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Background: Obesity and overweight, as determined by the body mass index (BMI), are harmful to metabolic health. However, the BMI can not reflect body composition or fat distribution. The fat-free mass index (FFMI) and the fat mass index (FMI) can provide more information on body composition. The aim of the observational research was to determine whether the FMI and the FFMI are significantly associated with the risk of developing diabetes and prediabetes. Methods: The investigators included data for 10,085 National Health and Nutrition Examination Survey (2011–2018) participants aged over 20 years who underwent dual-energy X-ray absorptiometry (DXA). The FFMI and the FMI were determined based on total fat mass and lean mass measured by DXA. Diabetes and prediabetes status were determined by medical history and laboratory examination. Logistic regression analyses were performed to explore the correlations between the FMI/FFMI and the risk of developing diabetes/prediabetes. Restricted cubic spline analysis was used to explore underlying nonlinear associations. Results: In the present study, 1,135 patients were diagnosed with diabetes, 3,258 had prediabetes, and 5,692 were classified as control participants. The FFMI (odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.04–1.16) and the FMI (OR = 1.08, 95% CI = 1.04–1.12) were independently related to an increased risk of developing diabetes. Moreover, the FFMI (OR 1.08, 95% CI 1.02–1.16) and the FMI (OR 1.07, 95% CI 1.02–1.13) also independently correlated with a rising risk of developing prediabetes. The restricted cubic spline (RCS) outcomes suggested that the associations are approximately linear. Conclusions: Both the FMI and the FFMI significantly correlated with the danger of developing diabetes and prediabetes, and the correlations are approximately linear. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the interaction of urinary protein-to-creatinine ratio (UPCR) with diabetes on the risk of cardiovascular events in a cohort study. Methods: The study population consisted of 639 participants with chronic kidney disease (CKD) stages 2–5, enrolled between 2010 and 2011 in Japan. Cox proportional hazards models were used to evaluate the independent and combined effects of the UPCR and diabetes on cardiovascular events. Results: During a median follow-up of 3 years, 59 participants developed cardiovascular events during follow-up. A notably higher risk of cardiovascular events was found in participants with proteinuria [hazards ratio (HR): 2.16, 95% confidence interval (95% CI): 1.17–3.97] compared to those without proteinuria at UPCR levels. In addition, the participants with diabetes had a higher risk of cardiovascular events (HR: 2.53, 95% CI: 1.49–4.30) than those without diabetes. Moreover, an interaction was found between UPCR and diabetes on cardiovascular events (P for interaction = 0.04). Participants with both proteinuria (UPCR ≥ 0.5 g/gCr) and diabetes had a 4.09 times higher risk of cardiovascular events (HR: 4.09, 95% CI: 1.97–8.47) compared with those without proteinuria (UPCR < 0.5 g/gCr) and diabetes. Conclusions: In summary, among participants with CKD stages 2–5, proteinuria and diabetes were found to independently and jointly affect the risk of cardiovascular events. Participants with proteinuria and diabetes had the highest risk of cardiovascular events compared with other groups. [ABSTRACT FROM AUTHOR]

Background: The rewiring of molecular interactions in various conditions leads to distinct phenotypic outcomes. Differential network analysis (DINA) is dedicated to exploring these rewirings within gene and protein networks. Leveraging statistical learning and graph theory, DINA algorithms scrutinize alterations in interaction patterns derived from experimental data. Results: Introducing a novel approach to differential network analysis, we incorporate differential gene expression based on sex and gender attributes. We hypothesize that gene expression can be accurately represented through non-Gaussian processes. Our methodology involves quantifying changes in non-parametric correlations among gene pairs and expression levels of individual genes. Conclusions: Applying our method to public expression datasets concerning diabetes mellitus and atherosclerosis in liver tissue, we identify gender-specific differential networks. Results underscore the biological relevance of our approach in uncovering meaningful molecular distinctions. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication with well-established adverse effects on maternal and fetal health. However, research on its impact on sexual health is inconsistent. Currently, there is no comprehensive review on sexual function in pregnant women with GDM. The purpose of this study is to systematically gather and synthesize the available evidence, addressing this important research gap. Methods: This systematic review and meta-analysis utilized a comprehensive literature search strategy and incorporated the following databases: the Cochrane Library, Scopus, PubMed, Web of Science, SID, and Google Scholar. The search was conducted until February 21, 2024. The quality of the cross-sectional and case‒control studies included in the current study was evaluated via the modified and standard Newcastle‒Ottawa scale. The certainty of the evidence was evaluated via the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. A meta-regression was conducted to examine the variables that influence total sexual function. Additionally, sequential analysis was performed to determine the required information size for the meta-analysis. Results: The systematic search process yielded a total of 370 studies. The final analysis included six studies. The meta-analysis findings revealed that compared with controls, women with GDM had significantly lower total scores for sexual function (SMD − 1.80, 95% CI -3.44 to -0.15, p = 0.03), sexual desire (SMD − 5.14, 95% CI -8.14 to -2.14, p < 0.001), arousal (SMD − 0.58, 95% CI -0.95 to -0.21, p = 0.002), lubrication (MD -0.41, 95% CI -0.59 to -0.22, p < 0.001) and satisfaction (SMD − 3.82, 95% CI -6.08 to -1.57, p < 0.001). However, the analysis did not reveal statistically significant differences in sexual pain, or orgasm between the GDM and control groups. The meta-regression analysis revealed that older age in the control group was associated with poorer sexual function. Conclusion: Compared with control women, pregnant women diagnosed with GDM have lower sexual function. Further research with larger sample sizes is necessary to enhance the robustness of the evidence, given the low level of certainty. Healthcare providers should focus on the sexual well-being of women with GDM and create tailored interventions to address their specific needs. [ABSTRACT FROM AUTHOR]

Coronary artery disease has a high mortality rate and is a striking public health concern, affecting a substantial portion of the global population. On the early onset of myocardial ischemia, thrombolytic therapy and coronary revascularization could promptly restore the bloodstream and nutrient supply to the ischemic tissue, efficiently preserving less severely injured myocardium. However, the abrupt re-establishment of blood flow triggers the significant discharge of previously accumulated oxidative substances and inflammatory cytokines, leading to further harm referred to as ischemia/reperfusion (I/R) injury. Diabetes significantly raises the vulnerability of the heart to I/R injury due to disrupted glucose and lipid processing, impaired insulin sensitivity and metabolic signaling, and increased inflammatory responses. Numerous studies have indicated that adipokines are crucial in the etiology and pathogenesis of obesity, diabetes, hyperlipidemia, hypertension, and coronary artery disease. Adipokines such as adiponectin, adipsin, visfatin, chemerin, omentin, and apelin, which possess protective properties against inflammatory activity and insulin resistance, have been shown to confer myocardial protection in conditions such as atherosclerosis, myocardial hypertrophy, myocardial I/R injury, and diabetic complications. On the other hand, adipokines such as leptin and resistin, known for their pro-inflammatory characteristics, have been linked to elevated cardiac lipid deposition, insulin resistance, and fibrosis. Meteorin-like (metrnl) exhibits opposite effects in various pathological conditions. However, the data on adipokines in myocardial I/R, especially in diabetes, is still incomplete and controversial. This review focuses on recent research regarding the categorization and function of adipokines in the heart muscle, and the identification of different signaling pathways involved in myocardial I/R injury under diabetic conditions, aiming to facilitate the exploration of therapeutic strategies against myocardial I/R injury in diabetes. [ABSTRACT FROM AUTHOR]

Background: A common genetic variant at the glutamate-ammonia ligase (GLUL) locus has been previously associated with an increased risk of coronary artery disease (CAD) as well as alterations of glutamic acid metabolism and the γ-glutamyl cycle in individuals with type 2 diabetes (T2D). Here we investigated whether less frequent variants in GLUL and 15 additional genes in these pathways are associated with differences in CAD risk in T2D. Methods: Coding sequences and regulatory elements of these genes were sequenced in 2,394 individuals with T2D from three CAD case/control sets. Results: Ninety-six variants with minor allele frequency [MAF]< 0.05 were identified as being nominally associated with CAD status. One of these variants (rs62447457, MAF 0.025), placed in a non-coding region flanking the γ-glutamylcyclotransferase (GGCT) gene, showed nominal evidence of replication in two other cases-control sets (n = 1,132), with summary OR of 0.54 (p = 2.5 × 10–4). Another variant (rs145322388, MAF = 0.039), flanking the dipeptidase 2 (DPEP2) gene, showed association with CAD status across discovery and replications sets (summary OR 0.61, p = 2.5 × 10–4). A third variant (rs1238275622, MAF 0.004), flanking the GLUL gene, was associated with increased risk of CAD (summary OR 1.84, p-value 2.1 × 10–3). Based on their Regulome scores (2b, 2a, and 3a, respectively), all three variants are very likely to have regulatory functions. Conclusions: In summary, we have identified low-frequency variants associated with CAD in T2D at two loci involved in glutamic acid metabolism and the γ-glutamyl cycle. These findings provide further evidence for a role of these pathways in the link between T2D and CAD. [ABSTRACT FROM AUTHOR]

Background: Education during pregnancy is important for the development of the pregnant woman's ability to adapt to change and for a healthy birth. In this study, we aimed to examine the effects of education through a diabetes education program on maternal and newborn health in women diagnosed with gestational diabetes. Materials and methods: In our study, we compared the maternal and neonatal health outcomes of pregnant women who participated in the diabetes education program and were diagnosed with gestational diabetes with the outcomes of pregnant women who did not participate in the diabetes education program and were diagnosed with gestational diabetes. The study included patients who were diagnosed with diabetes between 24and 26 weeks gestation at a tertiary education and research hospital and who underwent a 75-gram OGTT test. Age, BMI, parity, method of delivery, weight gain during pregnancy, newborn birth weight, gestational age and Apgar scores were compared. Results: The study included 119 patients and analyzed maternal-neonatal outcomes. There were no statistically significant differences in age (33 ± 5.7 versus 31 ± 5.2), body mass index (BMI) (32.2 vs. 31.2), gravidity, parity, number of miscarriages, mode of delivery, family history of diabetes, smoking, prenatal corticosteroid use, and gestational age at delivery. The HbA1c value (p: 0.013), the total weight gain during pregnancy (p: 0.015), the need for insulin treatment (p: 0.002), and the birth weight (0.005) were significantly higher in the group without diabetes education. Conclusion: In our study, diabetic school education was associated with lower HbA1c levels, less weight gain and less need for insulin therapy. When the results were categorized by insulin use, it was found that in patients using insulin, those who received diabetic school education had fewer macrosomic fetuses, whereas in patients not using insulin, those who received diabetic school education had lower maternal weight gain during pregnancy. [ABSTRACT FROM AUTHOR]

