found a poor agreement between various externally validated CVD risk assessment tools when applied to a large data collected in the UAE. This poses a challenge to choose any of these tools for clinical decision-making regarding the primary prevention of CVD in the country.

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<![CDATA[Astragalus polysaccharide attenuates metabolic memory-triggered ER stress and apoptosis via regulation of miR-204/SIRT1 axis in retinal pigment epithelial cells]]> https://www.researchpad.co/article/Nb971e286-5132-48e1-a2b1-bf3c7361ba61

Abstract

Background:Metabolic memory’ of early hyperglycaemic environment has been frequently suggested in the progression of diabetic retinopathy (DR). Retinal pigment epithelial (RPE) cells are crucial targets for DR initiation following hyperglycaemia. Astragalus polysaccharides (APS) has been long used as a traditional Chinese medicine in treating diabetes. In the present study, the preventive effects and mechanisms of APS on metabolic memory-induced RPE cell death were investigated.

Methods: The expressions of miR-204 and SIRT1 were determined by reverse transcription quantitative PCR (RT-qPCR). Dual luciferase assay was applied to detect the potential targeting effects of miR-204 on SIRT1. SIRT1, ER stress and apoptosis related proteins were monitored using Western blotting. Apoptosis was assessed by TUNEL assay and Annexin V/PI staining followed by flow cytometry analysis. MiR-204 mimics and shSIRT1 were applied for miR-204 overexpression and SIRT1 knockdown, respectively.

Results: High glucose exposure induced metabolic memory, which was accompanied with sustained dysregulation of miR-204/SIRT1 axis, high level of ER stress and activation of apoptotic pathway even after replacement with normal glucose. Pre-treatment with APS concentration-dependently reversed miR-204 expression, leading to disinhibition of SIRT1 and alleviation of ER stress-induced apoptosis indicated by decreased levels of p-PERK, p-IRE-1, cleaved-ATF6, Bax, cleaved caspase-12, -9, -3, and increased levels of Bcl-2 and unleaved PARP. The effects of APS on RPE cells were reversed by either miR-204 overexpression or SIRT1 knockdown.

Conclusions: We concluded that APS inhibited ER stress and subsequent apoptosis via regulating miR-204/SIRT1 axis in metabolic memory model of RPE cells.

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<![CDATA[RCAN1.4 mediates high glucose-induced matrix production by stimulating mitochondrial fission in mesangial cells]]> https://www.researchpad.co/article/Nf1969b5b-fdb5-4108-bdef-6f37c3b5d961

Abstract

High glucose (HG)-induced mitochondrial dynamic changes and oxidative damage are closely related to the development and progression of diabetic kidney disease (DKD). Recent studies suggest that regulators of calcineurin 1 (RCAN1) is involved in the regulation of mitochondrial function in different cell types, so we investigate the role of RCAN1 in mitochondrial dynamics under HG ambience in rat glomerular mesangial cells (MCs). MCs subjected to HG exhibited an isoform-specific up-regulation of RCAN1.4 at both mRNA and protein levels. RCAN1.4 overexpression induced translocation of Dynamin related protein 1 (Drp1) to mitochondria, mitochondrial fragmentation and depolarization, accompanied by increased matrix production under normal glucose and HG ambience. In contrast, decreasing the expression of RCAN1.4 by siRNA inhibited HG-induced mitochondrial fragmentation and matrix protein up-regulation. Moreover, both mitochondrial fission inhibitor Mdivi-1 and Drp1 shRNA prevented RCAN1.4-induced fibronectin up-regulation, suggesting that RCAN1.4-induced matrix production is dependent on its modulation of mitochondrial fission. Although HG-induced RCAN1.4 up-regulation was achieved by activating calcineurin, RCAN1.4-mediated mitochondrial fragmentation and matrix production is independent of calcineurin activity. These results provide the first evidence for the HG-induced RCAN1.4 up-regulation involving increased mitochondrial fragmentation, leading to matrix protein up-regulation.

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<![CDATA[Incidence of statin use in older adults with and without cardiovascular disease and diabetes mellitus, January 2008- March 2018]]> https://www.researchpad.co/article/N40ec07ea-30b4-4753-a09f-b8fe9ef6ec46

Background

Data from randomized controlled trials and observational studies on older adults who take statins for primary prevention of atherosclerotic cardiovascular disease are limited. To determine the incidence of statin use in older adults with and without cardiovascular disease (CVD) and/or diabetes (DM), we conducted a descriptive observational study.

Methods

The cohort consisted of health plan members in the NIH Collaboratory Distributed Research Network aged >75 years who had continuous drug and medical benefits for ≥183 days during the study period, January 1, 2008- March 31, 2018. We defined DM and CVD using diagnosis codes, and identified statins using dispensing data. Statin use was considered incident if a member had no evidence of statin exposure in the claims during the previous 183 days, and the use was considered long-term if statins were supplied for ≥180 days. Incidence rates were reported among members with and without CVD and/or diabetes, and stratified by year, sex, and age group.

Results

Among 757,569 eligible members, 109,306 older adults initiated statins and 54,624 became long-term users. Health plan members with CVD had the highest incidence of statin use (143.9 initiators per 1,000 member-years for CVD & DM; 114.5 initiators per 1,000 member-years for CVD & No DM). Among health plan members without CVD, those with DM had rates of statin use that were over two times higher than members without DM (76.1 versus 34.5 initiators per 1,000 member-years, respectively). Statin initiation remained steady throughout 2008–2016, was slightly higher in males, and declined with increasing age.

Conclusion

Incidence of statin use varied by CVD and DM comorbidity, and was lowest among those without CVD. These results highlight the potential clinical equipoise to conduct large pragmatic clinical trials to generate evidence that could be used to inform future blood cholesterol guidelines.

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<![CDATA[Exploring the geography of serious mental illness and type 2 diabetes comorbidity in Illawarra—Shoalhaven, Australia (2010 -2017)]]> https://www.researchpad.co/article/N645ccd00-2b7d-4514-8bd1-1e99a3f678df

Objectives

The primary aim of this study was to describe the geography of serious mental illness (SMI)–type 2 diabetes comorbidity (T2D) in the Illawarra-Shoalhaven region of NSW, Australia. The Secondary objective was to determine the geographic concordance if any, between the comorbidity and the single diagnosis of SMI and diabetes.

Methods

Spatial analytical techniques were applied to clinical data to explore the above objectives. The geographic variation in comorbidity was determined by Moran’s I at the global level and the local clusters of significance were determined by Local Moran’s I and spatial scan statistic. Choropleth hotspot maps and spatial scan statistics were generated to assess the geographic convergence of SMI, diabetes and their comorbidity. Additionally, we used bivariate LISA (Local Indicators of Spatial Association) and multivariate spatial scan to identify coincident areas with higher rates of both SMI and T2D.

Results

The study identified significant geographic variation in the distribution of SMI–T2D comorbidity in Illawarra Shoalhaven. Consistently higher burden of comorbidity was observed in some urban suburbs surrounding the major metropolitan city. Comparison of comorbidity hotspots with the hotspots of single diagnosis SMI and T2D further revealed a geographic concordance of high-risk areas again in the urban areas outside the major metropolitan city.

Conclusion

The identified comorbidity hotspots in our study may serve as a basis for future prioritisation and targeted interventions. Further investigation is required to determine whether contextual environmental factors, such as neighbourhood socioeconomic disadvantage, may be explanatory.

Implications for public health

Ours is the first study to explore the geographic variations in the distribution of SMI and T2D comorbidity. Findings highlight the importance of considering the role of neighbourhood environments in influencing the T2D risk in people with SMI.

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