Emerging evidence suggests a link between metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiac arrhythmia. This study aims to investigate the potential relationship between MASLD and atrial fibrillation (AF).

This retrospective cohort study included 8511 participants (age > 65 years) without a history of cardiovascular diseases, cancer, or severe kidney dysfunction. MASLD was diagnosed using hepatic ultrasound in the presence of at least one cardiometabolic risk factor. Poisson regression models were employed to estimate the relative risk (RR) of AF, adjusting for potential confounders.

Participants were categorized into MASLD (n = 3,926) and non-MASLD (n = 4,585) groups. During a mean follow-up period of 3.65 ± 1.20 years, 307 participants with MASLD developed AF, however, the number in the non-MASLD group was 144 (incidence rate 7.82 % vs. 3.14 %). After adjusting for multiple cardiovascular risk factors, MASLD was associated with increased risk of AF (RR = 1.55, 95 %, confidence interval (CI): 1.12-2.13). Positive correlations were observed between age, body mass index (BMI), systolic and diastolic blood pressure, low-density lipoprotein levels, and AF risk. Subgroup analysis revealed a stronger association between MASLD and AF in participants with BMI < 24 kg/m2 (P < 0.01).

This study highlights a significant association between MASLD and an increased risk of developing AF. The elevated risk in patients with MASLD may involve mechanisms extending beyond traditional cardiometabolic factors, particularly in individuals with lower BMI. Further experimental research is warranted to elucidate the underlying pathways linking MASLD and AF.

The liver is vulnerable to damage from environmental pollutants, but evidence on the effects of non-essential metal/metalloid (NEM) mixture on liver function and their mechanisms remains limited. The study aimed to explore the correlations between individual NEMs and their combinations with liver function, and the mediating roles of lipid profiles. The research involved 2642 individuals aged 60 and older in China. Urine concentrations of arsenic (As), cesium (Cs), barium (Ba), thallium (Tl), and cadmium (Cd) were analyzed using ICP-MS. Liver function was assessed based on the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB). To evaluate the individual and combined effects of these NEMs on liver function, linear regression, restricted cubic splines (RCS), weighted quantile sum (WQS), quantile g-computation (QGC), and Bayesian kernel machine regression (BKMR) models were utilized. Mediation analyses were conducted to explore the potential role of lipid profiles in NEM-liver function relations. Adjusted linear regression revealed positive associations of Tl with ALT (β = 0.044, 95 % CI: 0.022 to 0.066) and AST (β = 0.019, 95 % CI: 0.004 to 0.035), and negative associations of Cs (β = -0.015, 95 % CI: -0.020 to -0.010), Tl (β = -0.010, 95 % CI: -0.015 to -0.005), and Cd (β = -0.019, 95 % CI: -0.024 to -0.014) with ALB. The RCS model confirmed these linear relationships. Mixture models consistently demonstrated a positive association between the NEM mixture and ALT/AST, primarily driven by Tl, and a negative association with ALB, predominantly influenced by Cd. Mediation analyses suggested triglycerides and total cholesterol partially mediated the associations between Tl, the NEM mixture, and liver function. In conclusion, the NEM mixture, mainly driven by Tl and Cd, is linked to liver function impairment, with lipid profiles potentially mediating these effects. More research is needed to confirm these findings and clarify the mechanisms.

Non-alcoholic fatty liver diseases (NAFLD), including nonalcoholic steatohepatitis (NASH) and cirrhosis, are strongly associated with insulin resistance and glucose intolerance. Gan-tang-yi decoction (GTYD), as a famous classical prescription effectively reduced the elevated level of blood glucose, and improved insulin resistance in cirrhotic patients. However, its specific chemical compositions and molecular mechanisms are still unclear.

The current study aimed to investigate the active ingredients of GTYD and molecular mechanisms underlying the effect of GTYD against insulin resistance of NASH and cirrhosis.

Active ingredients of GTYD were evaluated by UPLC-Q-TOF/MS in both positive and negative ion modes. The TCMSP database and SwissTarget Prediction database were utilized to identify the major active components and possible targets of GTYD. The diabetes-related targets were screened in the databases of GenCLiP 3, OMIM, and GeneCards. The intersection of these databases was utilized to identify possible GTYD targets for insulin resistance. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Protein-protein interaction (PPI) network and hub target proteins were obtained from the STRING database. The hub targets were validated by RT-qPCR analysis. Furthermore, an insulin-resistant rat model of NASH and cirrhosis was created by subcutaneously injecting CCl4 combined with high fat and high sucrose diet to verify the therapeutic effects and the molecular mechanisms of GTYD in vivo.

