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Stem Cell Research & Therapy Jun 2024Diabetes mellitus, a significant global public health challenge, severely impacts human health worldwide. The organoid, an innovative in vitro three-dimensional (3D)... (Review)
Review
Diabetes mellitus, a significant global public health challenge, severely impacts human health worldwide. The organoid, an innovative in vitro three-dimensional (3D) culture model, closely mimics tissues or organs in vivo. Insulin-secreting islet organoid, derived from stem cells induced in vitro with 3D structures, has emerged as a potential alternative for islet transplantation and as a possible disease model that mirrors the human body's in vivo environment, eliminating species difference. This technology has gained considerable attention for its potential in diabetes treatment. Despite advances, the process of stem cell differentiation into islet organoid and its cultivation demonstrates deficiencies, prompting ongoing efforts to develop more efficient differentiation protocols and 3D biomimetic materials. At present, the constructed islet organoid exhibit limitations in their composition, structure, and functionality when compared to natural islets. Consequently, further research is imperative to achieve a multi-tissue system composition and improved insulin secretion functionality in islet organoid, while addressing transplantation-related safety concerns, such as tumorigenicity, immune rejection, infection, and thrombosis. This review delves into the methodologies and strategies for constructing the islet organoid, its application in diabetes treatment, and the pivotal scientific challenges within organoid research, offering fresh perspectives for a deeper understanding of diabetes pathogenesis and the development of therapeutic interventions.
Topics: Humans; Organoids; Islets of Langerhans; Animals; Islets of Langerhans Transplantation; Diabetes Mellitus; Cell Differentiation
PubMed: 38937834
DOI: 10.1186/s13287-024-03780-7 -
BMC Public Health Jun 2024Insufficient physical activity (PA) is a major risk factor for non-communicable diseases (NCDs) and one of the leading causes of premature mortality worldwide. This...
BACKGROUND
Insufficient physical activity (PA) is a major risk factor for non-communicable diseases (NCDs) and one of the leading causes of premature mortality worldwide. This study examined the prevalence and independent determinants of insufficient PA among adults resident of Tehran utilizing Tehran Cohort Study Data (TeCS).
METHOD
We used the recruitment phase data from the TeCS with complete data on PA. PA was assessed through a Likert-scaled question and categorized into three groups. Utilizing data from the 2016 national census, the age- and sex-weighted prevalence of insufficient PA in Tehran was determined. The adjusted logistic regression model is used to neutralize influencing factors and determine the factors associated with insufficient PA.
RESULT
The weighted prevalence of insufficient PA was 16.9% among the 8213 adult citizens of Tehran, with a greater prevalence among females (19.0% vs. 14.8% among males). Additionally, older age groups, unemployed, housewives, and illiterate educated participants displayed a much higher prevalence of insufficient PA (p < 0.001). Moreover, Tehran's central and southern districts had higher rates of insufficient PA. Concerning the adjusted regression model, older age (Odds ratio [OR]: 4.26, 95% confidence interval [95% CI]: 3.24-5.60, p < 0.001), a lower education level (p < 0.001), unemployment (OR: 1.80, 95% CI: 1.28-2.55, p = 0.001), being a housewife (OR: 1.44, 95% CI: 1.15-1.80, p = 0.002), higher body mass index (BMI) (OR for BMI > 30: 1.85, 95% CI: 1.56-2.18, p < 0.001), opium consumption (OR: 1.92, 95% CI: 1.46-2.52, p < 0.001), diabetes mellitus (OR: 1.25, 95% CI: 1.06-1.48, p = 0.008), hypertension (OR: 1.29, 95% CI: 1.11-1.50, p = 0.001), and coronary artery diseases (OR: 1.30, 95% CI: 1.05-1.61, p = 0.018), were significantly associated with insufficient PA.
CONCLUSIONS
The identified associated factors serve as a valuable guide for policymakers in developing tailored intervention strategies to address the needs of high-risk populations, particularly among older adults and females.
