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BMJ Open Diabetes Research & Care Jun 2024We previously reported predictors of mortality in 1786 adults with diabetes or stress hyperglycemia (glucose>180 mg/dL twice in 24 hours) admitted with COVID-19 from...
INTRODUCTION
We previously reported predictors of mortality in 1786 adults with diabetes or stress hyperglycemia (glucose>180 mg/dL twice in 24 hours) admitted with COVID-19 from March 2020 to February 2021 to five university hospitals. Here, we examine predictors of readmission.
RESEARCH DESIGN AND METHODS
Data were collected locally through retrospective reviews of electronic medical records from 1786 adults with diabetes or stress hyperglycemia who had a hemoglobin A1c (HbA1c) test on initial admission with COVID-19 infection or within 3 months prior to initial admission. Data were entered into a Research Electronic Data Capture (REDCap) web-based repository, and de-identified. Descriptive data are shown as mean±SD, per cent (%) or median (IQR). Student's t-test was used for comparing continuous variables with normal distribution and Mann-Whitney U test was used for data not normally distributed. X test was used for categorical variable.
RESULTS
Of 1502 patients who were alive after initial hospitalization, 19.4% were readmitted; 90.3% within 30 days (median (IQR) 4 (0-14) days). Older age, lower estimated glomerular filtration rate (eGFR), comorbidities, intensive care unit (ICU) admission, mechanical ventilation, diabetic ketoacidosis (DKA), and longer length of stay (LOS) during the initial hospitalization were associated with readmission. Higher HbA1c, glycemic gap, or body mass index (BMI) were not associated with readmission. Mortality during readmission was 8.0% (n=23). Those who died were older than those who survived (74.9±9.5 vs 65.2±14.4 years, p=0.002) and more likely had DKA during the first hospitalization (p<0.001). Shorter LOS during the initial admission was associated with ICU stay during readmission, suggesting that a subset of patients may have been initially discharged prematurely.
CONCLUSIONS
Understanding predictors of readmission after initial hospitalization for COVID-19, including older age, lower eGFR, comorbidities, ICU admission, mechanical ventilation, statin use and DKA but not HbA1c, glycemic gap or BMI, can help guide treatment approaches and future research in adults with diabetes.
Topics: Humans; COVID-19; Patient Readmission; Male; Female; Hyperglycemia; Middle Aged; Retrospective Studies; Aged; Glycated Hemoglobin; SARS-CoV-2; Diabetes Mellitus; Hospitalization; Adult; Risk Factors; Aged, 80 and over; Blood Glucose
PubMed: 38937276
DOI: 10.1136/bmjdrc-2024-004167 -
BMJ Open Diabetes Research & Care Jun 2024Type 2 diabetes mellitus (T2DM) is associated with dysbiosis in the gut microbiota (MB). Individually, each medication appears to partially correct this. However, there...
INTRODUCTION
Type 2 diabetes mellitus (T2DM) is associated with dysbiosis in the gut microbiota (MB). Individually, each medication appears to partially correct this. However, there are no studies on the response of the MB to changes in A1c. Therefore, we investigated the MB's response to intensive glycemic control.
RESEARCH DESIGN AND METHODS
We studied two groups of patients with uncontrolled T2DM, one group with an A1c <9% (18 patients-G1) and another group with an A1c >9% (13 patients-G2), aiming for at least a 1% reduction in A1c. We collected A1c and fecal samples at baseline, 6, and 12 months. G1 achieved an average A1c reduction of 1.1%, while G2 a reduction of 3.13%.
RESULTS
G1's microbiota saw a decrease in Erysipelotrichaceae_UCG_003 and in Mollicutes order (both linked to metabolic syndrome and associated comorbidities). G2, despite having a more significant reduction in A1c, experienced an increase in the proinflammatory bacteria and , and only one beneficial genus, , increased, producer of butyrate.
CONCLUSION
Despite a notable A1c outcome, G2 could not restore its MB. This seeming resistance to change, leading to a persistent inflammation component found in G2, might be part of the "metabolic memory" in T2DM.