A total of 91 compounds were identified from GTYD by UPLC/Q-TOF-MS/MS. After removing duplicates, there were 230 targets associated with both disease and medicines. Targets of GTYD involve many biological processes, such as the positive regulation of cellular metabolic and cellular lipid metabolic processes. KEGG enrichment showed that PI3K/Akt and AGE/RAGE pathways played a prominent role in the treatment. RT-qPCR from the GTYD-treated rats revealed that TNF-α, IL-6, VEGFA, STAT3, IL-1B, and MAPK3 mRNA levels in the insulin resistance of NASH and cirrhosis rats were down-regulated. Up-regulated IRS2/PI3K/Akt and down-regulated AGE/RAGE and MAPK/NF-κB signal pathways were closely related to the therapeutic effect of GTYD against insulin resistance of NASH and cirrhosis rats by biology methods.

GTYD functions as a hepato-protective formula in the insulin resistance of NASH and cirrhosis and exerts its effects via IRS2/PI3K/Akt and AGEs/RAGE signaling pathways.

Metabolic hepatic steatosis (MetHS) is a clinically heterogeneous, multisystemic, dynamic, and complex disease, whose progression is one of the main causes of cirrhosis and hepatocarcinoma. This clinical practice guideline aims to respond to its main challenges, both in terms of disease burden and complexity. To this end, recommendations have been proposed to experts through the Delphi method. The consensus was optimal in recommendations regarding type 2 diabetes as a risk factor (1.5.1, 4.5.1), in which cases early detection of MetHS should be carried out (4.5.2). Its results also emphasize the importance of the use of non-invasive tests (FIB-4, NFS, HFS) for the exclusion of significant fibrosis in patients with suspected MetHS (2.3.1, 2.3.3). Diagnosis should be carried out through the sequential combination of non-invasive indices and transient elastography by FibroScan® for its risk stratification (2.3.3). A nearly unanimous consensus was reached regarding the role of early prevention in the impact on the quality of life and survival of patients (5.1.2), as well as on the effectiveness of the Mediterranean diet and physical exercise in relation to the improvement of steatosis, steatohepatitis and fibrosis in MetHS patients (5.2.2) and on the positive results offered by resmiterom and semaglutide in promoting fibrosis regression (5.4.1). Finally, a great consensus has been reached regarding the importance of multidisciplinary management in MetHS, for which it is essential to agree on multidisciplinary protocols for referral between levels in each health area (6.2.1), as well as ensuring that referrals to Hepatology/Digestive and Endocrinology or Internal Medicine services are effective and beneficial to prevent the risk of disease progression (6.2.3, 6.3.1).

The change in nomenclature from nonalcoholic fatty liver disease to metabolic dysfunction associated-steatotic liver disease has emphasized the importance of metabolic abnormalities in this liver disorder. New pharmacological therapy has recently become available and resmetirom, a thyroid hormone receptor agonist, has received approval for the treatment of non-cirrhotic metabolic dysfunction-associated steatohepatitis and significant liver fibrosis.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by combinations of insulin resistance and insulin deficiency. Non-alcoholic fatty liver disease (NAFLD) is emerging as a public health problem worldwide and affects up to 70% of patients with T2DM. Although patients with T2DM have an increased risk of developing advanced liver disease compared to healthy individuals, varying prevalence rates of NAFLD among patients with T2DM, ranging from 34% to 94%, have been reported.

To determine prevalence and identify associated factors of NAFLD among Limbe patients with T2DM and evaluate correlation with glycemic control.

A cross-sectional study was carried out from February to June 2024 among patients with T2DM. Gamma-glutamyl transferase (GGT) activity and serum triglycerides (TGs) were measured by spectrophotometry. NAFLD was diagnosed using the fatty liver index score. Data were analyzed using SPSS version 26.0 for Windows. Student's t-test was used to compare the means of two groups. The χ 2 test was applied to determine the association of NAFLD and T2DM. Logistic regression analysis was performed to identify predictors of NAFLD. P < 0.05 was considered statistically significant.

