According to the gut-kidney axis theory, gut microbiota (GM) has bidirectional crosstalk with the development of diabetic kidney disease (DKD). However, empirical results have been inconsistent, and the causal associations remain unclear. This study was aimed at exploring the causal relationship between GM and DKD as well as the glomerular filtration rate (GFR) and urinary albumin-to-creatinine ratio (UACR). Two-sample Mendelian randomisation (MR) analysis was performed with inverse-variance weighting as the primary method, together with four additional modes (MR-Egger regression, simple mode, weighted mode, and weighted median). We utilised summary-level genome-wide association study statistics from public databases for this MR analysis. Genetic associations with DKD were downloaded from the IEU Open GWAS project or CKDGen consortium, and associations with GM (196 taxa from five levels) were downloaded from the MiBioGen repository. In forward MR analysis, we identified 13 taxa associated with DKD, most of which were duplicated in Type 2 diabetes with renal complications but not in Type 1 diabetes. We observed a causal association between genetic signature contributing to the relative abundance of Erysipelotrichaceae UCG003 and that for both DKD and GFR. Similarly, host genetic signature defining the abundance of Ruminococcaceae UCG014 was found to be simultaneously associated with DKD and UACR. In reverse MR analysis, the abundance of 14 other GM taxa was affected by DKD, including the phylum Proteobacteria, which remained significant after false discovery rate correction. Sensitivity analyses revealed no evidence of outliers, heterogeneity, or horizontal pleiotropy. Our findings provide compelling causal genetic evidence for the bidirectional crosstalk between specific GM taxa and DKD development, contributing valuable insights for a comprehensive understanding of the pathological mechanisms of DKD and highlighting the possibility of prevention and management of DKD by targeting GM.

Vitamin E, an essential micronutrient with antioxidant potential, can dramatically reduce the cardiovascular risk in individuals with haptoglobin (Hp) 2-2 genotype diabetes; however, the underlying mechanism remains unclear. The objective of this study is to evaluate the effect of vitamin E supplementation on high-density lipoprotein (HDL) levels and function in individuals with diabetes stratified by Hp genotype. All relevant studies published up to May 2023 were systematically reviewed using PubMed, Cochrane Library, Web of Science, Chinese Wanfang, China Science and Technology Journal, and Chinese National Knowledge Infrastructure databases. Randomized controlled trials that evaluated the effects of vitamin E supplementation on HDL levels were included. The outcomes assessed were changes in HDL concentrations, cholesterol efflux, and HDL-associated lipid peroxides. In total, 163 publications were selected. Based on inclusion and exclusion selection and quality assessment, five studies with 463 participants were included. Vitamin E supplementation did not exert any effect on HDL levels in individuals with diabetes with any Hp genotype. Three of the five studies revealed that vitamin E improved cholesterol efflux and HDL lipid peroxides in individuals with Hp2-2 diabetes but did not positively impact HDL function in Hp1 carriers. Although vitamin E supplementation did not significantly impact HDL levels in individuals with diabetes of any Hp genotype, it may improve HDL function in individuals with Hp2-2 diabetes. These findings indicate a pharmacogenetic interaction between vitamin E and the Hp genotype on HDL function. Moreover, vitamin E supplementation may be an effective strategy for specific individuals with diabetes.