Topics: Humans; Dysbiosis; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Male; Female; Middle Aged; Glycated Hemoglobin; Aged; Feces; Blood Glucose; Follow-Up Studies; Hypoglycemic Agents; Glycemic Control; Biomarkers; Prognosis
PubMed: 38937275
DOI: 10.1136/bmjdrc-2023-003964 -
Molecular Metabolism Jun 2024The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise with the increasing obesity epidemic. Rezdiffra as an activator of a...
OBJECTIVE
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise with the increasing obesity epidemic. Rezdiffra as an activator of a thyroid hormone receptor-beta is the only Food and Drug Administration approved therapy. As such, there is a critical need to improve our understanding of gene expression regulation and signaling transduction in MASLD to develop new therapies. Matrin-3 is a DNA- and RNA-binding protein involved in the pathogenesis of human diseases. Here we examined its previously uncharacterized role in limiting hepatic steatosis and stress response via the constitutive androstane receptor (CAR).
METHODS
Matrin-3 floxed and liver-specific knockout mice were fed either a chow diet or 60 kcal% high-fat diet (HFD) for up to 16 weeks. The mice were euthanized for different analysis including liver histology, lipid levels, and gene expression. Bulk RNA-seq, bulk ATAC-seq, and single-nucleus Multiome were used to examine changes of transcriptome and chromatin accessibility in the liver. Integrative bioinformatics analysis of our data and publicly available datasets and different biochemical assays were performed to identify underlying the molecular mechanisms mediating matrin-3's effects. Liver-tropic adeno-associated virus was used to restore the expression of CAR for lipid, acute phase genes, and histological analysis.
RESULTS
Matrin-3 expression is induced in the steatotic livers of mice. Liver-specific matrin-3 deletion exacerbated HFD-induced steatosis, acute phase response, and inflammation in the liver of female mice. The transcriptome and chromatin accessibility were re-programmed in the liver of these mice with signatures indicating that CAR signaling is dysregulated. Mechanistically, matrin-3 interacts with CAR mRNA, and matrin-3 deficiency promotes CAR mRNA degradation. Consequently, matrin-3 deletion impaired CAR signaling by reducing CAR expression. Matrin-3 levels positively correlate with CAR expression in human livers. Ces2a and Il1r1 were identified as new target genes of CAR. Interestingly, we found that CAR discords with the expression of its target genes including Cyp2b10 and Ces2a in response to HFD, indicating CAR signaling is dysregulated by HFD despite increased CAR expression. Dysregulated CAR signaling upon matrin-3 deficiency reduced Ces2a and de-repressed Il1r1 expression. CAR restoration partially abrogated the dysregulated gene expression, exacerbated hepatic steatosis, acute phase response, and inflammation in liver-specific matrin-3 knockout mice fed a HFD.
CONCLUSIONS
Our findings demonstrate that matrin-3 is a key upstream regulator maintaining CAR signaling upon metabolic stress, and the matrin-3-CAR axis limits hepatic steatosis and stress response signaling that may give insights for therapeutic intervention.
PubMed: 38936659
DOI: 10.1016/j.molmet.2024.101977 -
PloS One 2024
Topics: Animals; Frontotemporal Dementia; Mice; Humans; tau Proteins; Mutation; Genotype; Cell Line; Central Nervous System
PubMed: 38935762
DOI: 10.1371/journal.pone.0305843 -
PloS One 2024Understanding patient satisfaction is key to advancing pharmacy services and improving health outcomes. There is a lack of a translated and psychometrically validated...
Translation, cultural adaptation and validation of Patient Satisfaction with Pharmacist Services Questionnaire (PSPSQ) 2.0 into the Arabic language among people with diabetes.
BACKGROUND
Understanding patient satisfaction is key to advancing pharmacy services and improving health outcomes. There is a lack of a translated and psychometrically validated tool in the Arabic language to measure patient satisfaction with pharmacy services.
OBJECTIVE
To translate the English version of the PSPSQ 2.0 into Arabic language, culturally adapt, and verify its reliability and validity.
SETTING
A community pharmacy in Riyadh, Saudi Arabia.