Background: In 2016, Uganda introduced services for hypertension and diabetes in selected HIV clinics. We evaluated the costs associated with scaling up these services in HIV clinics in Mbarara and Ibanda districts, Uganda. Methods: We estimated the annual costs of providing hypertension and diabetes services using an activity-based costing approach from the health system perspective in ten randomly selected HIV clinics in Mbarara and Ibanda districts. Cost inputs included 2023 data on costs of medications, health provider time, salaries, training costs, and monitoring costs. We determined the average annual cost and medication costs for hypertension and diabetes treatment per enrolled adult patient, stratified by type of health facility. Results: The total annual cost of hypertension and diabetes management services in ten selected HIV clinics was estimated to be $413,850 (range: $8,386 − 186,973). The annual average clinic-level cost per enrolled patient was estimated at $14 (range: $7 − 31). Of the total annual cost, the cost of provider time for initial and follow-up visits represented the largest cost component in 5/10 clinics (mean: 37%, range [13–58%]). In 4/10 clinics, the major cost components were the costs of medication, diagnostic tests, and related supplies (mean: 37%, range [10–75%]). The average cost per enrolled adult patient was $11 at public facilities and $21 in private not-for-profit facilities. The average medication cost per patient for hypertension was $24 (range: $7 − 97) annually; $13 at public facilities and $50 at private not-for-profit facilities. For diabetes treatment, the average annual medication cost per patient was estimated at $14 (range: $6 − 35); $11 at public facilities and $22 at private not-for-profit facilities. Conclusion: Adding hypertension and diabetes management to routine HIV care might be feasible based on the estimated annual cost per patient. Hypertension and diabetes treatment was more costly in private not-for-profit facility-based clinics than at public facilities. This variation was primarily driven by higher medication procurement prices at private facilities, revealing a potential area for optimizing costs through improved procurement practices. [ABSTRACT FROM AUTHOR]

Background: Type 1 diabetes, an autoimmune disorder leading to the destruction of pancreatic β-cells, requires lifelong insulin therapy. Islet transplantation offers a promising solution but faces challenges such as limited availability and the need for immunosuppression. Induced pluripotent stem cells (iPSCs) provide a potential alternative source of functional β-cells and have the capability for large-scale production. However, current differentiation protocols, predominantly conducted in hybrid or 2D settings, lack scalability and optimal conditions for suspension culture. Methods: We examined a range of bioreactor scaleup process parameters and quality target product profiles that might affect the differentiation process. This investigation was conducted using an optimized High Dimensional Design of Experiments (HD-DoE) protocol designed for scalability and implemented in 0.5L (PBS-0.5 Mini) vertical wheel bioreactors. Results: A three stage suspension manufacturing process is developed, transitioning from adherent to suspension culture, with TB2 media supporting iPSC growth during scaling. Stage-wise optimization approaches and extended differentiation times are used to enhance marker expression and maturation of iPSC-derived islet-like clusters. Continuous bioreactor runs were used to study nutrient and growth limitations and impact on differentiation. The continuous bioreactors were compared to a Control media change bioreactor showing metabolic shifts and a more β-cell-like differentiation profile. Cryopreserved aggregates harvested from the runs were recovered and showed maintenance of viability and insulin secretion capacity post-recovery, indicating their potential for storage and future transplantation therapies. Conclusion: This study demonstrated that stage time increase and limited media replenishing with lactate accumulation can increase the differentiation capacity of insulin producing cells cultured in a large-scale suspension environment. [ABSTRACT FROM AUTHOR]

Background: Vascular calcification is a major contributor to cardiovascular disease, especially diabetes, where it exacerbates morbidity and mortality. Although pyrophosphate is a recognized natural inhibitor of vascular calcification, there have been no prior studies examining its specific deficiency in diabetic conditions. This study is the first to analyze the direct link between elevated glucose levels and disruptions in extracellular pyrophosphate metabolism. Methods: Rat aortic smooth muscle cells, streptozotocin (STZ)-induced diabetic rats, and diabetic human aortic smooth muscle cells were used to assess the effects of elevated glucose levels on pyrophosphate metabolism and vascular calcification. The techniques used include extracellular pyrophosphate metabolism assays, thin-layer chromatography, phosphate-induced calcification assays, BrdU incorporation for DNA synthesis, aortic smooth muscle cell viability and proliferation assays, and quantitative PCR for enzyme expression analysis. Additionally, extracellular pyrophosphate metabolism was examined through the use of radiolabeled isotopes to track ATP and pyrophosphate transformations. Results: Elevated glucose led to a significant reduction in extracellular pyrophosphate across all diabetic models. This metabolic disruption was marked by notable downregulation of both the expression and activity of ectonucleotide pyrophosphatase/phosphodiesterase 1, a key enzyme that converts ATP to pyrophosphate. We also observed an upregulation of ectonucleoside triphosphate diphosphohydrolase 1, which preferentially hydrolyzes ATP to inorganic phosphate rather than pyrophosphate. Moreover, tissue-nonspecific alkaline phosphatase activity was markedly elevated across all diabetic models. This shift in enzyme activity significantly reduced the pyrophosphate/phosphate ratio. In addition, we noted a marked downregulation of matrix Gla protein, another inhibitor of vascular calcification. The impaired pyrophosphate metabolism was further corroborated by calcification experiments across all three diabetic models, which demonstrated an increased propensity for vascular calcification. Conclusions: This study demonstrated that diabetes-induced high glucose disrupts extracellular pyrophosphate metabolism, compromising its protective role against vascular calcification. These findings identify pyrophosphate deficiency as a potential mechanism in diabetic vascular calcification, highlighting a new therapeutic target. Strategies aimed at restoring or enhancing pyrophosphate levels may offer significant potential in mitigating cardiovascular complications in diabetic patients, meriting further investigation. [ABSTRACT FROM AUTHOR]

Background: Autonomy-supporting interventions may be a prerequisite to achieve better long-term management of type 2 diabetes. Evidence suggests that the guided self-determination (GSD) method might improve haemoglobin A1c and diabetes distress in people with type 1 diabetes. The evidence of an effect of a GSD intervention compared with an attention control group in adults with type 2 diabetes is unknown. Methods/design: The trial is designed as a pragmatic, investigator-initiated, dual-centre, randomised, parallel-group, assessor-blinded, superiority clinical trial of persons with type 2 diabetes. A nurse will administer GSD intervention versus an attention control. The primary outcome is diabetes distress, and secondary outcomes are quality of life, depressive symptoms, and non-serious adverse events. Exploratory outcomes are haemoglobin A1c, motivation, and serious adverse events. Participants are assessed at baseline, 5-, and 12-month follow-up. Here, we present a detailed, comprehensive plan of all statistical analyses, including methods to handle missing data, and assessments of the underlying statistical assumptions. The statistical analyses will be conducted independently by two statisticians following the present plan. Discussion: To mitigate the risk of analysis bias and increase the validity of the OVEROME trial, this statistical analysis plan was developed prior to unblinding of the trial results in concordance with the Declaration of Helsinki and the Conference on Harmonization of Good Clinical Practice Guidelines. Trial registration: ClinicalTrials.gov NCT 04601311. Registered on October 2020. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies have suggested diabetic patients should synchronize their foods and nutrient intake with their biological rhythm; however, the optimal intake time of coffee and tea for reducing all-cause and disease-specific mortality in diabetes is still unknown. This study aims to examine by investigating the association of timing for coffee and tea consumption with long-term survival in people with diabetes. Methods: A total of 5378 people with diabetes who enrolled in the National Health and Nutrition Examination Survey from 2003 to 2014 were recruited for this study. Coffee and tea intakes were measured by a 24-h dietary recall, which were divided by different time intervals across the day, including dawn to forenoon, forenoon to noon, noon to evening, and evening to dawn. Weighted cox proportional hazards regression models were developed to evaluate the survival-relationship of coffee and tea consumption with mortality of all-cause, cardiovascular disease (CVD), stroke, and diabetes. Results: During 47,361 person-year follow up, total 1639 death cases were documented, including 731 CVD deaths, 467 heart disease deaths, 99 stroke deaths, and 462 diabetes deaths. After adjustment for potential confounders, compared with participants without drinking coffee during dawn to forenoon, drinking coffee at this period was associated with increased mortality risk of all-cause (HR 1.25, 95% CI 1.05–1.50), CVD (HR 1.41, 95% CI 1.07–1.86), heart-disease (HR 1.47, 95% CI 1.05–2.07), and diabetes (HR 1.50, 95% CI 1.10–2.04). In contrast, drinking coffee during forenoon to noon had lower mortality risk of all-cause (HR 0.80, 95% CI 0.69–0.92), CVD (HR 0.79, 95% CI 0.63–0.99), and heart disease (HR 0.70, 95% CI 0.52–0.94). Similarly, drinking tea during forenoon to noon had lower risk of CVD mortality (HR = 0.62, 95% CI 0.44–0.87). Conclusions: This study suggests that drinking coffee in dawn to forenoon is linked to a higher risk of death, but having coffee and tea from forenoon to noon is linked to a lower risk of overall mortality, CVD, and heart disease in individuals with diabetes. [ABSTRACT FROM AUTHOR]

Aim: This pre-post intervention study aimed to assess the relationship between baseline dietary quality and the efficacy of a dietitian-guided weight reduction program, which has not been thoroughly documented to date. Methods: Ninety-two consecutive obese or overweight patients visiting a tertiary center clinic for weight reduction were enrolled in this study. Participants received a dietitian-guided weight reduction education program aimed at reducing daily caloric intake by 500 kcal and improving adherence to the Mediterranean diet for 3 months. Baseline dietary quality was assessed using the 14-item Taiwanese Mediterranean Diet Adherence Screener (T-MEDAS), where a higher T-MEDAS score reflects greater adherence to the Mediterranean diet. Additional covariates, including dietary behaviors, lifestyle factors, and comorbidities were also recorded. The primary outcome was the percentage of weight reduction at 3 months, analyzed using restricted cubic spline models and generalized estimating equations (GEE) to account for the correlation between weight change and the baseline T-MEDAS scores. Results: Thirty-nine participants were excluded due to major illnesses, use of anti-obesity medications, or loss to follow-up. Among the remaining 53 participants (mean age 41.2 ± 12.8 years, 56.6% female), the average weight reduction was 3.9 ± 3.3% from a baseline weight of 98.5 ± 12.8 kg. Participants who did not achieve a weight reduction of more than 5% had higher baseline T-MEDAS scores compared to those who did (5.4 ± 1.7 vs. 4.1 ± 1.8, p = 0.026). A restricted cubic spline model, adjusted for covariates including age, gender, diabetes mellitus (DM), dyslipidemia, and smoking, revealed a significant inverse relationship between higher baseline T-MEDAS scores and weight loss. After controlling for various confounders, GEE analysis demonstrated that higher baseline T-MEDAS scores were significantly associated with less weight loss (beta: -4.1, 95% CI: -5.6 to -2.6, p < 0.001). Conclusions: Higher baseline dietary quality was associated with reduced effectiveness of a dietitian-guided weight reduction program. This suggests that additional strategies may be required to improve the success of weight loss interventions in individuals with higher baseline dietary quality. [ABSTRACT FROM AUTHOR]