The relationship between dietary flavonoid intake and mortality in the diabetic kidney disease (DKD) population is unknown. So this study is aimed at investigating the association of total dietary flavonoid intake and their subclasses with all-cause and cardiovascular disease (CVD) mortality. Data of this cohort study were extracted from the NHANES (2007-2010 and 2017-2018). The survival status of participants was determined by linking to the National Death Index through the end of 2019. Flavonoid intake was measured using two 24-h dietary recall interviews. The Kaplan-Meier curves and weighted Cox proportional hazard regression models were used to assess the effect of dietary flavonoid intake on CVD and all-cause mortality, with adjustments for multiple covariates. A total of 1155 participants were included for analysis. After a median follow-up of 76.36 (S.E: 3.24) months, 409 participants died of all-cause mortality, of which 138 died of CVD. In the fully adjusted model, higher total dietary flavonoids intake (HR = 0.69, 95% CI: 0.52-0.92) was associated with lower all-cause mortality and subclasses of higher flavones (HR = 0.60, 95% CI: 0.35-0.85) was also with lower all-cause mortality. In subclasses of flavonoids, higher intake of both anthocyanidins (HR = 0.54, 95% CI: 0.28 to 0.87) and flavones (HR = 0.50, 95% CI: 0.28-0.87) were associated with lower odds of CVD mortality. Higher flavonoid intake was associated with a reduced risk of CVD and all-cause mortality in DKD. Higher flavonoid intake provides a potential opportunity to improve the prognosis of DKD. And future research into the mechanisms between flavonoids and mortality is needed.

Our goal was to examine the causal link between blood metabolites, their ratios, and the risk of developing proliferative diabetic retinopathy (PDR) from a genetic insight. Summary-level data about 1400 blood metabolites and their ratios, as well as PDR, were sourced from prior genome-wide association studies (GWAS). A two-sample univariate and multivariate Mendelian randomization (MR) approach was utilized. Additionally, metabolic pathway analysis and sensitivity analysis were also conducted. After adjusting for multiple tests, four blood metabolites significantly correlated with PDR risk. Two ceramides, including glycosyl-N-palmitoyl-sphingosine (d18:1/16:0) (odds ratio [OR] = 1.12, 95% confidence interval (CI): 1.06-1.17, < 0.001, false discovery rate (FDR) = 0.005) and glycosyl-N-behenoyl-sphingadienine (d18:2/22:0) (OR = 1.11, 95% CI: 1.06-1.16, < 0.001, FDR = 0.017), were linked to increased risk. Additionally, 3-methylcytidine (OR = 1.05, 95% CI: 1.03-1.08, < 0.001, FDR = 0.021) also posed a risk, whereas (N(1)+N(8))-acetylspermidine (OR = 0.91, 95% CI: 0.87-0.94, < 0.001, FDR = 0.002) appeared protective. Multivariable MR analysis further confirmed a direct, protective effect of (N(1)+N(8))-acetylspermidine on PDR risk (OR = 0.94, 95% CI: 0.89-1.00, = 0.040). The sensitivity analysis results indicated that evidence for heterogeneity and pleiotropy was absent. These metabolites have the potential to be used as biomarkers and are promising for future research into the mechanisms and drug targets for PDR.

This study is aimed at comparing whole exome sequencing (WES) data with the clinical presentation in children with type 1 diabetes onset ≤ 5 years of age (EOT1D). WES was performed in 99 unrelated children with EOT1D with subsequent analysis to identify potentially deleterious rare variants in MODY genes. High-resolution HLA class II haplotyping, SNP genotyping, and T1D-genetic risk score (T1D-GRS) were also evaluated. Eight of the ninety-nine EOT1D participants carried a potentially deleterious rare variant in a MODY gene. Rare variants affected five genes: ( = 1), ( = 2), ( = 1), ( = 2), and ( = 2). At diagnosis, these children had a mean age of 3.0 years, a mean HbA1c of 10.5%, a detectable C-peptide in 5/8, and a positive islet autoantibody in 6/7. Children with MODY variants tend to exhibit a lower number of pancreatic autoantibodies and a lower fasting C-peptide compared to EOT1D without MODY rare variants. They also carried at least one high-risk DR3-DQ2 or DR4-DQ8 haplotype and exhibited a T1D-GRS similar to the other individuals in the EOT1D cohort, but higher than healthy controls. WES found potentially deleterious rare variants in MODY genes in 8.1% of EOT1D, occurring in the context of a T1D genetic background. Such genetic variants may contribute to disease precipitation by a -cell dysfunction mechanism. This supports the concept of different endotypes of T1D, and WES at T1D onset may be a prerequisite for the implementation of precision therapies in children with autoimmune diabetes.