Of the 150 patients with T2DM recruited for this study, 63 (58%) were females and the majority (84.7%) had good glycemic control (glycated hemoglobin < 7%). Prevalence of NAFLD among patients with T2DM was 19%. Patients with NAFLD had significantly elevated levels of TGs, GGT, and increased body mass index and waist circumference compared to those without NAFLD. There was a significant association between NAFLD and glycemic control. Predictive factors of NAFLD among patients with T2DM were vegetable intake of less than three times per week [adjusted odds ratio (aOR): 0.131, 95%CI: 0.020-0.839; P = 0.032], central obesity (aOR: 0.167, 95%CI: 0.037-0.748; P = 0.019), and metformin treatment for T2DM (aOR: 0.167, 95%CI: 0.037-0.718; P < 0.001).

The prevalence of NAFLD in patients with T2DM in Limbe Regional Hospital was 19%. Age, central obesity, metformin use, and infrequent consumption of vegetables were important predictors of NAFLD.

(1) Background: Hepatic lipid accumulation is the initial factor in metabolic-associated fatty liver disease (MAFLD) in type 2 diabetics, leading to accelerated liver damage. The NOD-like receptor protein 3 (NLRP3) inflammasome plays a critical role in this process. Dapansutrile (DAPA) is a novel NLRP3 inflammasome inhibitor; however, its effect on ectopic lipid accumulation in the liver remains unclear. This study aimed to investigate the therapeutic effect of DAPA on hepatic lipid accumulation in a diabetic mouse model and its potential mechanisms. (2) Methods: The effects of DAPA on hepatic ectopic lipid deposition and liver function under metabolic stress were evaluated in vivo using db/db and high-fat diet (HFD) + streptozotocin (STZ) mouse models. Additionally, the role and mechanism of DAPA in cellular lipid deposition, mitochondrial oxidative stress, and inflammation were assessed in HepG2 cells treated with free fatty acids (FFA) and DAPA. (3) Results: Our findings indicated that DAPA treatment improved glucose and lipid metabolism in diabetic mice, particularly addressing liver heterotopic lipid deposition and insulin resistance. DAPA treatment also ameliorated lipid accumulation and mitochondrial-related functions and inflammation in HepG2 cells through the NLRP3-Caspase-1 signaling axis. (4) Conclusions: Targeting NLRP3 with DAPA may represent a novel therapeutic approach for diabetes-related fatty liver diseases.

N6-methyladenosine (m6A) is involved in the development of non-alcoholic fatty liver disease (NAFLD). Here, we aimed to investigate the effect of m6A methyltransferase METTL3 on liver damage in high-fat diet (HFD)-induced mouse model and hepatocyte damage treated with free fatty acid (FFA). Plasma lipid, lipogenesis, viability, and apoptosis were measured to assess injury. m6A methylation was evaluated using m6A dot blot, methylated RNA immunoprecipitation, dual-luciferase reporter assay, and RNA decay assay. The results indicated that METTL3 was highly expressed in the liver of HFD mice, which knockdown improved plasma lipid and reduced liver lipids. Additionally, silencing of METTL3 promoted cell viability, inhibited apoptosis, reduced lipid concentrations, and downregulated lipogenesis-related marker levels. Moreover, METTL3 promoted the m6A methylation of FAS and enhanced its stability. In conclusion, silencing of METTL3 attenuates the progression of NAFLD by FAS m6A methylation, suggesting that METTL3 may be a promising target for treating NAFLD.

The acute myocardial infarction (AMI) is a prevalent and severe cardiovascular disease, characterized by its sudden onset, high mortality rate, and unfavorable prognosis. The presence of type 2 diabetes not only signifies a chronic metabolic disorder, but also serves as a catalyst for various cardiovascular and cerebrovascular ailments such as coronary heart disease and stroke. Xining is situated in a region of middle to high altitude and due to its unique geographical environment, coupled with the population's limited health awareness, unequal medical standards and other factors, there remain some AMI patients who are difficult to diagnose early on. The objective of this study is to investigate the efficacy and prognosis of dapagliflozin in patients with acute myocardial infarction complicated by type 2 diabetes in the Xining region.

analysis on January 1, 2018 to January 1, 2020, in Qinghai province people's hospital of cardiovascular internal medicine hospital treatment of 245 cases of acute myocardial infarction combined the clinical data of patients with type 2 diabetes. The patients were divided into dapagliflozin group and control group according to whether they took dapagliflozin during hospitalization. The basic data, laboratory examination indicators and long-term prognosis of the two groups were observed. Follow-up deadline is December 31, 2023, at the end of follow-up, including the primary endpoint and the secondary endpoint.