Topics: Humans; Iran; Female; Male; Adult; Middle Aged; Exercise; Cross-Sectional Studies; Prevalence; Young Adult; Risk Factors; Cohort Studies; Aged; Adolescent
PubMed: 38937758
DOI: 10.1186/s12889-024-19201-6 -
BMC Endocrine Disorders Jun 2024The purpose of this study is to investigate the impact of social media-based microlearning (SMBM) on enhancing the knowledge, self-care, and self-efficacy behaviors of... (Randomized Controlled Trial)
Randomized Controlled Trial
The effectiveness of social media-based microlearning in improving knowledge, self-efficacy, and self-care behaviors among adult patients with type 2 diabetes: an educational intervention.
BACKGROUND
The purpose of this study is to investigate the impact of social media-based microlearning (SMBM) on enhancing the knowledge, self-care, and self-efficacy behaviors of patients with type 2 diabetes (T2D) receiving care at a hospital-based diabetes clinic in Zahedan, Iran.
METHODS
This intervention study was conducted from September 2021 to the end of 2022, with an intervention group (SMBM) and a control group (conventional-based training) consisting of patients with T2D. A total of 80 eligible patients were selected using a convenience sampling method and randomly assigned to either the intervention group (n = 40) or the control group (n = 40). The knowledge level, self-care, and self-efficacy of the samples were assessed before and two weeks after the educational intervention. Data analysis was conducted using SPSS version 24, and independent and paired T-tests were used for analysis.
RESULTS
The results of the study revealed that after the intervention, the levels of knowledge, self-care, and self-efficacy in the intervention group were significantly higher than those in the control group (p-value < 0.001).
CONCLUSION
In conclusion, the SMBM appears to be an effective tool for improving self-efficacy, self-care, and knowledge among patients with type 2 diabetes.
Topics: Humans; Diabetes Mellitus, Type 2; Self Efficacy; Male; Female; Middle Aged; Self Care; Social Media; Health Knowledge, Attitudes, Practice; Patient Education as Topic; Iran; Adult; Aged; Follow-Up Studies
PubMed: 38937738
DOI: 10.1186/s12902-024-01626-0 -
BMC Nephrology Jun 2024Salt intake in CKD patients can affect cardiovascular risk and kidney disease progression. Twenty-four hour (24h) urine collections are often used to investigate salt...
BACKGROUND
Salt intake in CKD patients can affect cardiovascular risk and kidney disease progression. Twenty-four hour (24h) urine collections are often used to investigate salt metabolism but are cumbersome to perform. We assessed urinary sodium (U-Na) concentration in spot urine samples and investigated the correlation with 24h U-Na excretion and concentration in CKD patients under nephrological care. Further, we studied the role of CKD stage and diuretics and evaluated the performance of commonly used formulas for the prediction of 24h U-Na excretion from spot urine samples.
METHODS
One hundred eight patients of the German Chronic Kidney Disease (GCKD) study were included. Each participant collected a 24h urine and two spot urine samples within the same period. The first spot urine sample (AM) was part of the second morning urine. The second urine sample was collected before dinner (PM). Patients were advised to take their medication as usual without changing dietary habits. U-Na concentrations in the two spot urine samples and their average ((AM + PM)/2) were correlated with U-Na concentration and total Na excretion in the 24h urine collections. Correlations were subsequently studied after stratification by CKD stage and diuretic intake. The usefulness of three commonly applied equations to estimate 24h U-Na excretion from spot urine samples (Kawasaki, Tanaka and Intersalt) was determined using Bland-Altman plots, analyses of sensitivity, specificity, as well as positive (PPV) and negative predictive values (NPV).