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. 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. 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-B proteins. Moderate-dose carvedilol exhibited optimal intervention effects. 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.

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. 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. 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. 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.

The prevalence of T2DM has been increasing dramatically over recent decades, about 537 million people in 2021. LADA type diabetes, a subtype of diabetes that exhibits characteristics of both T2DM and autoimmune beta-cell destruction similar to T1DM, but with a later onset. The aim of this study is to analyze the main research field on LADA type, including analysis of countries, institutions, journals, authors, and keywords. This research utilized a descriptive bibliometric design. We collected and analyzed data from 672 publications indexed in the Web of Science and Scopus databases, covering the period from 1994 to January 2024. The bibliometric analysis included English-language research articles that involved studies on patients with LADA type diabetes, aged 18 years or older. RStudio and the Bibliometrix R package were used for data merging and for performing statistical and visual analyses. The annual publication shows an upward trend over the period, with the highest number of publications per year in 2021. The study showed that China leads in the number of articles, with 101 papers published. The United Kingdom demonstrates significant international collaborations, particularly with Germany. The top institutions in terms of the number of published articles are the Norwegian University of Science and Technology in the Kingdom of Norway, followed by the Central South University in China. Tuomi has shown significant long-term publication impact, while Zhou ranks among the most frequently cited authors. is one of the most important scientific journals in diabetology with the highest impact factor of 16.2. This abstract summarizes a comprehensive bibliometric analysis that provides insights into the global research field of LADA type, underscoring the importance of international collaboration and the significant contributions of leading countries and institutions in shaping our understanding of this complex subtype of diabetes.

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. 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 < 0.05. 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/m 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 ( value of <0.05) among patients with T2DM. 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.

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. 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. The study uncovered a statistically significant difference in the visceral fat area between the DPN and NDPN groups ( = 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, = 0.022). Other significant risk factors included the duration of diabetes and the presence of diabetic retinopathy. 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.

The oral safety of (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. Total water-soluble flavonoids extracted from (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. 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. 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.

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. 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. 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. 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.

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 /-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.

Obesity is a predisposing risk factor for type 2 diabetes mellitus (T2DM). Actually, not only obese/overweight but also nonobese/lean individuals may be prone to T2DM. This study is aimed at identifying the contribution of adipose tissue to the development of nonobese diabetes (NOD) and obese diabetes (OD). Serum samples from the nonobese nondiabetes (NOND, = 47, age = 46.8 ± 8.4, BMI ≤ 23.9 kg/m) controls, NOD ( = 48, age = 50.7 ± 6.5, BMI ≤ 23.9 kg/m) and OD (n = 65, = 49.8 ± 10.2, BMI ≥ 28 kg/m) patients were utilized to measure the expression of metabolic indicators, adipocytokines, inflammatory factors. Different adipose depots from offspring with corresponding blood glucose and obesity levels of a spontaneously diabetic gerbil line with various degrees of diabetic penetrance and body weights were examined for adipocytokines and inflammation factors detected by ELISA and western blot. Adipose tissue volume and fat cell size of the gerbils were evaluated by magnetic resonance imaging and immunohistochemistry, respectively. The study yielded four key findings. Firstly, in comparison to the NOD group, the OD group exhibited more severe insulin resistance (IR) and metabolic dysfunction in both patients and gerbils, attributed to higher visceral adipose tissue mass and larger fat cell sizes. Secondly, in gerbils, gonadal fat deposition was linked to obesity development, whereas kidney fat deposition correlated with obesity and diabetes occurrence. Thirdly, in both patients and gerbils, the interplay between adiponectin and leptin levels in serum may significantly influence the development of obesity and diabetes. Lastly, heightened expression of MCP3 in gerbils' kidney adipose tissue may serve as a pivotal factor in initiating obesity-associated diabetes. Our study, which may be considered a pilot investigation, suggests that the interaction of adipocytokines and inflammation factors in different adipose depots could play diverse roles in the development of diabetes or obesity.