Background: A lower dietary sodium intake has been associated with a reduced risk of cardiovascular disease (CVD) mortality in the general population. However, the evidence is less clear in diabetic patients. The study aims to investigate whether the usage of table salt is associated with all-cause and CVD mortality among individuals with diabetes. Methods: In this prospective cohort study, participants with diabetes from the U.S. National Health and Nutritional Examination Survey (NHANES) 2003–2018 were included. Weighted linear regression models were employed to assess the association between the usage of table salt and dietary sodium intake. Weighted Cox proportional hazards regression models were used to assess the association between the usage of table salt and all-cause and CVD mortality. Results: This cohort study included data from 6,258 participants in analysis. During 44,035 person-years of follow-up, 1,504 deaths from all-causes and 427 from CVD were documented. Not using table salt was significantly associated with lower dietary sodium intake, with a β of -192.60 (95% CI, -297.01 to -88.18) mg. A higher risk of all-cause and CVD mortality was observed in the group of participants not using table salt among patients with diabetes. Compared with participants using table salt, the hazard ratios for all-cause mortality were 1.18 (95% CI, 1.03 to 1.35), and for CVD were 1.48 (95 CI, 1.16 to 1.90) for participants not using table salt. The subgroup analysis revealed a significantly stronger link between the usage of table salt and all-cause mortality in participants with CVD (P for interaction = 0.004). Conclusions: This study indicated that not using table salt was associated with a lower dietary sodium intake, and an increased risk of all-cause and CVD mortality among individuals with diabetes. Interventional studies are needed to determine more beneficial relevant approaches to dietary management in diabetes care. [ABSTRACT FROM AUTHOR]

Background: Diabetes is a major public health issue, and over half a billion people are estimated to be living with diabetes, with 6.7 million deaths reported in 2021. The global diabetes burden has been recognised and included in the United Nations Sustainable Development Goals to achieve a zero increase in diabetes cases and reduce one-third of premature diabetes deaths by 2030. However, local beliefs about the causes of diabetes have affected its prevention and management. This study examined community beliefs and practices about diabetes and how they affect the prevention and management of diabetes in the community. Methods: This study was carried out in the Ho Municipality of the Volta Region of Ghana. We conducted 33 in-depth interviews with 18 patients with diabetes, 5 carers (caretakers of patients with diabetes), 3 traditional healers, 2 religious leaders, 3 community elders, and 2 assembly members who were purposefully selected from urban and rural areas across the municipality. The interviews were recorded digitally and transcribed verbatim. Thematic analysis was applied to analyse the data using QRS NVivo 20. Results: Diabetes was described locally as sukli dɔ (sugar disease), which affects humans. Diabetes is believed to be caused by spiritual forces (juju, bewitchment, and punishment from gods) and physical factors (unhealthy diet, physical inactivity, eating fruits and vegetables sprayed with pesticides and insecticides, sugary and starchy foods, smoking, and abuse of alcohol). In terms of the management of diabetes, participants said traditional remedies are performed for spiritual interpretation, deliverance, fortification, and cleansing before biomedical and physical remedies are sought. Diabetes was likened to HIV/AIDS, and the sufferers were described as bringing the condition upon themselves as a result of their bad deeds. They were stigmatised, coupled with delays at the hospital, and poverty has also affected the prevention and management of diabetes. Conclusion: The local belief that diabetes is caused by spiritual forces, likened to HIV/AIDS, delays at hospitals, and poverty, has affected the prevention and management of diabetes. Incorporating local beliefs and practices into the intervention design using culturally sensitive health education programmes and improving social determinants of health may help improve the prevention and management of diabetes in communities. [ABSTRACT FROM AUTHOR]

Background: Children with chronic illnesses pose a significant burden on parents who are directly involved in caregiving. Despite the high prevalence of chronic illnesses among children in Saudi Arabia, no study has examined caregiver burden and other related factors in the Saudi Population. Thus, this study determined the levels of caregiver burden, perceived social support, and perceived stress and their association among parents who provide care to their child with a chronic illness. Methods: A cross-sectional design was used for this study. Data were collected through an online survey using standardized scales from parents who had at least one child suffering from a chronic illness or disability for more than 12 months and requiring continuous medical treatment. Results: A total of 206 parents reported mild-to-moderate levels of caregiver burden, moderate levels of perceived stress, and high levels of perceived social support. Furthermore, perceived social support was significantly correlated with caregiver burden (rho = − 0.36, p < 0.01) and perceived stress (rho = − 0.45, p < 0.01), and caregiver burden was significantly associated with perceived stress (rho = 0.65, p < 0.01). Conclusions: Study findings suggest that social support could play a pivotal role in designing intervention programs to mitigate the stress caused by the caregiver burden. This insight underscores the urgent need for policymakers to develop psychosocial interventions and targeted programs for caregivers of children with chronic illnesses. [ABSTRACT FROM AUTHOR]

Background: The Metabolic Insulin Resistance Score (METS-IR) is a non-invasive proxy for insulin resistance (IR) that has been newly developed in recent years and has been shown to be associated with diabetes risk. Our aim was to assess the predictive value of METS-IR for the future development of diabetes and its temporal differences in people of different sex, age, and body mass index (BMI). Methods: The current study included 15,453 baseline non-diabetic subjects in the NAGALA cohort and then grouped according to the World Health Organization's (WHO) recommended criteria for age and BMI. Multivariate Cox regression and time-dependent receiver operator characteristics (ROC) curves were used to analyze the value of METS-IR in assessing and predicting the risk of diabetes in people of different sexes, ages, and BMIs. Results: 373 individuals developed diabetes during the observation period. By multivariate COX regression analysis, the development of future diabetes was significantly associated with increased METS-IR, and this positive association was stronger in women than in men and in individuals < 45 years than in individuals ≥ 45 years; while no significant differences were observed between non-obese and overweight/obesity individuals. Using time-dependent ROC analysis we also assessed the predictive value of METS-IR for future diabetes at a total of 11-time points between 2 and 12 years. The results showed that METS-IR had a higher predictive value for the future development of diabetes in women or individuals < 45 years of age compared to men or individuals ≥ 45 years of age for almost the entire follow-up period. Furthermore, across different BMI categories, we also found that in the short term (3–5 years), METS-IR had a higher predictive value for the development of diabetes in individuals with overweight/obesity, while in the medium to long term (6–12 years), METS-IR was more accurate in predicting the development of diabetes in non-obese individuals. Conclusions: Our study showed that METS-IR was independently associated with the development of future diabetes in a non-diabetic population. METS-IR was a good predictor of diabetes, especially for women and individuals < 45 years old for predicting the future risk of developing diabetes at all times. [ABSTRACT FROM AUTHOR]

Background: Hematopoiesis within the bone marrow (BM) is a complex and tightly regulated process predominantly influenced by immune factors. Aging, diabetes, and obesity are significant contributors to BM niche damage, which can alter hematopoiesis and lead to the development of clonal hematopoiesis of intermediate potential (CHIP). Genetic/epigenetic alterations during aging could influence BM niche reorganization for hematopoiesis or clonal hematopoiesis. CHIP is driven by mutations in genes such as Tet2, Dnmt3a, Asxl1, and Jak2, which are associated with age-related hematological malignancies. Objective: This literature review aims to provide an updated exploration of the functional aspects of BM niche cells within the hematopoietic microenvironment in the context of age-related hematological malignancies. The review specifically focuses on how immunological stressors modulate different signaling pathways that impact hematopoiesis. Methods: An extensive review of recent studies was conducted, examining the roles of various BM niche cells in hematopoietic stem cell (HSC) trafficking and the development of age-related hematological malignancies. Emphasis was placed on understanding the influence of immunological stressors on these processes. Results: Recent findings reveal a significant microheterogeneity and temporal stochasticity of niche cells across the BM during hematopoiesis. These studies demonstrate that niche cells, including mesenchymal stem cells, osteoblasts, and endothelial cells, exhibit dynamic interactions with HSCs, significantly influenced by the BM microenvironment as the age increases. Immunosurveillance plays a crucial role in maintaining hematopoietic homeostasis, with alterations in immune signaling pathways contributing to the onset of hematological malignancies. Novel insights into the interaction between niche cells and HSCs under stress/aging conditions highlight the importance of niche plasticity and adaptability. Conclusion: The involvement of age-induced genetic/epigenetic alterations in BM niche cells and immunological stressors in hematopoiesis is crucial for understanding the development of age-related hematological malignancies. This comprehensive review provides new insights into the complex interplay between niche cells and HSCs, emphasizing the potential for novel therapeutic approaches that target niche cell functionality and resilience to improve hematopoietic outcomes in the context of aging and metabolic disorders. Novelty statement: This review introduces novel concepts regarding the plasticity and adaptability of BM niche cells in response to immunological stressors and epigenetics. It proposes that targeted therapeutic strategies aimed at enhancing niche cell resilience could mitigate the adverse effects of aging, diabetes, and obesity on hematopoiesis and clonal hematopoiesis. Additionally, the review suggests that understanding the precise temporal and spatial dynamics of niche-HSC interactions and epigenetics influence may lead to innovative treatments for age-related hematological malignancies. [ABSTRACT FROM AUTHOR]

Background: Green synthesized nanoparticles have recently gained significant medicinal applications and oftentimes outperform their green sources. Selenium is of fundamental importance to human health, stemming from its distinctive physicochemical properties, such as antioxidant activity, inhibition of Lipid peroxidation, stabilization of membrane proteins, maintenance of membrane fluidity and modulation of cell signaling. Though reports have shown some therapeutic potential of Ackee plant parts such as antioxidant, anti-inflammatory, antimicrobial, neuroprotective, very few scientific proofs still exist in support of these effects. Methods: This study synthesized selenium nanoparticles (Se-NPs) from crude methanolic extracts of Ackee leaves (AKL) and Ackee arils (AKA), examined the photo-physical characteristics of the Se-NPs and determined the in-vitro antioxidant, antidiabetic, and anti-inflammatory potentials of AKL, AKA, and their Se-NPs using established protocols. Results: In both leaves and arils Se-NPs: UV spectroscopy revealed a qualitative absorbance at 310 nm; FTIR indicated multiple vibrations around 4000 cm−1- 400 cm−1; SEM images of 5 µm principally showed consistent size distribution of amorphous and granular shape at a magnification of 10,000X; while EDS spectra strongly confirm the presence of atomic Se compound at 30 kV. Various antioxidant activities assays carried out showed a range of approximately 4 to 60 times higher activities of the AKL, AKA, and Se-NPs than Ascorbic acid—the standard drug used. Furthermore, appreciable activities of more than 50% were obtained for alpha-amylase and alpha-glucosidase inhibitory activities, along with highly significant activities of haemoglobin glycosylation, glucose uptake, membrane stabilization, anti-arthritic, anti-haemolysis activities, when AKL, AKA, and Se-NPs were compared with standard drugs. Conclusion: Encouraging the development and utilization of AKL, AKA, and Se-NPs will provide tremendous therapeutic efficacy and bioavailability approaches towards the management of diabetes, inflammation, and other oxidative stress-related diseases. [ABSTRACT FROM AUTHOR]