RESULTS
Participants (42 women, 66 men) were on average (± SD) 62.2 (± 11.9) years old, with a mean serum creatinine of 1.6 (± 0.5) mg/dl. 95% had arterial hypertension, 37% diabetes mellitus and 55% were on diuretics. The best correlation with 24h U-Na total excretion was found for the PM spot U-Na sample. We also found strong correlations when comparing spot and 24h urine U-Na concentration. Correction of spot U-Na for U-creatinine did not improve strength of correlations. Neither CKD stage, nor intake of diuretics had significant impact on these correlations. All examined formulas revealed a significant mean bias. The lowest mean bias and the strongest correlation between estimated and measured U-Na excretion in 24h were obtained using the Tanaka-formula. Also, application of the Tanaka-formula with PM U-Na provided best sensitivity, specificity, PPV and NPV to estimate U-Na excretion > 4g/d corresponding to a salt consumption > 10g/d.
CONCLUSION
U-Na concentration of spot urine samples correlated with 24h U-Na excretion especially when PM spot U-Na was used. However, correlation coefficients were relatively low. Neither CKD stage nor intake of diuretics appeared to have an influence on these correlations. There was a significant bias for all tested formulas with the Tanaka-formula providing the strongest correlation with measured 24h U-Na excretion. In summary, using spot urine samples together with the Tanaka-formula in epidemiological studies appears feasible to determine associations between approximate salt intake and outcomes in CKD patients. However, the usefulness of spot-urine samples to guide and monitor salt consumption in individual patients remains limited.
Topics: Humans; Female; Male; Renal Insufficiency, Chronic; Middle Aged; Sodium; Aged; Urine Specimen Collection; Diuretics; Predictive Value of Tests; Urinalysis; Adult
PubMed: 38937680
DOI: 10.1186/s12882-024-03639-2 -
Communications Biology Jun 2024Aggregation of the human islet amyloid polypeptide (hIAPP) contributes to the development and progression of Type 2 Diabetes (T2D). hIAPP aggregates within a few hours...
Aggregation of the human islet amyloid polypeptide (hIAPP) contributes to the development and progression of Type 2 Diabetes (T2D). hIAPP aggregates within a few hours at few micromolar concentration in vitro but exists at millimolar concentrations in vivo. Natively occurring inhibitors of hIAPP aggregation might therefore provide a model for drug design against amyloid formation associated with T2D. Here, we describe the combined ability of low pH, zinc, and insulin to inhibit hIAPP fibrillation. Insulin dose-dependently slows hIAPP aggregation near neutral pH but had less effect on the aggregation kinetics at acidic pH. We determine that insulin alters hIAPP aggregation in two manners. First, insulin diverts the aggregation pathway to large nonfibrillar aggregates with ThT-positive molecular structure, rather than to amyloid fibrils. Second, soluble insulin suppresses hIAPP dimer formation, which is an important early aggregation event. Further, we observe that zinc significantly modulates the inhibition of hIAPP aggregation by insulin. We hypothesize that this effect arose from controlling the oligomeric state of insulin and show that hIAPP interacts more strongly with monomeric than oligomeric insulin.
Topics: Islet Amyloid Polypeptide; Hydrogen-Ion Concentration; Humans; Zinc; Insulin; Protein Aggregates; Diabetes Mellitus, Type 2; Kinetics; Amyloid; Protein Aggregation, Pathological
PubMed: 38937578
DOI: 10.1038/s42003-024-06388-y -
Communications Biology Jun 2024The prevalent RNA alternative splicing (AS) contributes to molecular diversity, which has been demonstrated in cellular function regulation and disease pathogenesis....