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.

Propionate metabolism is important in the development of diabetes, and fibrosis plays an important role in diabetic nephropathy (DN). However, there are no studies on biomarkers related to fibrosis and propionate metabolism in DN. Hence, the current research is aimed at evaluating biomarkers associated with fibrosis and propionate metabolism and to explore their effect on DN progression. The GSE96804 (DN : control = 41 : 20) and GSE104948 (DN : control = 7 : 18) DN-related datasets and 924 propionate metabolism-related genes (PMRGs) and 656 fibrosis-related genes (FRGs) were acquired from the public database. First, DN differentially expressed genes (DN-DEGs) between the DN and control samples were sifted out via differential expression analysis. The PMRG scores of the DN samples were calculated based on PMRGs. The samples were divided into the high and low PMRG score groups according to the median scores. The PM-DEGs between the two groups were screened out. Second, the intersection of DN-DEGs, PM-DEGs, and FRGs was taken to yield intersected genes. Random forest (RF) and recursive feature elimination (RFE) analyses of the intersected genes were performed to sift out biomarkers. Then, single gene set enrichment analysis was conducted. Finally, immunoinfiltrative analysis was performed, and the transcription factor (TF)-microRNA (miRNA)-mRNA regulatory network and the drug-gene interaction network were constructed. There were 2633 DN-DEGs between the DN and control samples and 515 PM-DEGs between the high and low PMRG score groups. In total, 10 intersected genes were gained after taking the intersection of DN-DEGs, PM-DEGs, and FRGs. Seven biomarkers, namely, SLC37A4, ACOX2, GPD1, angiotensin-converting enzyme 2 (ACE2), SLC9A3, AGT, and PLG, were acquired via RF and RFE analyses, and they were found to be involved in various mechanisms such as glomerulus development, fatty acid metabolism, and peroxisome. The seven biomarkers were positively correlated with neutrophils. Moreover, 8 TFs, 60 miRNAs, and 7 mRNAs formed the TF-miRNA-mRNA regulatory network, including USF1-hsa-mir-1296-5p-AGT and HIF1A-hsa-mir-449a-5p-ACE2. The drug-gene network contained UROKINASE-PLG, ATENOLOL-AGT, and other interaction relationship pairs. Via bioinformatic analyses, the risk of fibrosis and propionate metabolism-related biomarkers in DN were explored, thereby providing novel ideas for research related to DN diagnosis and treatment.

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 , , , and pathogenic 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.

: To evaluate the effectiveness of empagliflozin in reducing all-cause mortality (ACM), hospitalization for heart failure (HHF), myocardial infarction (MI), stroke, cardiovascular mortality (CVM), and end-stage renal disease (ESRD) in routine clinical practice in the Nordic countries of the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) study. : This noninterventional, multicountry cohort study used secondary data from four Nordic countries (Denmark, Sweden, Finland, and Norway). Propensity score (PS) matched (1:1) adults with type 2 diabetes (T2D) initiating empagliflozin (a sodium-glucose cotransporter-2 inhibitor) during 2014-2018 who were compared to those initiating a dipeptidyl peptidase-4 inhibitor (DPP-4i). Cox proportional hazards regression modelling was used to assess the risk for ACM, HHF, MI, stroke, CVM, and ESRD. Meta-analyses were conducted and hazard ratios (HRs) with 95% confidence intervals (CIs) from random-effects models were calculated. : A total of 43,695 pairs of PS-matched patients were identified. Patients initiating empagliflozin exhibited a 49% significantly lower risk of ACM (HR: 0.51, 95% CI 0.40-0.64) compared to DPP-4i. Additionally, empagliflozin was associated with a 36% significantly lower risk of HHF (HR: 0.64, 95% CI 0.46-0.89), a 52% significantly lower risk of CVM (HR: 0.48, 95% CI 0.37-0.63), and a 66% significantly lower risk of ESRD (HR: 0.34, 95% CI 0.15-0.77) compared to DPP-4i. No significant differences were observed in the risk of stroke and MI between patients initiating empagliflozin compared with those initiating a DPP-4i. Results were generally consistent for subgroups (with/without pre-existing CV disease or congestive heart failure) and in sensitivity analyses. : Empagliflozin initiation was associated with a significantly reduced risk of ACM, HHF, CVM, and ESRD compared with initiation of DPP-4i in patients with T2D when examining routine clinical practice data from Nordic countries.