METHOD
A cross-sectional study was conducted between April 2021 and June 2022 among patients with diabetes attending a community pharmacy. The International Society for Pharmacoeconomics and Outcomes Research good practice guidelines for linguistic translation and cultural adaptation were used to translate and culturally adapt the English version of PSPSQ 2.0 into Arabic. The Arabic version of PSPSQ 2.0 was subjected to factor analysis using principal component analysis with varimax rotation to evaluate its validity and Cronbach's alpha was used to assess the reliability of PSPSQ 2.0.
RESULTS
A total of 129 (68.2% male, and mean age 50 (SD: 11.9) years) patients with diabetes participated in the study. The analysis was undertaken for the items in each of the three domains of PSPSQ 2.0: quality of care, interprofessional relationship and overall care. Exploratory factor analysis revealed validity of 92.7%, 80.5% and 96.2%, respectively. The Arabic version of PSPSQ 2.0 had high internal consistency with Cronbach's alpha scores 0.99, 0.95 and 0.98 for the three measured domains, respectively. The sample adequacy was 0.924.
CONCLUSION
The PSPSQ 2.0 was successfully translated and culturally adapted into the Arabic language and had acceptable validity and reliability to measure patient satisfaction with services provided by pharmacists in community pharmacies.
Topics: Humans; Male; Female; Patient Satisfaction; Middle Aged; Surveys and Questionnaires; Diabetes Mellitus; Saudi Arabia; Language; Adult; Cross-Sectional Studies; Translations; Reproducibility of Results; Psychometrics; Pharmacists; Translating; Community Pharmacy Services
PubMed: 38935668
DOI: 10.1371/journal.pone.0298848 -
PloS One 2024Chronic liver diseases are caused by hepatic viral infection, chemicals, and metabolic stress. The protein Grb2-associated binder 1 (Gab1) binds to various growth factor...
Chronic liver diseases are caused by hepatic viral infection, chemicals, and metabolic stress. The protein Grb2-associated binder 1 (Gab1) binds to various growth factor receptors, and triggers cell differentiation/survival signaling pathways. To identify signaling molecules involved in the progression of liver diseases, we performed reverse-phase protein microarray (RPMA)-based screening of hepatocytes isolated from humanized mice after acute HCV infection. Acute viral infection in humanized liver mice significantly decreased the level of hepatocyte p-Gab1. Moreover, hepatoma cells upon HCV infection decreased Gab1 mRNA at later times of infection (D3 to D5) and p-Gab1 level was inversely related to the production of TGF-β. In contrast, the level of p-Gab1 was increased in CCL4-induced fibrotic liver. Hepatoma cells showed elevation of p-Gab1, along with an increase in STAT3 and ERK activation, upon treatment with HGF (ligand of HGF receptor/c-Met) and CCL4. In Gab1 knockdown hepatoma cells, cell proliferative signaling activity was reduced but the level of activated caspase-3 was increased. These findings suggest that hepatocyte Gab1 expression may play a role in promoting liver fibrosis progression by triggering ERK activation and inhibiting apoptosis. It implies that the Gab1-mediated signaling pathway would be a promising therapeutic target to treat chronic liver diseases.
Topics: Animals; Hepatocytes; Liver Cirrhosis; Adaptor Proteins, Signal Transducing; Apoptosis; Signal Transduction; Cell Proliferation; Humans; Mice; Proto-Oncogene Proteins c-met; Hepatocyte Growth Factor; Cell Line, Tumor; Hepatitis C
PubMed: 38935609
DOI: 10.1371/journal.pone.0306345 -
PloS One 2024Diabetes is a chronic disease associated with the potential for blindness, kidney failure, heart attacks, strokes, and lower limb amputations. The global prevalence of...
BACKGROUND
Diabetes is a chronic disease associated with the potential for blindness, kidney failure, heart attacks, strokes, and lower limb amputations. The global prevalence of diabetes is rising, particularly in the sub-Saharan African (SSA) region, where accessing treatment and antidiabetic drugs is complex, leading to challenges in managing the condition. Intentional and structured therapeutic education has demonstrated its ability to enhance health outcomes in diabetes patients. Given the numerous healthcare deficiencies in sub-Saharan Africa, the authors have reevaluated the role of therapeutic patient education (TPE) in this context.
