Journal of Diabetes Research最新文献

Background: This study investigates the impact of a high-sugar environment on H9C2 cardiomyocytes and explores the protective effects of carvedilol in the context of diabetic cardiomyopathy (Dia-CM). Transcriptomic analysis identified 21,655 differentially expressed genes associated with Dia-CM, demonstrating significant separation among samples. Methods: H9C2 cardiomyocytes were cultured in a high-sugar environment to simulate Dia-CM conditions. Cell viability, cytokine levels, and protein expression were assessed using CCK-8 assays, ELISA, and Western blot techniques. Intervention experiments with NLRP3, caspase-1, and ROS inhibitors were conducted to evaluate their protective effects. The therapeutic potential of carvedilol was assessed by examining its impact on cell viability, cytokine levels, and key biomarkers. An in-depth analysis of carvedilol's regulatory effects on ROS and key proteins in H9C2 cells was also conducted. Results: In vitro, a high-sugar environment significantly reduced H9C2 cell survival, increased ROS levels, activated inflammatory responses, and upregulated NLRP3, caspase-1, and GSDMD-N proteins. Inhibitors of NLRP3, caspase-1, and ROS ameliorated these effects. Carvedilol treatment improved cell activity, reduced inflammatory cytokine levels, suppressed ROS production, and downregulated NLRP3, pro-caspase-1, GSDMD-N, and p-NF-κB proteins. Moderate-dose carvedilol exhibited optimal intervention effects. Conclusions: A high-sugar environment induces cardiomyocyte damage through ROS production and NLRP3 inflammasome activation. Inhibitors of NLRP3, caspase-1, and ROS provide effective protection. Carvedilol significantly mitigates the detrimental effects of a high-sugar environment on H9C2 cardiomyocytes, potentially through inhibiting the NLRP3-ASC inflammasome and caspase-1/GSDMD-dependent signaling pathway-mediated pyroptosis. These findings offer insights into Dia-CM mechanisms and highlight carvedilol as a promising therapeutic intervention.

Diabetic retinopathy (DR) is one of the most common complications of diabetes and induces severe visual impairment worldwide. Endothelial cell dysfunction plays an important role in the pathogenesis of DR. Here, we keep a watchful eye on α/β-hydrolase domain-containing 1 (ABHD1), a potential regulator in lipid metabolism and neovascularization. Results revealed that ABHD1 expression increased both in retina tissues of DR patients and in high-glucose-treated human retina endothelial cells. Inhibition of ABHD1 remitted endothelial cell proliferation and migration. And GSEA uncovered that ABHD1 knockdown remits endothelial cell chemotaxis and intermediate filament (IF) might be mediated in the progress by regulating keratin 1 (KRT1) and keratin 2 (KRT2). Therefore, we assume that ABHD1 is concerned with endothelial cell proliferation and migration in DR, consequently leading to pathological neovascularization. The findings may provide a potential therapeutic target for DR.

Background: Diabetes distress is a common emotional issue for those living with diabetes, which has the potential to negatively impact well-being, management behaviors, and HbA1c levels. These implications have led to diabetes distress becoming an important consideration in diabetes healthcare and management. Nonetheless, discussions remain ongoing on how to best conceptualize this experience. Recent research has attempted to enhance conceptualization by considering the underlying emotional mechanisms that may underpin the highly contextualized experience of diabetes distress. Qualitative insights can further add to these understandings; however, the research in this remit is yet to be systematically reviewed. This review therefore sought to add to the growing body of literature attempting to better conceptualize diabetes distress and the underlying mechanisms that may contribute to this experience. A secondary aim was to leverage this understanding to consider ways to improve patient-healthcare interactions. Methods: A qualitative systematic review and thematic synthesis was undertaken. Eligible studies were identified through PsycINFO, MEDLINE, CINAHL, and EMBASE databases from November 2020 to May 2021. Study quality was assessed using the McMaster Critical Review Form. Results: Nineteen papers were included in the review. The analysis resulted in seven descriptive themes which contributed to three analytical themes: (1) threatened autonomy, (2) sense of helplessness, and (3) negative sense of self. These results highlight that a major area underpinning experiences of diabetes distress is not feeling in control. Conclusions: Consideration should be given to how psychological factors, such as locus of control and learned helplessness, may constitute underlying mechanisms impacting emotional regulation in those experiencing diabetes distress. Clinicians should consider including and leading discussions around distress during appointments, as well as using approaches that promote patient autonomy and empowerment.