This study elucidated the mechanistic role of (CR) in type 2 diabetes mellitus (T2DM) through bioinformatics analysis and experimental validation. 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 -cells. 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. 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.

No comprehensive meta-analysis has evaluated the efficacy and safety of ertugliflozin compared to a placebo in patients with Type 2 diabetes (T2D) until now. This meta-analysis fills this gap in knowledge. A systematic search was carried out in electronic databases to identify randomized controlled trials (RCTs) that included patients with T2D receiving ertugliflozin in the treatment group and placebo in the control group. The change in HbA1c from the baseline values was the primary outcome, whereas changes in plasma glucose and other metabolic parameters and adverse events (AEs), including hypoglycemia, were the secondary outcomes. Seven RCTs involving 7283 subjects met the inclusion criteria. Ertugliflozin outperformed placebo in reducing HbA1c in both 5 mg (MD -0.62%, 95% CI [-0.80, -0.44], < 0.00001, = 91%) and 15 mg (MD -0.69%, 95% CI [-0.91, -0.47], < 0.00001, = 93%) doses. A higher proportion of patients achieved HbA1c < 7.0% with ertugliflozin than with placebo. Ertugliflozin was also superior to placebo in lowering fasting plasma glucose (FPG), body weight, and systolic and diastolic blood pressure (BP). Ertugliflozin and placebo had comparable AE profiles, including urinary tract infection (UTI) and hypoglycemia, except for the greater risk of genital mycotic infections (GMIs) with ertugliflozin. Ertugliflozin 5 and 15 mg have equivalent efficacy and safety profiles except for greater weight reduction with ertugliflozin 15 mg. Ertugliflozin has a good glycemic efficacy and a reassuring safety profile in managing T2D. Registration number: CRD42023456450.

This study is aimed at investigating health literacy (HL) among diabetes mellitus (DM) patients using a comprehensive, scientific, feasible, and suitable HL assessment indicator system tailored for the diabetic population in mainland China and systematically analyzing the factors influencing HL in this population. The Delphi expert consultation method was employed to initially draft and refine the Diabetes Health Literacy Evaluation Indicator System (DHLEIS). The reliability and representativeness of the indicator system were tested through metrics including the active coefficient, authority degree, and coordination degree. A HL survey questionnaire for diabetic patients was developed based on DHLEIS and administered to diabetic patients across five hospitals in Nantong and Yancheng cities, Jiangsu Province. The random forest method was utilized to deeply analyze the impact of various factors on HL and its four dimensions and to identify the core influencing factors. Analysis of 707 questionnaires based on the DHLEIS revealed that nine factors-age, sex, body shape, income, exercise, education level, duration of DM, whether insulin is injected, and the number of cohabitants-significantly impact the HL levels. Among these, age, duration of DM, education level, and number of cohabitants were particularly influential across the four dimensions of health knowledge, awareness, behavior, and skills. Factors related to health knowledge and skills were the most significant contributors to overall HL. The multidimensional analysis of factors influencing HL offers valuable insights into characterizing varying levels of HL among diabetic patients. This approach supports targeted cognitive improvements and the effective enhancement of health skills, ultimately leading to better health outcomes.