Background: Recent reports have revealed that nephropathy leading to kidney injury (KI) is a prevalent complication of COVID-19 and is linked to high mortality and morbidity in diabetes mellitus type II (DM-T-II) patients. This systematic literature review and meta-analysis aimed to critically analyze existing studies and evidence on the impact of COVID-19 on nephropathy and kidney injury in diabetes mellitus type II (DM-T-II) patients. Method: A systematic search was conducted in the Web of Science (WoS), PubMed and Cochrane databases for relevant studies published between March 2020 and July 2023. To ensure the integrity of the systematic literature review and meta-analysis, observational studies that specifically reported post-COVID-19 kidney injury in DM-T2 patients were included, whereas we did not include articles in the press, meta-analyses, case reports, case series, Diabetes Type-I articles or non-English papers. The primary outcome was kidney injury in patients with type II diabetes after contracting COVID-19. The protocol for this study was published on PROSPERO (registration number CRD42023413887). Results: Initially, 6,339 articles were included in the search, from which only 6 observational studies were selected by following the 2020 PRISMA statement. The quality of the evidence was assessed by a tool provided by the National Institutes of Health (observational studies). The total number of participants included in the studies was 14,723. Our systematic literature review and meta-analysis provide compelling evidence that kidney injury is a prevalent complication of COVID-19 infection in the type II diabetes population, with a pooled odds ratio of 2.27 (95% CI: 2.05–2.51; p < 0.00001), often necessitating hospitalization and hemodialysis in severe cases. Conclusion: Covid-19 is associated with a two-fold increase in nephropathy and acute kidney injury in diabetes mellitus type 2 patients compared to non-diabetic patients. This implies that kidney injury is more likely to occur in diabetes mellitus type 2 patients post Covid infection. [ABSTRACT FROM AUTHOR]

Background: During diabetes, prorenin is highly produced by the renal collecting ducts. The binding of prorenin to (pro)renin receptor (PRR) on the apical plasma membrane triggers intracellular profibrotic genes, including TGF-β and CTGF. However, the underlying mechanisms contributing to the stimulation of these pathways remain unclear. Hence, we hypothesize that the glucose transporter-1 (GLUT1) favors the PRR-dependent stimulation of TGF-β and CTGF in the distal nephron segments during high glucose (HG) conditions. Methods: To test this hypothesis, primary cultured renal inner medullary collecting duct (IMCD) cells were treated with normal glucose (NG, 5 mM) or high glucose (HG, 25 mM) for 48 h in the presence or absence of the GLUT1-specific inhibitor BAY 876 (2 nM). Additionally, IMCD cells were treated with the PRR antagonist PRO20. The expression of TGF-β and CTGF was quantified by immunoblot and qRT-PCR. Results: HG increased GLUT1 mRNA and protein abundance, while BAY 876 inhibited these responses. HG treatment upregulated PRR, but the concomitant treatment with BAY 876 partially prevented this effect. TGF-β and CTGF expressions were augmented in IMCD cells treated with HG. However, PRO20 prevented the increases in TGF-β but not those of CTGF. GLUT1 inhibition partially prevented the increases in reactive oxygen species (ROS) during HG while PRO20 did not. ROS scavenging impaired CTGF upregulation during HG conditions. Additionally, long-term exposure to HG increases lipid peroxidation and reduced cell viability. Conclusions: The data indicate that glucose transportation via GLUT1 is implicated in the PRR-dependent upregulation of TGF-β while CTGF is mediated mainly via a mechanism depending on ROS formation in renal medullary collecting duct cells. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases, including Alzheimer's Disease (AD) and Parkinson's Disease (PD) are common complications of diabetes, arising from insulin resistance, inflammation, and other pathological processes in the central nervous system. The potential of numerous antidiabetic agents to modify neurodegenerative disease progression, both preclinically and clinically, has been assessed. These agents may provide additional therapeutic benefits beyond glycemic control. Introduced in the twenty-first century, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a class of antidiabetic drugs noted not only for their potent glucose-lowering effects but also for their cardiovascular and renal protective benefits. Various GLP-1RAs have been demonstrated to have significant benefits in in vitro and in vivo models of neurodegenerative diseases through modulating a variety of pathogenic mechanisms, including neuroinflammation, autophagy, mitochondrial dysfunction, and the abnormal phosphorylation of pathognomonic proteins. These agents also have substantial protective effects on cognitive and behavioral functions, such as motor function. However, clinical trials investigating GLP-1RAs in diseases such as AD, PD, mild cognitive impairment, psychiatric disorders, and diabetes have yielded mixed results for cognitive and motor function. This review examines the link between diabetes and neurodegenerative diseases, explores the effects of antidiabetic agents on neurodegeneration, provides a concise overview of the GLP-1 pathway, and discusses both preclinical and clinical trial outcomes of GLP-1RAs for neurodegenerative diseases, including their effects on cognition in AD and PD. This review also proposed new strategies for the design of future clinical trials on GLP-1 RAs for both AD and PD. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) has emerged as a notable public health issue in China due to the aging population and rapid urbanization. This study aimed to describe the characteristics of patients with AF (paroxysmal and nonparoxysmal) and investigate the association between left ventricular ejection fraction (LVEF) levels and AF subtypes to facilitate early prevention in patients with AF. Method: Patients with AF who presented at the cardiology department of the First People's Hospital of Yancheng were recruited in this study. In univariate and multivariate logistic regression analyses, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the relationships between each dependent variable and nonparoxysmal AF. The restricted cubic splines (RCS) curve was employed to explore the linear relationship between LVEF and nonparoxysmal AF on a continuous scale. Subgroup analysis was applied to examine the stability of the results. Results: The study included a total of 2054 patients who were diagnosed with AF. 652 (31.74%) patients had paroxysmal AF, and 1402 (68.26%) had nonparoxysmal AF. Multivariate logistic regression analyses indicated that compared to those with paroxysmal AF, patients with nonparoxysmal AF tended to have a higher prevalence of coronary artery disease, lower levels of LVEF, and an elevated heart rate. Additionally, RCS curves also showed that LVEF was negatively and linearly associated with the nonparoxysmal AF. Furthermore, the association between LVEF and nonparoxysmal AF was stronger among patients with hypertension and obesity (P for interaction < 0.05). Conclusions: Patients with nonparoxysmal AF have a more advanced AF burden and the transition from paroxysmal to nonparoxysmal AF should be recognized in time, especially to treat the corresponding comorbidities (including hypertension and obesity) more consistently. [ABSTRACT FROM AUTHOR]

Background: Insomnia symptoms that influence daytime functioning are common among adults with type 2 diabetes. However, no previous study has examined if levels of physical activity differ among adults with diabetes with and without insomnia symptoms. Thus, the aim of this study was to assess the difference in total physical activity (TPA) and moderate-to-vigorous physical activity (MVPA) levels in individuals with diabetes with and without insomnia symptoms. Methods: This cross-sectional study included 1,354 participants with any type of diabetes who participated in the Norwegian HUNT4 Study, 2017-19. Participants were defined to have 'insomnia symptoms' if they reported difficulty initiating and/or maintaining sleep ≥ 3 nights/week during the last 3 months. MVPA (defined as moderate/brisk walking [> 4.0 km/h], running, and cycling), and TPA (MVPA including slow walking [≤ 4.0 km/h]) were determined from two accelerometers worn on the thigh and lower back. Analyses were stratified by age and sex. Results: The median age was 67 years and 491 (36%) had insomnia symptoms and 37 (3%) had insomnia disorder. Among women, 28% with one or more insomnia symptoms fulfilled the recommended minimum level of physical activity, as compared to 34% in women without insomnia symptoms. The corresponding proportions in men were 48% and 45%. Women above 65 years with insomnia symptoms performed less TPA (-73 min/week, 95% CI -122 to -24) and MVPA (-33 min/week, 95% CI -50 to -15), compared to women without insomnia symptoms in the same age group. There was no clear difference in physical activity levels according to insomnia symptoms in men or women below 65 years. Women and men with insomnia disorder had substantially lower TPA (women: -192 min/week, 95% CI -278 to -106; men: -276 min/week, 95% CI -369 to -193) and MVPA (women: -37 min/week, 95% CI -63 to -11; men: -67 min/week, 95% CI -83 to -50) than those without insomnia symptoms. Conclusions: This study showed that women above 65 years with insomnia symptoms and individuals with insomnia disorder performed less physical activity, suggesting that these subgroups may suffer from additional challenges that prevent them from engaging in regular physical activity. [ABSTRACT FROM AUTHOR]

Background: The double-blind, 2 × 2 factorial design, placebo-controlled ASCEND randomized trial compared the effects of 100 mg aspirin daily and, separately, 1 g omega-3 fatty acids (FAs) daily on the primary prevention of cardiovascular disease in 15,480 UK adults with diabetes. We report the effects of these randomized treatment allocations on scores derived from the National Eye Institute's Visual Function Questionnaire-25 (NEI-VFQ-25) in a subset of participants involved in the ASCEND-Eye sub-study. Methods: Ordinal data from the NEI-VFQ-25 were analyzed using proportional odds regression methods. A common odds ratio with a 95% confidence interval was used to interpret the average effect size of randomization to each study treatment on composite and subdomain scores from the questionnaire. Results: Neither randomization to aspirin nor omega-3 FAs for 7.5 years significantly affected composite or subdomain scores from the NEI-VFQ-25. Conclusion: Applying the NEI-VFQ-25 in ASCEND-Eye represents one of the largest surveys of vision-targeted health-related quality of life in people with diabetes. Further observational analyses of these data are planned, to identify the clinical and demographic characteristics associated with lower composite and subdomain scores in a diabetic population. Trial registration: Eudract No. 2004–000991-15; Multicentre Research Ethics Committee Ref No. 03/8/087 (29th December 2003); ClinicalTrials.gov No. NCT00135226 (24th August 2005); ISRCTN No. ISRCTN60635500 (1st September 2005). [ABSTRACT FROM AUTHOR]