The prevalent RNA alternative splicing (AS) contributes to molecular diversity, which has been demonstrated in cellular function regulation and disease pathogenesis. However, the contribution of AS in pancreatic islets during diabetes progression remains unclear. Here, we reanalyze the full-length single-cell RNA sequencing data from the deposited database to investigate AS regulation across human pancreatic endocrine cell types in non-diabetic (ND) and type 2 diabetic (T2D) individuals. Our analysis demonstrates the significant association between transcriptomic AS profiles and cell-type-specificity, which could be applied to distinguish the clustering of major endocrine cell types. Moreover, AS profiles are enabled to clearly define the mature subset of β-cells in healthy controls, which is completely lost in T2D. Further analysis reveals that RNA-binding proteins (RBPs), heterogeneous nuclear ribonucleoproteins (hnRNPs) and FXR1 family proteins are predicted to induce the functional impairment of β-cells through regulating AS profiles. Finally, trajectory analysis of endocrine cells suggests the β-cell identity shift through dedifferentiation and transdifferentiation of β-cells during the progression of T2D. Together, our study provides a mechanism for regulating β-cell functions and suggests the significant contribution of AS program during diabetes pathogenesis.
Topics: Diabetes Mellitus, Type 2; Humans; Alternative Splicing; Single-Cell Analysis; Insulin-Secreting Cells; Sequence Analysis, RNA; Transcriptome; RNA-Binding Proteins; Islets of Langerhans
PubMed: 38937540
DOI: 10.1038/s42003-024-06475-0 -
Scientific Reports Jun 2024Previous studies have reported associations between newly diagnosed diabetes and poor outcomes after percutaneous coronary intervention (PCI), but there is limited data...
Previous studies have reported associations between newly diagnosed diabetes and poor outcomes after percutaneous coronary intervention (PCI), but there is limited data focusing on elderly patients (age ≥ 65). This study aimed to analyze the prevalence and clinical implications of newly diagnosed diabetes in elderly patients who underwent PCI. From 2004 to 2021, a total of 2456 elderly patients who underwent invasive PCI at Korea University Guro Hospital were prospectively enrolled and followed up for a median of five years. The primary endpoint was five-year major adverse cardiovascular events (MACE). Cox regression was used to evaluate whether newly diagnosed diabetes impacted on long-term clinical outcomes. Newly diagnosed diabetes was presented in approximately 8.1% to 10.9% of elderly patients who underwent PCI. Those who had a new diagnosis of diabetes had a higher risk of MACE than previously known diabetes (25.28% vs. 19.15%, p = 0.039). After adjusting for significant factors, newly diagnosed diabetes remained an independent predictor of MACE (HR [hazard ratio] 1.64, 95% confidence interval [CI] 1.24-2.17, p < 0.001), cardiac death (HR 2.15, 95% CI 1.29-3.59, p = 0.003) and repeat revascularization (HR 1.52, 95% CI 1.09-2.11, p = 0.013), but not for non-fatal myocardial infarction (HR 1.66, 95% CI 0.94-2.12, p = 0.081). Newly diagnosed diabetes was associated with an increased risk of 5-year MACE compared with non-diabetes and previously diagnosed diabetes in elderly patients underwent PCI. More attention should be given to those elderly newly diagnosed diabetes population.
Topics: Humans; Percutaneous Coronary Intervention; Aged; Male; Female; Prevalence; Diabetes Mellitus; Risk Factors; Republic of Korea; Aged, 80 and over; Treatment Outcome; Prospective Studies; Proportional Hazards Models
PubMed: 38937534
DOI: 10.1038/s41598-024-65426-1 -
Communications Biology Jun 2024Distinct Natural Killer (NK)-like CD57 and PD-1 CD8 exhausted-like T cell populations (Tex) have both been linked to beneficial immunotherapy response in autoimmune type...