Background: The oral safety of Lithocarpus litseifolius (Hance) Chun (sweet tea) that has antihyperglycemic potential has been verified. However, its specific application and action mechanism in the treatment of gestational diabetes mellitus (GDM) are still unclear. Methods: Total water-soluble flavonoids extracted from L. litseifolius (Hance) Chun (sweet tea) were applied to GDM mice. The glucose tolerance, insulin sensitivity, and histopathology of the GDM mice were evaluated through an intraperitoneal glucose tolerance test (IPGTT), an intraperitoneal insulin tolerance test (IPITT), and histochemistry. The possible mechanism was analysed through network pharmacology. Results: Compared with those in GDM model mice (MD group), blood glucose levels indicating both glucose tolerance and insulin sensitivity were improved in GDM mice treated with total water-soluble flavonoids (LLHC group) but were greater than those in normal control mice (NC group). The number of apoptotic liver cells was significantly lower in the LLHC group than in the MD group, but greater than that in the NC group. Multiple targets and signalling pathways that were acted by eight main active ingredients were involved in the process by which total water-soluble flavonoids protect against GDM. The main mechanism involved quercetin (10 targets) and luteolin (8 targets), which acted on the effector target of GAA through six main signalling pathways around the AKT1 core axis. Conclusion: Oral administration of total water-soluble flavonoids can alleviate glucose intolerance and insulin resistance via the inhibition of liver cell apoptosis. The main active ingredients act on GAA through the signalling pathways of the AKT1 core axis.

Background: Hypertension (HTN) is common in patients with type 2 diabetes mellitus (T2DM). Patients with both T2DM and HTN have a higher risk of heart disease, kidney disorders, and mortality than those with either HTN or T2DM alone. Patients' psychological well-being plays a significant role in the optimum management of these chronic conditions. This study is aimed at determining the current prevalence of HTN and its related clinical and psychological factors in patients with T2DM. Methods: This cross-sectional study was conducted at the Korle-Bu Teaching Hospital with 156 patients diagnosed with T2DM. A structured questionnaire was used to obtain information on sociodemographic and clinical characteristics. In addition, the following information was obtained from the patients' clinical files: blood pressure, height, weight, waist circumference, serum creatinine, and urine protein. Depression, resilience, and coping skills of the participants were measured using the Brief Symptom Inventory-18, Resilience Scale for Adults, and Brief COPE Inventory, respectively. Data were analyzed using STATA version 18, with a significance level of p < 0.05. Results: The median age of respondents was 62.0 (IQR: 51.50, 67.00) years. The majority was female (76.3%). The prevalence of HTN among the patients with T2DM was 79.9% (95% CI: 72.7-85.9). The average body mass index (BMI) of the patients was 28871kg/m² with 34.8% and 36.2% being overweight and obese, respectively. The average HBA1C level was 8.6 ± 2.1 with 71.8% of the patients having poor glycemic control. Increasing age, caregiver, and personal resilience were factors significantly associated with HTN (p value of <0.05) among patients with T2DM. Conclusion: The prevalence of HTN among T2DM patients was high; age, caregiver, and personal resilience significantly predicted HTN among T2DM patients. These findings have implications for healthcare providers in implementing strategies to reduce central obesity and incorporating resilience as an important factor in improving treatment outcomes in patients with T2DM.

Background: Diabetic peripheral neuropathy (DPN) impacts approximately 50% of individuals with Type 2 diabetes mellitus (T2DM), leading to severe complications such as foot ulcers and amputations. Notably, visceral adiposity is increasingly recognized as a pivotal factor in augmenting the risk of DPN. We aim to evaluate the correlation between obesity-related body composition, particularly visceral fat, and DPN to facilitate early identification of high-risk patients with T2DM. Methods: This cross-sectional analysis encompassed 113 T2DM patients from the Department of Endocrinology and Metabolism at the Second Affiliated Hospital of Fujian Medical University, conducted between September 2020 and January 2021. Patients were categorized into two cohorts: those with DPN (DPN group) and those without (NDPN group). We utilized bioelectrical impedance analysis (BIA) to determine body measurements, such as weight and visceral fat area, in addition to collecting clinical and biochemical data. Logistic regression was employed to analyze the data. Results: The study uncovered a statistically significant difference in the visceral fat area between the DPN and NDPN groups (p = 0.048). Through multivariate logistic regression analysis, the visceral fat area was identified as an independent risk factor for DPN among T2DM patients (OR 1.027; 95% CI 1.004-1.051, p = 0.022). Other significant risk factors included the duration of diabetes and the presence of diabetic retinopathy. Conclusion: The visceral fat area serves as an independent risk factor for DPN in individuals with T2DM. Implementing measures to assess and manage visceral obesity could be vital in the prevention and management of DPN. This underscores the value of technologies such as BIA in clinical and community settings for early intervention.