METHODS
This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We queried four databases between March 14 and June 30, 2023 and conducted Cochrane's Risk of Bias analysis on the included studies. Subsequently, a qualitative synthesis of the results was performed.
RESULTS
The final analysis included thirteen studies. Seven of these, which assessed glycemic control, reported statistically significant results. Additionally, other clinical parameters such as body mass index (BMI), blood pressure, and lipid levels also exhibited some significant improvements. Knowledge substantially increased following the intervention, while attitude, self-care practices, and medication adherence showed no significant improvements. Nurse-led and peer-led intervention programs produced positive outcomes, whereas technology-based intervention methods did not yield favorable results.
CONCLUSION
TPE programs in sub-Saharan Africa have a significant impact on both clinical and non-clinical outcomes in diabetes patients. However, the sustainability of these outcomes remains uncertain. Further research is needed to assess the long-term effects of TPE on diabetes patients.
Topics: Humans; Africa South of the Sahara; Patient Education as Topic; Diabetes Mellitus; Medication Adherence; Self Care; Health Knowledge, Attitudes, Practice
PubMed: 38935594
DOI: 10.1371/journal.pone.0299526 -
Neurologia I Neurochirurgia Polska Jun 2024Lambert-Eaton myasthenic syndrome (LEMS) is an ultrarare neuromuscular disease with a triad of symptoms: muscle paresis, dysautonomy, and areflexia. Amifampridine is the...
INTRODUCTION
Lambert-Eaton myasthenic syndrome (LEMS) is an ultrarare neuromuscular disease with a triad of symptoms: muscle paresis, dysautonomy, and areflexia. Amifampridine is the symptomatic treatment of LEMS.
AIM OF STUDY
To assess the effectiveness and safety of treatment in the real world.
MATERIAL AND METHODS
14 patients with non-neoplastic LEMS treated with amifampridine were enrolled in the study (female 42.9%, mean age 48.8 ± 11.4 years). The patients were assessed using the Quantitative Myasthenia Gravis (QMG) scale, QMG limb domain (LD) score, spirometry, Hand Grip Strength (GRIP) test, and repetitive nerve stimulation study (RNS) at baseline and at the end of follow-up. Diagnostic delay since first symptoms was from seven months up to 22 years. Treatment delay ranged from one to 26 years. The patients were treated and reevaluated after 21.1 ± 12.0 weeks (range 13-48).
RESULTS
All of the patients improved in QMG score. Mean improvement was 5.1 ± 2.0 (range 1-8) points (p < 0.001) and this showed no correlation with the duration of the disease before treatment (p = 0.477). 85.7% of patients (N = 12) improved ≥ 3 points (clinically meaningful) in QMG. 78.6% of the patients improved in QMG LD (mean 2.2 ± 1.6 points (p < 0.001)). Also, forced vital capacity (FVC) improved after treatment (p = 0.031). Mean improvement in GRIP test was 7.0 ± 7.1 kg in the right hand and 5.2 ± 7.5 kg in the left hand (p < 0.001). In RNS before treatment, facilitation ( > 100%) was observed in 78.6% (N = 11) of patients, and was higher before treatment (p < 0.001). Compound muscle action potential (CMAP) amplitude was higher after treatment (p < 0.001). Mean increase of CMAP amplitude was 2.1 ± 1.6 times. In 64.3% (N = 9) of patients lowering of corticosteroid dose was achieved.
CONCLUSIONS
Amifampridine is an effective treatment in non-neoplastic LEMS patients, regardless of disease duration. The treatment is well-tolerated and allows to reduce dose of corticosteroids in the majority of patients.
PubMed: 38935421
DOI: 10.5603/pjnns.99335 -
JMIR Research Protocols Jun 2024Individuals at high risk for type 2 diabetes are also at an increased risk for developing cardiovascular disease (CVD). Although there are separate trials examining the...
Effects of Lifestyle Interventions on Cardiovascular Disease Risk and Risk Factors Among Individuals at High Risk for Type 2 Diabetes: Protocol for a Systematic Review and Meta-Analysis of Randomized Controlled Trials.