Objective: The study aims to investigate the associations of triglyceride glucose (TyG), TyG combined with body mass index (TyG-BMI), metabolic score for insulin resistance (METS-IR), the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), and the risk of mild cognitive impairment (MCI) in individuals without diabetes aged 45 and above. Methods: The most recent data in this study were from a cohort study, which sourced samples from the China Health and Retirement Longitudinal Study, spanning 2011 to 2018. The four indices' associations with MCI risk were analyzed using logistic regression. The predictive capacity was measured using the receiver operating characteristic (ROC) curve. Results: Over a 7-year follow-up, 1,261 individuals (31.34%) of the 4,027 participants developed MCI. Logistic regression analysis revealed significant associations between these surrogate indices and MCI. The findings for the highest quartile compared with the lowest quartile were as follows: TyG: 1.24 (95% CI: 1.02, 1.49); TyG-BMI: 1.38 (95% CI: 1.13, 1.68); METS-IR: 1.50 (95% CI: 1.09, 2.06); TG/HDL-C: 1.34 (95% CI: 1.10, 1.64). ROC analysis revealed that TyG, TyG-BMI, TG/HDL-C, and METS-IR demonstrated excellent discriminatory power for MCI, with area under the curve (AUC) values of 0.82 (95% CI: 0.80, 0.83), 0.82 (95% CI: 0.80, 0.83), 0.83 (95% CI: 0.80, 0.84), and 0.83 (95% CI: 0.80, 0.84), respectively. The four indices showed stronger ability to predict MCI risk in females compared to males. Conclusion: Elevated levels of four indices are positively correlated with MCI risk. TyG-BMI and METS-IR demonstrate stronger capabilities in identifying MCI across both male and female populations. This suggests that early intervention in patients with elevated IR surrogate indices may help reduce the MCI. [ABSTRACT FROM AUTHOR]

Background: Both anti-aging protein α-Klotho and the triglyceride-glucose (TyG) index hold predictive value for the incidence, progression, and outcomes of cardiovascular disease, diabetes and many other diseases. However, their relationship remains unclear. Methods: We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2016. Weighted multivariate linear regression models and subgroup analysis were constructed to assess the association between TyG index and α-Klotho levels. Nonlinear correlations were explored using restricted cubic splines (RCS), generalized additive models (GAM) and smooth curve fitting. Segmented regression model was conducted to explore potential threshold effects and identify the inflection point. Results: A total of 2568 participants satisfied the predetermined criteria were enrolled in the final analysis. After fully adjusting for covariates, TyG index was shown to be markedly negatively correlated with α-Klotho [β=-74.07, 95%CI (-100.29,-47.85), p < 0.001]. Gender was significantly correlated with this negative connection according to subgroup analysis and interaction testing (p for interaction < 0.05).Additionally, we discovered a linear association between TyG index and α-Klotho in all participants (p for nonlinear = 0.761), while non-linear association in female (p for nonlinear = 0.016).The analysis of threshold effect in the female participants found that the inflection point of TyG index was 8.01, exceed which the level of α-Klotho decreased significantly with increasing TyG index[β=-151.72, 95%CI (-201.93, -101.50), p < 0.001]. Conclusion: Our findings demonstrate a negative association between TyG index and α-Klotho levels, with the effect being more pronounced in females. TyG index may serve as an early indicator of individuals with low α-Klotho levels, especially among females. These findings highlight the need for gender-specific considerations in clinical interventions to improve public health. Further research is needed to clarify the causal direction of this association. [ABSTRACT FROM AUTHOR]

Background: Post-transplant diabetes mellitus (PTDM) is a well-known complication of kidney transplantation that significantly impacts recipient morbidity and mortality. Over the recent years, the incidence of PTDM has increased considerably worldwide. Therefore, the primary purpose of this study was to evaluate the incidence and risk factors for PTDM in living donor kidney transplantation patients in Riyadh, Saudi Arabia. Methods: A retrospective cohort study was conducted at a tertiary transplant center in Riyadh, Saudi Arabia, and data were extracted between February 2016 and March 2022. Patients aged ≥ 18 years who underwent renal transplant with at least one year of post-transplant follow-up were included in the analysis, and their medical records were comprehensively reviewed. Patients < 18 years of age, history of diabetes mellitus, other organ transplants, or those who underwent transplantation outside the Kingdom of Saudi Arabia were excluded from the study. Results: The study included 247 living donor kidney transplant patients, with a mean age of 39.5 ± 14.6 years. 17.0% of the patients were diagnosed with PTDM. Patient age and fasting glucose levels at 6-months and 12-months after transplantation were found to be significant risk factors for the development of PTDM. Conclusion: An increased occurrence of PTDM emphasizes the importance of identifying high-risk patients prior to transplantation and implementing early interventions to prevent potential complications that could affect graft and patient survival. [ABSTRACT FROM AUTHOR]

Introduction: Considering that the adoption of self-care behaviors in patients with type 2 diabetes can reduce the complications caused by this disease, aim of the present study was compared the effect of SMS-based teaching and face-to-face teaching on self-care behavior of type 2 diabetic patients in Khorramabad city. Methods: This was a pre- and post-test semi-experimental study. The research sample size was composed of 135 diabetic patients referred to the Khorramabad diabetes clinic who were selected using random sampling method and were randomly divided into face-to-face teaching group (n = 45), SMS-based teaching group (n = 45), and control (n = 45). Data collection tools were demographic information questionnaire, Tubert self-care behaviours questionnaire, and self-efficacy questionnaire. The educational intervention in the face-to-face training group included four face-to-face training sessions and in the SMS-based training group included three to four daily training SMS and without training intervention in the control group. For all analysis, SPSS software version 24 was done and at a significance level of 0.05. Results: At the baseline, average score of self-efficacy and self-care, and blood sugar were not significant between the face-to-face teaching, SMS-based and control groups. However, at the end of intervention, the mean score of these variables were significantly more in the face-to-face teaching and SMS-based groups compared to the control group (p-value < 0.001). Discussion: Considering the positive effect of educational intervention in promoting self-care in patients with type 2 diabetic, it is suggested to use empowerment programs with self-care approach to improve the health of diabetic patients. [ABSTRACT FROM AUTHOR]

Background: We aimed to develop risk tools for dementia, stroke, myocardial infarction (MI), and diabetes, for adults aged ≥ 65 years using shared risk factors. Methods: Data were obtained from 10 population-based cohorts (N = 41,755) with median follow-up time (years) for dementia, stroke, MI, and diabetes of 6.2, 7.0, 6.8, and 7.4, respectively. Disease-free participants at baseline were included, and 22 risk factors (sociodemographic, medical, lifestyle, laboratory biomarkers) were evaluated. Two risk tools (DemNCD and DemNCD-LR based on Fine and Gray sub-distribution and logistic regression [LR], respectively) were developed and validated. Predictive accuracies of these risk tools were assessed using Harrel's C-statistics and area under the curve (AUC) and 95% confidence interval (CI). Model calibration was conducted using Hosmer–Lemeshow goodness of fit test along calibration plots. Results: Both the DemNCD and DemNCD-LR resulted in similar predictive accuracy for each outcome. The overall AUC (95% CI) for dementia, stroke, MI, and diabetes risk tool were 0·68 (0·65, 0·70), 0·58 (0·54, 0·61), 0·65 (0·61, 0·68), and 0·68 (0·64, 0·72), respectively, for males. For females, these figures were 0·65 (0·63, 0·67), 0·55 (0·52, 0·57), 0·65 (0·62, 0·68), and 0·61 (0·57, 0·65). Conclusions: The DemNCD is the first tool to predict both dementia and multiple cardio-metabolic diseases using comprehensive risk factors and provided similar predictive accuracy to existing risk tools. It has similar predictive accuracy as tools designed for single outcomes in this age-group. DemNCD has the potential to be used in community and clinical settings as it includes self-reported and routinely available clinical measures. [ABSTRACT FROM AUTHOR]

Introduction: Depression and alcohol use disorder (AUD) in people living with Type 2 diabetes mellitus (T2DM) are associated with worse health outcomes. AUD is strongly associated with depression and anxiety, but it is not known how these conditions cluster in people with T2DM. We investigated rates of new episodes of depression and anxiety following T2DM diagnosis in people with and without prior AUD among an English primary care population. Methods: The study population was people diagnosed with T2DM between 2004 and 2019. We used the Clinical Practice Research Datalink (CPRD) Aurum database and linked Hospital Episode Statistics Admitted Patient Care (HES APC) and Office for National Statistics (ONS) mortality data. We examined incidence of new episodes of anxiety or depression in people with T2DM with and without AUD. AUD was defined as any of i) clinical diagnosis; ii) alcohol withdrawal; or iii) chronic alcohol-related harm (physical or mental) using SNOMED-CT or ICD-10 codes. People were excluded if they had codes for depression/anxiety 12 months prior to T2DM diagnosis. Poisson regression models were fitted adjusting sequentially for a) age, gender, calendar time; b) region, Index of Multiple Deprivation, ethnicity, body mass index, smoking status, Charlson co-morbidity index; and c) history of a mental health condition. Results: Our study population was 479,447 people of whom 10,983 (2.3%) had an AUD code prior to T2DM diagnosis. After adjusting for all measured confounders except history of a mental health condition, IRR for depression was 2.00 (95% CI 1.93, 2.06) for people with AUD compared to without AUD. This reduced to 1.45 (95% CI 1.41, 1.50) after further adjustment for history of a mental health condition. Findings for anxiety were substantially similar to those for depression (adjusted for all measured confounders except history of a mental health condition, IRR 2.08 95% CI 1.99, 2.18 fully adjusted IRR 1.48 95% CI 1.41, 1.55). Conclusions: People with AUD have over double the rates of depression and anxiety following T2DM diagnosis than those without AUD. This was only partially explained by pre-existing diagnoses of mental health conditions. A holistic approach incorporating mental health support is needed to improve health outcomes for people with AUD who develop T2DM. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a major public health concern with significant cardiovascular complications (CVD). Despite extensive epidemiological data, the molecular mechanisms relating hyperglycemia to CVD remain incompletely understood. We here investigated the impact of chronic hyperglycemia on human aortic smooth muscle cells (HASMCs) cultured under varying glucose conditions in vitro, mimicking normal (5 mmol/L), pre-diabetic (10 mmol/L), and diabetic (20 mmol/L) conditions, respectively. Normal HASMC cultures served as baseline controls, and patient-derived T2DM-SMCs served as disease controls. Results showed significant increases in cellular proliferation, area, perimeter, and F-actin expression with increasing glucose concentration (p < 0.01), albeit not exceeding the levels in T2DM cells. Atomic force microscopy analysis revealed significant decreases in Young's moduli, membrane tether forces, membrane tension, and surface adhesion in SMCs at higher glucose levels (p < 0.001), with T2DM-SMCs being the lowest among all the cases (p < 0.001). T2DM-SMCs exhibited elevated levels of selected pro-inflammatory markers (e.g., ILs-6, 8, 23; MCP-1; M-CSF; MMPs-1, 2, 3) compared to glucose-treated SMCs (p < 0.01). Conversely, growth factors (e.g., VEGF-A, PDGF-AA, TGF-β1) were higher in SMCs exposed to high glucose levels but lower in T2DM-SMCs (p < 0.01). Pathway enrichment analysis showed significant increases in the expression of inflammatory cytokine-associated pathways, especially involving IL-10, IL-4 and IL-13 signaling in genes that are up-regulated by elevated glucose levels. Differentially regulated gene analysis showed that compared to SMCs receiving normal glucose, 513 genes were upregulated and 590 genes were downregulated in T2DM-SMCs; fewer genes were differentially expressed in SMCs receiving higher glucose levels. Finally, the altered levels in genes involved in ECM organization, elastic fiber synthesis and formation, laminin interactions, and ECM proteoglycans were identified. Growing literature suggests that phenotypic switching in SMCs lead to arterial wall remodeling (e.g., change in stiffness, calcific deposits formation), with direct implications in the onset of CVD complications. Our results suggest that chronic hyperglycemia is one such factor that leads to morphological, biomechanical, and functional alterations in vascular SMCs, potentially contributing to the pathogenesis of T2DM-associated arterial remodeling. The observed differences in gene expression patterns between in vitro hyperglycemic models and patient-derived T2DM-SMCs highlight the complexity of T2DM pathophysiology and underline the need for further studies. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM), a chronic metabolic disease, poses a significant global health challenge, with current treatments often fail to prevent the long-term disease complications. Mesenchymal stem/stromal cells (MSCs) are, adult progenitors, able to repair injured tissues, exhibiting regenerative effects and immunoregulatory and anti-inflammatory responses, so they have been emerged as a promising therapeutic approach in many immune-related and inflammatory diseases. This review summarizes the therapeutic mechanisms and outcomes of MSCs, derived from different human tissue sources (hMSCs), in the context of DM type 1 and type 2. Animal model studies and clinical trials indicate that hMSCs can facilitate pleiotropic actions in the diabetic milieu for improved metabolic indices. In addition to modulating abnormally active immune system, hMSCs can ameliorate peripheral insulin resistance, halt beta-cell destruction, preserve residual beta-cell mass, promote beta-cell regeneration and insulin production, support islet grafts, and correct lipid metabolism. Moreover, hMSC-free derivatives, importantly extracellular vesicles, have shown potent experimental anti-diabetic efficacy. Moreover, the review discusses the diverse priming strategies that are introduced to enhance the preclinical anti-diabetic actions of hMSCs. Such strategies are recommended to restore the characteristics and functions of MSCs isolated from patients with DM for autologous implications. Finally, limitations and merits for the wide spread clinical applications of MSCs in DM such as the challenge of autologous versus allogeneic MSCs, the optimal MSC tissue source and administration route, the necessity of larger clinical trials for longer evaluation duration to assess safety concerns, are briefly presented. [ABSTRACT FROM AUTHOR]