Distinct Natural Killer (NK)-like CD57 and PD-1 CD8 exhausted-like T cell populations (Tex) have both been linked to beneficial immunotherapy response in autoimmune type 1 diabetes (T1D) patients. The origins and relationships between these cell types are poorly understood. Here we show that while PD-1 and CD57 Tex populations are epigenetically similar, CD57 Tex cells display unique increased chromatin accessibility of inhibitory Killer Cell Immunoglobulin-like Receptor (iKIR) and other NK cell genes. PD-1 and CD57 Tex also show reciprocal expression of Inhibitory Receptors (IRs) and iKIRs accompanied by chromatin accessibility of Tcf1 and Tbet transcription factor target sites, respectively. CD57 Tex show unappreciated gene expression heterogeneity and share clonal relationships with PD-1 Tex, with these cells differentiating along four interconnected lineage trajectories: Tex-PD-1, Tex-CD57, Tex-Branching, and Tex-Fluid. Our findings demonstrate new relationships between Tex-like populations in human autoimmune disease and suggest that modulating common precursor populations may enhance response to autoimmune disease treatment.
Topics: Diabetes Mellitus, Type 1; Humans; CD8-Positive T-Lymphocytes; Killer Cells, Natural; Programmed Cell Death 1 Receptor; CD57 Antigens; Cell Lineage; Hepatocyte Nuclear Factor 1-alpha; Female; Male; Adult
PubMed: 38937521
DOI: 10.1038/s42003-024-06456-3 -
Nature Communications Jun 2024Recent studies have shown the crucial role of podocyte injury in the development of diabetic kidney disease (DKD). Deubiquitinating modification of proteins is widely...
Recent studies have shown the crucial role of podocyte injury in the development of diabetic kidney disease (DKD). Deubiquitinating modification of proteins is widely involved in the occurrence and development of diseases. Here, we explore the role and regulating mechanism of a deubiquitinating enzyme, OTUD5, in podocyte injury and DKD. RNA-seq analysis indicates a significantly decreased expression of OTUD5 in HG/PA-stimulated podocytes. Podocyte-specific Otud5 knockout exacerbates podocyte injury and DKD in both type 1 and type 2 diabetic mice. Furthermore, AVV9-mediated OTUD5 overexpression in podocytes shows a therapeutic effect against DKD. Mass spectrometry and co-immunoprecipitation experiments reveal an inflammation-regulating protein, TAK1, as the substrate of OTUD5 in podocytes. Mechanistically, OTUD5 deubiquitinates K63-linked TAK1 at the K158 site through its active site C224, which subsequently prevents the phosphorylation of TAK1 and reduces downstream inflammatory responses in podocytes. Our findings show an OTUD5-TAK1 axis in podocyte inflammation and injury and highlight the potential of OTUD5 as a promising therapeutic target for DKD.
Topics: Podocytes; Animals; MAP Kinase Kinase Kinases; Diabetic Nephropathies; Mice; Inflammation; Ubiquitination; Humans; Mice, Knockout; Male; Mice, Inbred C57BL; Phosphorylation; Diabetes Mellitus, Experimental; Ubiquitin-Specific Proteases; HEK293 Cells; Deubiquitinating Enzymes
PubMed: 38937512
DOI: 10.1038/s41467-024-49854-1 -
NPJ Science of Food Jun 2024Diabetes mellitus affected more than 500 million of people globally, with an annual mortality of 1.5 million directly attributable to diabetic complications. Oxidative...
Diabetes mellitus affected more than 500 million of people globally, with an annual mortality of 1.5 million directly attributable to diabetic complications. Oxidative stress, in particularly in post-prandial state, plays a vital role in the pathogenesis of the diabetic complications. However, oxidative status marker is generally poorly characterized and their mechanisms of action are not well understood. In this work, we proposed a new framework for deep characterization of oxidative stress in erythrocytes (and in urine) using home-built micro-scale NMR system. The dynamic of post-prandial oxidative status (against a wide variety of nutritional load) in individual was assessed based on the proposed oxidative status of the red blood cells, with respect to the traditional risk-factors such as urinary isoprostane, reveals new insights into our understanding of diabetes. This new method can be potentially important in drafting guidelines for sub-stratification of diabetes mellitus for clinical care and management.
PubMed: 38937488
DOI: 10.1038/s41538-024-00282-x