BACKGROUND
Individuals at high risk for type 2 diabetes are also at an increased risk for developing cardiovascular disease (CVD). Although there are separate trials examining the effects of lifestyle interventions on absolute CVD risk among people at high risk for type 2 diabetes, a comprehensive evidence synthesis of these trials is lacking.
OBJECTIVE
We will systematically synthesize the evidence on the effects of lifestyle interventions in reducing absolute CVD risk and CVD risk factors among people at high risk for type 2 diabetes.
METHODS
We adhered to the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) statement in reporting the details of this protocol. Randomized controlled trials of diabetes prevention that examined the effects of lifestyle interventions for at least 6 months on absolute CVD risk and CVD risk factors among individuals at high risk for type 2 diabetes will be eligible. We will systematically search the MEDLINE, Embase, PsycINFO, CENTRAL, and Scopus databases and ClinicalTrials.gov using a mix of Medical Subject Headings and text words. Two authors will independently screen the abstract and title of the articles retrieved from the search, followed by full-text reviews using the inclusion and exclusion criteria and data extraction from the eligible studies. Article screening and data extraction will be performed in the Covidence software. The primary outcome will be the changes in absolute 10-year CVD risk, as estimated by risk prediction models. The secondary outcomes are the changes in CVD risk factors, including behavioral, clinical, biochemical, and psychosocial risk factors, and incidence of type 2 diabetes.
RESULTS
An initial database search was conducted in July 2023. After screening 1935 articles identified through the database search, 42 articles were considered eligible for inclusion. It is anticipated that the study findings will be submitted for publication in a peer-reviewed journal by the end of 2024.
CONCLUSIONS
This study will provide up-to-date, systematically synthesized evidence on the effects of lifestyle interventions on absolute CVD risk and CVD risk factors among individuals at high risk for type 2 diabetes.
TRIAL REGISTRATION
PROSPERO CRD42023429869; https://tinyurl.com/59ajy7rw.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/53517.
Topics: Humans; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Systematic Reviews as Topic; Randomized Controlled Trials as Topic; Meta-Analysis as Topic; Risk Factors; Life Style; Risk Reduction Behavior; Female; Male; Heart Disease Risk Factors
PubMed: 38935416
DOI: 10.2196/53517 -
Journal of the American Heart... Jun 2024The association between soy isoflavones intake and cardiometabolic health remains inconclusive. We investigated the associations of urinary biomarkers of isoflavones...
BACKGROUND
The association between soy isoflavones intake and cardiometabolic health remains inconclusive. We investigated the associations of urinary biomarkers of isoflavones including daidzein, glycitein, genistein, equol (a gut microbial metabolite of daidzein), and equol-predicting microbial species with cardiometabolic risk markers.
METHODS AND RESULTS
In a 1-year study of 305 Chinese community-dwelling adults aged ≥18 years, urinary isoflavones, fecal microbiota, blood pressure, blood glucose and lipids, and anthropometric data were measured twice, 1 year apart. Brachial-ankle pulse wave velocity was also measured after 1 year. A linear mixed-effects model was used to analyze repeated measurements. Logistic regression was used to calculate the adjusted odds ratio (aOR) and 95% CI for the associations for arterial stiffness. Each 1 μg/g creatinine increase in urinary equol concentrations was associated with 1.47%, 0.96%, and 3.32% decrease in triglycerides, plasma atherogenic index, and metabolic syndrome score, respectively (all <0.05), and 0.61% increase in high-density lipoprotein cholesterol (=0.025). Urinary equol was also associated with lower risk of arterial stiffness (aOR, 0.28 [95% CI, 0.09-0.90]; =0.036). We identified 21 bacterial genera whose relative abundance was positively associated with urinary equol (false discovery rate-corrected <0.05) and constructed a microbial species score to reflect the overall equol-predicting capacity. This score (per 1-point increase) was inversely associated with triglycerides (percentage difference=-1.48%), plasma atherogenic index (percentage difference=-0.85%), and the risk of arterial stiffness (aOR, 0.27 [95% CI, 0.08-0.88]; all <0.05).
CONCLUSIONS
Our findings suggest that urinary equol and equol-predicting microbial species may improve cardiometabolic risk parameters in Chinese adults.
PubMed: 38934874
DOI: 10.1161/JAHA.123.034126