Background: Central obesity is a well-recognized risk factor for diabetes, yet the potential role of lipids in the diabetes risk associated with central obesity remains unclear. This study aimed to explore the possible mediating role of 11 lipid parameters [high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), non-high-density lipoprotein cholesterol (Non-HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), remnant cholesterol (RC), and ratios of Non-HDL-C/HDL-C, RC/HDL-C, LDL/HDL-C, TG/HDL-C, TC/HDL-C] in the association of central obesity with diabetes risk. Methods: We utilized data from 15,453 participants in the NAGALA longitudinal cohort to assess the association of baseline central obesity indicators [waist-height ratio (WHtR), waist circumference (WC)] and the 11 lipid parameters with diabetes risk. Mediation analysis models were constructed to explore the mediating role of lipid parameters in the association of WC/WHtR with diabetes. Results: Confirmatory associative analysis using multivariable Cox regression showed that, except for Non-HDL-C, TC and LD-C, the remaining eight lipid parameters were significantly associated with WC/WHtR and diabetes risk. Mediation analysis indicated that TG, RC, HDL-C, and lipid ratios such as Non-HDL-C/HDL-C ratio, RC/HDL-C ratio, TG/HDL-C ratio, TC/HDL-C ratio and LDL/HDL-C ratio are potential lipids affecting the diabetes risk related to central obesity. Among these, the RC/HDL-C ratio seemed to contribute the most in the WC/WHtR-related diabetes risk association, with a mediation percentage of about 37%. Additionally, lipid ratio parameters appeared to play a more mediating role in the association of central obesity-related diabetes risk than individual lipids. Conclusions: In central obesity-related diabetes risk, most lipids, especially lipid ratio parameters, play a significant mediating role. Given these findings, we advocate for increased efforts in multifactorial risk monitoring and joint management of diabetes. The evaluation of lipids, particularly lipid ratio parameters, may be holds substantial value in the prevention and management of diabetes risk under close monitoring of central obesity. [ABSTRACT FROM AUTHOR]

Background: Atherosclerotic cardiovascular diseases remain the leading cause of mortality in diabetic patients, with endothelial cell (EC) dysfunction serving as the initiating step of atherosclerosis, which is exacerbated in diabetes. Krüppel-like factor 11 (KLF11), known for its missense mutations leading to the development of diabetes in humans, has also been identified as a novel protector of vascular homeostasis. However, its role in diabetic atherosclerosis remains unexplored. Methods: Diabetic atherosclerosis was induced in both EC-specific KLF11 transgenic and knockout mice in the Ldlr−/− background by feeding a diabetogenic diet with cholesterol (DDC). Single-cell RNA sequencing (scRNA-seq) was utilized to profile EC dysfunction in diabetic atherosclerosis. Additionally, gain- and loss-of-function experiments were conducted to investigate the role of KLF11 in hyperglycemia-induced endothelial cell dysfunction. Results: We found that endothelial KLF11 deficiency significantly accelerates atherogenesis under diabetic conditions, whereas KLF11 overexpression remarkably inhibits it. scRNA-seq profiling demonstrates that loss of KLF11 increases endothelial-to-mesenchymal transition (EndMT) during atherogenesis under diabetic conditions. Utilizing gain- and loss-of-function approaches, our in vitro study reveals that KLF11 significantly inhibits EC inflammatory activation and TXNIP-induced EC oxidative stress, as well as Notch1/Snail-mediated EndMT under high glucose exposure. Conclusion: Our study demonstrates that endothelial KLF11 is an endogenous protective factor against diabetic atherosclerosis. These findings indicate that manipulating KLF11 could be a promising approach for developing novel therapies for diabetes-related cardiovascular complications. [ABSTRACT FROM AUTHOR]

Background: Estimation of global diabetes burden in adolescents and young adults (10–24 years) from 1990 to 2021. Methods: Data were extracted from the 2021 Global Burden of Disease Study. Joinpoint regression analysis was employed to examine trends over the past 30 years, frontier analysis identified regions with potential for improvement, and the slope index of inequality and the relative concentration index were used to assess health inequalities. Results: From 1990 to 2021, the age-standardized prevalence rates (ASPR) and age-standardized disability-adjusted life years rates (ASDR) of diabetes in adolescents and young adults increased globally, while age-standardized death rates (ASMR) remained stable. Oceania bore the highest burden regionally, East Asia experienced the fastest rise in ASPR and ASDR, and High-income Asia Pacific saw the most significant decrease in ASMR. Among 204 countries, Marshall Island and Hait reported the highest ASPR, ASDR, and ASMR in 2021. Health inequality analysis confirmed that the burden was concentrated in countries with lower Socio-Demographic Index (SDI). Frontier analysis showed that ASMR and ASDR were negatively correlated with SDI, with Yemen and Honduras, which have lower socio-demographic indices, exhibiting more smaller overall differences from frontier boundaries. Conclusions: The analysis revealed a sharp increase in the global ASPR and ASDR of diabetes in adolescents and young adults. Additionally, the disease burden is typically concentrated in countries with lower SDI, highlighting an urgent need for governments to develop flexible health policies to mitigate the escalating threat of diabetes in this demographic. [ABSTRACT FROM AUTHOR]

One of the most common health concerns disturbing people within working years globally is diabetes mellitus (DM). One well-known consequence of DM is vascular damage, which can manifest as macro- and microangiopathy affecting the ocular retina. Therefore, Diabetic macular edema (DME) is a major sight-threatening complication of diabetic retinopathy (DR) worldwide. It is the most prevalent cause of significant vision impairment in diabetic patients. Long-term vision loss can be avoided by following early DME treatment guidelines in everyday life. Hence, there are various therapeutic approaches for DME management. Currently, the first-line treatment for DME is anti-VEGF family drugs, such as ranibizumab, brolucizumab, bevacizumab, and aflibercept. Nevertheless, relapses of the disease, inadequate response, and resistance during anti-VEGF therapy are still seen because of the intricate pathophysiological foundation of the disease. Consequently, there is an excellent requirement for therapeutic approaches to advance and become better at controlling diseases more satisfactorily and require fewer treatments overall. We conducted a thorough literature search in the current review to present a comprehensive overview of the primary data about the current DME therapeutic agents. We also covered the novel advances in DME management and probable future treatments being investigated and developed. This review recommended that Large clinical trials should afford sufficient evidence to support these innovative treatment modalities. [ABSTRACT FROM AUTHOR]

Background: One in six Mexican adults' lives with type 2 diabetes mellitus (T2DM), which is the third leading cause of death in the country. Analyzing the geographic distribution of T2DM mortality helps identify regions with higher mortality rates. This study aimed to examine the spatial patterns of mortality from type 2 diabetes mellitus (T2DM) across municipalities in Mexico and to analyze the main contextual factors linked to this cause of death in 2020. Methods: We employed a spatial Bayesian hierarchical regression model to estimate the risk and probability of death from type 2 diabetes mellitus (T2DM) across Mexico's municipalities. Results: The SMR results revealed geographic and age-specific patterns. Central Mexico and the Yucatán Peninsula exhibited the highest excess mortality rates. For the population under 50 years of age, municipalities in Oaxaca had the highest T2DM mortality rates, whereas those aged 50 years old and older had the highest rates in Tlaxcala and Puebla. Socioeconomic factors such as low levels of educational attainment, lack of health services, dietary deficiency, and marginalization were positively associated with increased T2DM mortality risk. By contrast, GDP per capita showed a negative association. High-risk areas for T2DM mortality were prominent along the south of the Pacific Coast, the Bajío, Central Mexico, and southern Yucatán for those under 50, and along a central strip extending to the Yucatán Peninsula for the older population. Significant uncertainties in mortality risk were identified, with Central Mexico, Oaxaca, Chiapas, and Tabasco showing high probabilities of excess risk for those under 50 years of age and extended risk areas along the Gulf of Mexico for those 50 years old and older. Conclusions: The assessment and identification of spatial distribution patterns associated with T2DM mortality, and its main contextual factors, are crucial for informing effective public health policies aimed at reducing the impact of this chronic disease in Mexico. [ABSTRACT FROM AUTHOR]