Background: The study investigates the association between lipid accumulation product (LAP) and the risk of prediabetes and diabetes. LAP, a measure indicating lipid overaccumulation, is hypothesized to be a significant predictor for these conditions. This research utilizes data from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2018. Methods: The study followed a structured methodology, starting with data extraction from the NHANES database. Participants' eligibility was determined based on specific inclusion and exclusion criteria, resulting in a final sample size of 24,121 individuals. LAP was calculated using established formulas for men and women. The diagnosis of prediabetes and diabetes was based on standard medical criteria, including HbA1c levels, fasting plasma glucose, and oral glucose tolerance test (OGTT) results. Covariates like demographic variables, lifestyle factors, and other health indicators were also considered. Statistical analysis involved categorizing LAP into quartiles and employing logistic regression models to examine the relationship between LAP and the risk of prediabetes and diabetes. Results: Participants in the highest LAP quartile exhibited distinct characteristics: older age, lower education levels, more former smokers and drinkers, higher blood pressure and cholesterol levels, and greater use of medications. A positive association was observed between LAP and the incidence of prediabetes and diabetes across all models. Specifically, each 10-unit increase in LAP was linked to a 22% increase in risk. Nonlinear relationships were also explored, revealing an inflection point in the risk correlation at an LAP value of 68.1. Conclusion: The study concludes that LAP is a significant predictor of prediabetes and diabetes risk, with higher LAP levels correlating with increased risk. This finding underscores the potential of LAP as a useful marker in identifying individuals at higher risk for these conditions. It also highlights the importance of considering LAP in preventive health strategies.

Globally, adherence to Type 2 diabetes mellitus (T2DM) medications remains suboptimal. There are limited insights, however, on this issue in the northern region of Ethiopia. This cross-sectional study at Alamata General Hospital investigated the interplay between patients' medication beliefs, diabetes knowledge, adherence, and glycemic control. Data collection was done using structured questionnaires and chart reviews, while descriptive and inferential statistics were for the analysis. Among 305 T2DM patients, poor medication adherence was prevalent (44.6%), alongside suboptimal glycemic control (75.7%). Patients diagnosed for over a decade had an adjusted odds ratio (AOR) of 3.87 for nonadherence, while high concern about medication side effects was associated with a 20.63-fold higher nonadherence risk (AOR = 20.63). Low disease awareness increased nonadherence risk by 4.54 times (AOR = 4.54), while a strong belief in medication necessity was protective (AOR = 0.21). Poor glycemic control was associated with educational background, diabetes awareness, monthly income, and treatment modality. Urgently needed are tailored diabetes education programs in Northern Ethiopia to counteract high rates of poor medication adherence (AOR = 3.87) and glycemic control among T2DM patients. Targeted interventions, emphasizing knowledge enhancement and reinforcing positive beliefs, are essential for improving outcomes in this population.

Modern lifestyle changes, especially the consumption of a diet high in salt, sugar, and fat, have contributed to the increasing incidence and prevalence of chronic metabolic diseases such as diabetes, obesity, and gout. Changing lifestyles continuously shape the gut microbiota which is closely related to the occurrence and development of metabolic diseases due to its specificity of composition and structural diversity. A large number of pathogenic bacteria such as Yersinia, Salmonella, Shigella, and pathogenic E. coli in the gut utilize the type III secretion system (T3SS) to help them resist host defenses and cause disease. Although the T3SS is critical for the virulence of many important human pathogens, its relationship with metabolic diseases remains unknown. This article reviews the structure and function of the T3SS, the disruption of intestinal barrier integrity by the T3SS, the changes in intestinal flora containing the T3SS in metabolic diseases, the possible mechanisms of the T3SS affecting metabolic diseases, and the application of the T3SS in the treatment of metabolic diseases. The aim is to provide insights into metabolic diseases targeting the T3SS, thereby serving as a valuable reference for future research on disease diagnosis, prevention, and treatment.

Objective: This study elucidated the mechanistic role of Cyathulae Radix (CR) in type 2 diabetes mellitus (T2DM) through bioinformatics analysis and experimental validation. Methods: Components and targets of CR were retrieved from the traditional Chinese medical systems pharmacology, while potential T2DM targets were obtained from GeneCards and Online Mendelian Inheritance in Man databases. Intersecting these datasets yielded target genes between CR and T2DM. Differential genes were used for constructing a protein-protein interaction network, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking and dynamics simulations were performed using AutoDock and GROMACS, respectively, and in vitro experiments validated the results. Experiments evaluated the effect of CR on T2DM pancreatic β-cells. Results: Bioinformatics analysis identified four active compounds of CR, 157 related genes, and 5431 T2DM target genes, with 141 shared targets. Key targets such as JUN, MAPK1, and MAPK14 were identified through topological analysis of the PPI network. GO analysis presented 2663 entries, while KEGG analysis identified 161 pathways. The molecular docking results demonstrated favorable binding energy between the core components and the core proteins. Among them, JUN-rubrosterone, MAPK1-rubrosterone, and MAPK14-rubrosterone deserved further investigation. Molecular dynamics results indicated that all of them can form stable binding interactions. CR could inhibit the expression of JUN, MAPK1, and MAPK14, promote insulin secretion, alleviate apoptosis, and regulate autophagy in INS-1 cells. Conclusion: This study suggests CR approach to T2DM management by multitarget and multipathway provides a scientific basis for further research on the hypoglycemic effect of CR.