Background: Emphysematous pyelonephritis is a rare and severe urinary tract infection that is potentially life-threatening and easily progresses to septic shock. In this report, we present a unique case of emphysematous pyelonephritis caused by Raoultella ornithinolytica. Case presentation: An 86-year-old man presented with severe back pain of 3 days' duration. He had a history of hypertension and diabetes for more than 20 years, and his infection indicators and serum creatinine were elevated. Abdominal computed tomography revealed an abnormal gas shadow around his right kidney and the anterior edge of his right psoas muscle. Consequently, he was initially diagnosed with emphysematous pyelonephritis. There was no evidence of nephrolithiasis or other anatomical or structural abnormalities that could have precipitated this focal renal infection. Both blood and drainage fluid cultures revealed R. ornithinolytica. After early anti-infection treatment, percutaneous drainage and moderate control of blood glucose, the patient gradually recovered. Conclusions: Emphysematous pyelonephritis caused by R. ornithinolytica is rare but has a high drug resistance rate potentially and may cause severe infections. Early diagnosis, prompt use of antibiotics that are sensitive to the organism, and decompression drainage could be the key to treatment. [ABSTRACT FROM AUTHOR]

Objective: The COVID-19 pandemic restrictions have substantially affected people's health and rapidly changed their daily routines. This is a prospective study that investigated the impact of the pandemic on primary school children with Type 1 diabetes and their parents during the first lockdown in Kuwait. Methods: A questionnaire battery related to mental health, well-being, and lifestyle was administered at baseline in Summer 2019 (face-to-face, at a diabetes outpatient clinic) and at follow-up during lockdown in Summer 2020 (via telephone, in adherence with COVID-19 restrictions). Data were collected for 70 dyads with children aged 9–12 years. Results: Significant differences were found in most scores for both children and parents. Their mental health worsened to a higher level of depression, anxiety, stress, and a poor level of wellbeing. The average scores on the follow-up tests fell within a clinical range on these measures. Significant differences in their lifestyle, compared to before the lockdown, included decreased levels of physical activity and lower healthy core nutritional intake. Conclusions: Our findings indicate that the COVID-19 lockdown has had a significant psychological and possibly physiological impact on children with Type 1 diabetes and their parents. We conclude that there is a need for mental health support services focusing on these groups. Although full lockdown restrictions will have stopped in the past year, post-pandemic stressors may be expected to continue to adversely affect this cohort. [ABSTRACT FROM AUTHOR]

Background: South Africa is experiencing a persistent growth in non-communicable diseases. Diabetes is among the top ten causes of mortality, especially among women, which is partly driven by high levels of added sugar consumption and obesity. To reduce obesity rates and the incidence of diabetes, South Africa introduced a tax on sugar sweetened beverages (also known as the Health Promotion Levy (HPL)) in 2018. The tax is applicable to sugar-sweetened beverages but excludes 100% fruit juice. The government is currently considering extending the tax to include fruit juices. This study models the potential health and economic impact of taxing fruit juices at 20% of the retail price of one liter. Methods: To analyze the distributional impact of the tax, this study uses extended cost-effectiveness analysis methodology. Data on price elasticities, healthcare cost, income, fruit juice consumption were sourced from the literature and representative national surveys. The potential impact of the tax on diabetes incidence, prevalence, mortality, and financial benefits were estimated for each income group (lowest, quintile 1 to highest, quintile 5). Findings: We estimate that a 20% tax on fruit juice would avert 156,640 incident cases of type 2 diabetes mellitus over 20 years, with most disease averted occurring among the first- and fifth-income groups. Averted deaths from diabetes would average 2,000 deaths per quintile (for quintiles 1 to 4) and about 2,800 in quintile 5. The improved health resulting from averted incidence and deaths will reduce overall healthcare expenditure by R7.5 billion over 20 years, of which R2.3 billion will occur in the fifth quintile. The South African government will also save about R300 million in subsidizing diabetes-related healthcare cost as a result of prevention; and would raise R8.6 billion in tax revenues per annum. Out-of-pocket expenditure savings will be R303 million and a financial risk protection (money-metric value of insurance) of R4.6 billion over the 20-year period. Conclusion: We conclude that an HPL that significantly raises the retail price of fruit juices would reduce consumption and diabetes-related morbidity and mortality. The tax will also provide significant financial benefits in the form of reduced healthcare costs for both government and households as well as providing financial risk protection to individuals. Health taxes are win-win policies that improve population health and generate revenue for governments to fund public health services delivery and thus improve overall health financing activities of the government. Therefore, population level disease prevention measures such as health taxes are important for achieving universal health coverage. [ABSTRACT FROM AUTHOR]

Background: Relationship between dysphagia and dehydration has not been studied widely. The aim of this study is to determine the frequency of dysphagia and dehydration in geriatric outpatient clinic, to evaluate the relationship between these two conditions. Methods: The cross-sectional study included 1345 patients. Plasma osmolarity (Posm) was calculated using the following formula: [1.86 x (Na + K) + 1.15 x glucose + urea + 14]. Overt dehydration was defined as a calculated Posm of > 300 mmol/L. Eating Assessment Tool (EAT-10) score of ≥ 3 was accepted as dysphagia. Associations between dehydration and dysphagia was evaluated. Results: Mean age was 78 ± 8 years, and 71% were females. Dysphagia was observed in 27% of patients. Dysphagia was associated with a higher number of drug exposure, dependency on basic activities of daily living and geriatric depression (p < 0.05). Overt dehydration was found in 29% of patients with dysphagia, and 21% of patients with no dysphagia (p = 0.002); and dysphagia was significantly associated with overt dehydration mmol/L (OR 1.49, 95% CI 1.13–1.96, p = 0.005) after adjustments for age and sex. In another model, EAT-10 score was found as one of the independent predictors of overt dehydration (OR1.03, 95% CI 1.00-1.06, p = 0.38), along with diabetes mellitus (OR 2.32, 95% CI 1.72–3.15, p < 0.001), chronic kidney disease (OR 3.05, 95% CI 2.24–4.15, p < 0.001), and MNA score (OR 0.97, 95% CI 0.94-1.00, p = 0.031). Conclusion: EAT-10 scale was independently associated with overt dehydration among older adults, as MNA score was. Correction of both dysphagia and malnutrition might improve overt dehydration to a better extent than correction either of these factors alone. Future studies are needed to test cause and effect relationships. [ABSTRACT FROM AUTHOR]

Background : Biomedical and lifestyle factors in Western populations have significantly shifted in recent decades, influencing public health and contributing to the increasing prevalence of non-communicable diseases (NCDs) that share inflammation as common pathology. Methods: We investigated the relationship between these factors and 11 NCDs in the cross-sectional FoCus cohort (n = 1220), using logistic regression models. Associations with age-at-disease-onset were specifically analyzed for type 2 diabetes (T2D, low-grade chronic inflammation) and inflammatory bowel disease (IBD, high-grade chronic inflammation) in disease-specific cohorts (FoCus-T2D, n = 514; IBD-KC, n = 1110). Important factors for disease risk were identified using Cox-PH-regression models and time-to-event analysis. We further explored the interaction between identified risk factors and gut microbiome composition using linear models. Results: Lifestyle factors were clearly linked to disease phenotypes, particularly in T2D and IBD. Still, some factors affected only the age-at-onset, but not disease prevalence. High-quality nutrition significantly delayed onset for both IBD and T2D (IBD: HR = 0.81 [0.66; 0.98]; T2D: HR = 0.45 [0.28; 0.72]). Smoking accelerated T2D onset (HR = 1.82 [1.25; 2.65]) but delayed onset in ulcerative colitis (UC: HR = 0.47 [0.28; 0.79]). Higher microbiota diversity delayed IBD onset (Shannon: HR = 0.58 [0.49; 0.71]) but had no effect on T2D. The abundance of specific microbial genera was strongly associated with various biomedical and lifestyle factors in T2D and IBD. In unaffected controls, these effects were smaller or reversed, potentially indicating a greater susceptibility of the gut microbiome to negative influences in T2D and IBD. Conclusions: The dual insights into age-at-disease-onset and gut microbiota composition in disease emphasize the role of certain biomedical and lifestyle factors, e.g., nutrition quality, in disease prevention and management. Understanding these relationships provides a foundation for developing targeted strategies to mitigate the impact of metabolic and inflammatory diseases through lifestyle modifications and gut health management. [ABSTRACT FROM AUTHOR]

Background: Hypertension and type 2 diabetes mellitus (T2DM) are important contributors to noncommunicable disease related morbidity and mortality. Health systems could benefit from exploring the use of Faith-Based Centres (FBC) to screen and link suspected cases for further care in order to help achieve Sustainable Development Goal (SDG) 3. The study investigated the role of faith-based screening for T2DM and hypertension and the linkage of cases to the healthcare system and examined the care cascade in the Kassena Nankana Districts of Northern Ghana. Methods: We screened individuals from 6 FBCs for elevated blood pressure and hyperglycaemia. Suspected hypertension and T2DM cases were referred to health facilities for confirmation and subsequently followed them up for 3 months. We assessed the prevalence of behavioural and metabolic risk factors, including hypertension and T2DM, and the retention of referred cases in the healthcare system over follow up period. We further assessed levels of awareness, treatment and adequate control of hypertension and T2DM. Results: A total of 631 participants were screened, (mean age 49 ± 16years, 73% female) from 6 Faith based Centres. More males than females reported smoking tobacco (14.5% vs. 0.7%) and been physically active (64.5% vs. 52.7%) while more females were obese (29.6 kg/m2 vs. 14.5 kg/m2) and had a higher mean waist circumference (89.0 cm IQR 75-116 cm vs. 84.2 cm IQR 72–107 cm), hip circumference (101.5 ± 10.6 cm vs. 96.4 ± 8.6 cm) and waist-to-hip ratio (0.86 ± 0.1 cm vs. 0.87 ± 0.1 cm) than males. The prevalence of confirmed hypertension and T2DM was 27.9% and 3.5% respectively with no observed sex differences. We observed deficits in the hypertension and T2DM care cascade with reported low awareness, treatment and uncontrolled levels. A 3-month follow up showed a retention in care of 100% in month one and 94.9% in the third month. There was an increase in treatment (39.4% in month-1 and 82.8% in month-3) and control (26.3% in month-1 and 76.3% in month-3) of hypertension and T2DM combined. Conclusion: Faith-based centres have the potential to enhance the screening, linkage to the healthcare system, and management of hypertension and T2DM. This improvement over the routine system could lead to earlier diagnoses, a reduction in complications, and decreased premature mortality from cardiovascular diseases. Consequently, these efforts would contribute significantly to achieving SDG 3. [ABSTRACT FROM AUTHOR]

Background: Islet transplantation is a recommended treatment for type 1 diabetes but is limited by donor organ shortage. This study introduces an innovative approach for improving the differentiation and functionality of insulin-producing cells (IPCs) from iPSCs using 3D spheroid formation and hydrogel matrix as an alternative pancreatic islet source. The extracellular matrix (ECM) is crucial for pancreatic islet functionality, but finding the ideal matrix for β-cell differentiation has been challenging. We aimed to advance IPC differentiation and maturation through an esterified collagen hydrogel, comparing its effectiveness with conventional basement membrane extract (BME) hydrogels. Methods: iPSCs were differentiated into IPCs using a small molecule-based sequential protocol, followed by spheroid formation in concave microwells. Rheological analysis, scanning electron microscopy, and proteomic profiling were used to characterize the chemical and physical properties of each matrix. IPCs, both in single-cell form and as spheroids, were embedded in either ionized collagen or BME hydrogels, which was followed by assessments of morphological changes, pancreatic islet-related gene expression, insulin secretion, and pathway activation using comprehensive analytical techniques. Results: Esterified collagen hydrogels markedly improved the structural integrity, insulin expression, and cell-cell interactions in IPC spheroids, forming densely packed insulin-expressing clusters, in contrast to the dispersed cells observed in BME cultures. Collagen hydrogel significantly enhanced the mRNA expression of crucial endocrine markers and maturation factors, with IPC spheroids showing accelerated differentiation from day 5, suggesting a faster differentiation compared to single cells in hydrogel encapsulation. Insulin secretion in response to glucose in collagen environments, with a GSIS index of 2.46 ± 0.05, exceeded those in 2D and BME, demonstrating superior pancreatic islet functionality. Pathway analysis highlighted enhanced insulin secretion capabilities, evidenced by the upregulation of genes like Secretogranin III and Chromogranin A in collagen cultures. In vivo transplantation results showed that collagen hydrogel enhanced cluster integrity, tissue integration, and insulin secretion compared to non-embedded IPCs and BME groups. Conclusion: Esterified collagen hydrogels demonstrated superior efficacy over 2D and BME in promoting IPC differentiation and maturation, possibly through upregulation of the expression of key secretion pathway genes. Our findings suggest that using collagen hydrogels presents a promising approach to enhance insulin secretion efficiency in differentiating pancreatic β-cells, advancing cell therapy in diabetes cell therapy. [ABSTRACT FROM AUTHOR]

Background: The role of plant-based dietary patterns in preventing cardiovascular disease (CVD) among individuals with prediabetes and diabetes remains unclear. We aimed to evaluate the associations of plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI) with cardiovascular disease (CVD) risk and explore potential contributing factors among people with prediabetes and diabetes. Methods: A total of 17,926 participants with prediabetes and 7798 with diabetes were enrolled from the UK Biobank between 2006 and 2010 and followed until the end of 2020. We calculated the PDI, hPDI, and uPDI based on 18 major food groups including plant-based foods and animal-based foods and applied Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD risk related to PDI, hPDI, and uPDI. Decomposition analysis was performed to assess the role of dietary components, and mediation analysis was performed to assess the potential mediating role of serum biomarkers underlying these associations. Results: A total of 2324 CVD events were documented among individuals with prediabetes, while 1461 events occurred among patients with diabetes. An inverse association was found between hPDI and CVD risk among individuals with prediabetes (HR T3 vs. T1 = 0.88, 95% CI = 0.79–0.98, Ptrend = 0.025) but not those with diabetes. A positive association was found between uPDI and CVD risk among individuals with prediabetes (HR T3 vs. T1 = 1.17, 95% CI = 1.05–1.30, Ptrend = 0.005) and those with diabetes (HR T3 vs. T1 = 1.14, 95% CI = 1.00–1.29, Ptrend = 0.043). High-sugar-sweetened beverages (SSB) intake accounted for 35% of the hPDI-CVD association and 15% of the uPDI-CVD association among individuals with prediabetes, whereas low intake of whole grain accounted for 36% of the association among patients with diabetes. Elevated cystatin C levels explained the largest proportion of the association between uPDI and CVD risk among individuals with prediabetes (15%, 95% CI = 7–30%) and diabetes (44%, 95% CI = 9–86%). Conclusions: Adherence to an unhealthy plant-based diet is associated with a higher CVD risk in people with prediabetes or diabetes, which may be partially attributed to low consumption of whole grains, high intake of SSB, and high blood cystatin C levels. [ABSTRACT FROM AUTHOR]

Background: Telemedicine holds immense potential to revolutionise healthcare delivery, particularly in resource-limited settings and for patients with chronic diseases. Despite proven benefits and policy reforms, the use of telemedicine remains low due to several patient, technology, and system-level barriers. Assisted telemedicine employs trained health professionals to connect patients with physicians, which can improve access and scope of telemedicine. The study aims to describe the design, service utilisation and chronic disease outcomes following the implementation of an assisted telemedicine initiative. Methods: This is an observational implementation study. Barriers and potential solutions to the implementation of telemedicine were identified through interviews with key stakeholders. The assisted telemedicine solution using an interoperable platform integrating electronic health records, point-of-care diagnostics, and electronic clinical decision support systems was designed and piloted at three telemedicine clinics in Tamil Nadu, India. Nurses were trained in platform use and facilitation of tele-consultations. Health records of all patients from March 2021 to June 2023 were included in the analysis. Data were analysed to assess the utilisation of clinic services and improvements in health outcomes in patients with diabetes mellitus and hypertension. Results: Over 2.4 years, 11,388 patients with a mean age of 45 (± 20) years and median age of 48 years, predominantly female (59.3%), accessed the clinics. The team completed 15,437 lab investigations and 26,998 consultations. Among 5542 (48.6%) patients that reported chronic conditions, diabetes mellitus (61%) and hypertension (45%) were the most frequent. In patients with diabetes mellitus and hypertension, 43% and 75.3% were newly diagnosed, respectively. Diabetes mellitus and hypertension patients had significant reductions in fasting blood sugar (-33.0 mg/dL (95% CI (-42.4, -23.7, P < 0.001)), and systolic (-9.6 mmHg (95% CI (-12.1, -7.0), P < 0.0001)) and diastolic blood pressure (-5.5 mmHg (95% CI (-7.0, -4.08), P < 0.0001)) at nine months from first visit, respectively. Conclusions: The 'Digisahayam' model demonstrated feasibility in enhancing healthcare accessibility and quality by bridging healthcare gaps, diagnosing chronic conditions, and improving patient outcomes. The model presents a scalable and sustainable approach to revolutionising patient care and achieving digital health equity, with the potential for adaptation in similar settings worldwide. [ABSTRACT FROM AUTHOR]

Background: Animation has promise for teaching complex health content through smartphone applications. However, smartphones have had limited use in Thailand for health literacy improvement among adults with chronic diseases. This study aims to explore the perceptions of adults with diabetes and/or hypertension resulting from 2D short animated videos for literacy against chronic disease that are available via smartphones. Methods: Four animated videos were initially developed based on clinical practice guidelines and nursing experience. Physicians, an expert in health education, and an animation team developed and revised scripts and storyboards of the animated videos. Lastly, videos were validated by physicians and health educators for content breadth and depth and by media experts for motion graphics and illustration. Each video presents a different situation in diabetes, hypertension, missing appointments, and obesity, ranging from 2.18 to 4.14 min in duration. The inclusion criteria were adults 35–70 years old with diabetes or hypertension who received care from primary care units. Thematic analysis was performed on the extracted data. Results: Twenty participants with a mean age of 58.4 years (SD 6.7; ranged 41–68) were focus-group interviewed. Three animation elements were assessed, including presentation, impacts, and suggestions. Participants had positive responses regarding the presentation (suitability of images and smooth motion graphics, short length of videos, simple language, understandable content, and clear sound) and impacts (recalling information, enhancing engagement, and motivating health awareness and behavior change). Suggested improvements were for a bigger font size for subtitles and considering the use of spoken text instead of on-screen text for recommendations at the end of the animations. Conclusions: Animated videos are acceptable for delivering health information. Pilot testing animated videos for promoting literacy against chronic diseases in adults with diabetes and hypertension is needed for optimal utility. [ABSTRACT FROM AUTHOR]

Background: This study aims to explore the relationship between magnesium depletion score (MDS) and periodontitis in US adults using data from the National Health and Nutritional Examination Survey (NHANES) 2009–2014. Methods: This cross-sectional study's outcome was periodontitis, defined by the CDC/AAP using clinical periodontal parameters. The exposure of this study was MDS, which was calculated according to four parameters (diuretic use, proton pump inhibitor use, renal function and alcohol consumption). Weighted univariable and multivariable logistic regression analyses were performed to explore the association between MDS intake and periodontitis. Confounding factors included in the adjusted model were age, sex, race, income, smoking status, dietary magnesium, obesity, diabetes, hypertension, education level, recreational activity, and work activity. Results: A total of 8,628 participants over the age 30 were included in our study. Individuals with high level of magnesium deficiency were more likely referred to poorer periodontal health in both crude model (OR = 2.01, 95% CI: 1.54–2.61, p < 0.0001) and fully adjusted model (OR = 1.35, 95% CI: 1.03–1.77, p = 0.03). Conclusions: MDS is positively associated with moderate/severe periodontitis. Further longitudinal studies are needed to understand the impact of MDS on periodontitis. [ABSTRACT FROM AUTHOR]

Background: Early laparoscopic cholecystectomy (ELC) in the setting of acute calculous cholecystitis (ACC) requires to be performed by highly-skilled surgeons to avoid complications. The purpose of this study is to identify preoperative factors that would predict difficult ELC among patients with ACC prior to proceeding with surgery. Methods: We retrospectively reviewed all patients who received ELC within 10 days from the onset of symptoms of ACC between August 1, 2018, and December 31, 2022. They were divided into 2 groups according to the difficulty of surgery. Results: 149 patients with ACC received ELC during the study period. ELC was considered difficult in 52 patients (35%). Five preoperative factors were identified as significant predictors of difficult ELC (DELC) on multivariate analysis: duration of acute attack ≥ 4 days from the onset of symptoms till surgery (OR 34.4, P < 0.001), ultrasound showing largest gallstone size > 20 mm (OR 20.2, P = 0.029), ultrasound showing gallstone impaction in Hartmann's pouch (OR 7.2, P = 0.017), history of prior episode(s) of acute attack (OR 6.8, P = 0.048), and diabetes mellitus (OR 5.8, P = 0.046). Conclusion: Careful preoperative assessment of patients with ACC is crucial among junior surgeons with limited surgical expertise prior to proceeding with ELC to identify those at risk of DELC to potentially reduce postoperative morbidity and mortality. If encountered, a management plan should be made, and surgery should proceed only upon confirming the availability of experienced surgeons in the field of biliary and laparoscopic surgery to supervise or assist in the procedure. Alternatively, such group of patients should rather be transferred to more advanced surgical centers which offer higher level of care to maintain patient safety and optimal surgical outcomes. More importantly, bail-out procedures should always be resorted to whenever DELC is encountered intraoperatively to prevent further surgical damage. [ABSTRACT FROM AUTHOR]