245 patients were included in this study, age 34-94, the average age (61-11), 200 cases (81.63%) of men, women, 45 cases (18.37%), dapagliflozin group of men 92 cases (77.97%) and control group, 108 cases (85.04%). Two groups of patients' age, gender, diabetes duration, merge disease, echocardiogram and blood biochemical indexes, had no statistical difference (P > 0.05). There were no significant differences in the number of coronary artery lesions, treatment regimens, cardiovascular and hypoglycemic drugs between the two groups (P > 0.05). However, up to dapagliflozin group of patients after discharge significantly lower than the control group, the incidence of cardiovascular adverse events at dapagliflozin group of 4 cases of heart failure and cardiovascular death in 1 case and control group in heart failure 13 cases, 10 cases of cardiovascular death, cerebral hemorrhage 2 cases died. KaplanMeier survival analysis showed that the primary endpoint of survival was significantly higher in the dapagliflozin group than in the control group (P < 0.05). In addition, the overall survival rate of the dapagliflozin group was significantly higher than that of the control group, and the difference was statistically significant (P < 0.05).

Dapagliflozin is safe and reliable in the treatment of patients with acute myocardial infarction and type 2 diabetes, and can effectively reduce the incidence of cardiovascular events and improve the overall survival rate of patients.

This study investigated the ameliorative effects of Yinchen lipid-lowering tea (YCLLT) on Non-alcoholic fatty liver disease (NAFLD), the specific mechanism involved was also studied. We modeled hepatocellular steatosis with HepG2 cells and intervened with different concentrations of YCLLT-containing serum. Lipid deposition was assessed by oil red O staining and AdipoR1 expression was analyzed by Western blot. The hepatocyte steatosis model was further treated with YCLLT-containing serum and/or silencing AdipoR1. Lipid deposition was observed by oil red O staining. Flow cytometry was used to detect apoptosis and mitochondrial membrane potential. The levels of TNF-α, IL-6, MDA, 8-OHdG, and ATP were analyzed by ELISA or the corresponding kits. The mitochondrial structure was observed by transmission electron microscopy. The expression of AdipoR1/AMPK/SIRT1 signaling pathway factors was analyzed by Western blot, and co-localization of SIRT1 and immunofluorescence. The results revealed that YCLLT attenuated lipid deposition, inhibited the levels of inflammatory factors TNF-α and IL-6, reduced the levels of MDA and 8-OHdG, up-regulated the ATP content and mitochondrial membrane potential, and promoted the expression of AdipoR1, p-LKB1, p-AMPKα, SIRT1, and PGC-1a in a cellular model of NAFLD. Further, silencing of AdipoR1 inhibited the ameliorative effect of YCLLT in the NAFLD cell model. Altogether, Yinchen lipid-lowering tea attenuates lipid deposition in a fatty liver model by improving mitochondrial function via activating AdipoR1/AMPK/ SIRT1 signaling.

The relationship between vascular endothelial function and bone mineral density (BMD) in T2DM patients with metabolic dysfunction associated fatty liver (MAFLD) is still unclear. This study aims to analyse the correlation between vascular endothelial function and BMD or fracture risk in T2DM patients with MAFLD.

A total of 872 T2DM patients aged ≥50 years were enrolled and divided into two groups according to the diagnostic criteria of MAFLD: MAFLD (+) and MAFLD (-). Flow-mediated dilation (FMD) was measured by high-resolution ultrasound to reflect vascular endothelial function. BMD was measured by dual-energy X-ray bone densitometry, and FRAX scores were calculated for 10-year hip fracture risk (HF1) and major osteoporotic fracture risk (MOF).

After multivariate adjustment, there was no significant correlation between FMD and BMD in MAFLD (-) group (p > 0.05). In MAFLD (+) and FMD < 4% group, FMD was positively correlated with WB, LS, and FN BMD, while FMD was negatively correlated with fracture risk and osteoporotic fracture history, and this correlation was only observed in female patients. However, FMD was not correlated with BMD and fracture risk and osteoporotic fracture history in 4%≤FMD ≤ 7% and FMD > 7% groups.

The association of FMD with BMD in T2DM patients with MAFLD varies according to FMD level. The decrease of FMD is associated with reduced BMD and increased fracture risk in female patients with FMD < 4% group. FMD may be an influential factor for the occurrence and development of osteoporosis, and has some clinical value in early diagnosis of osteoporosis in T2DM patients with MAFLD.

Diabesity is a pathological condition that combines obesity and type 2 diabetes in the same individual. Due to the current rise in both conditions, the prevalence of diabesity is increasing worldwide. Its etiology is known to be multifactorial; therefore, the aim of this study is to understand how diabesity is associated with various sociodemographic variables, healthy habits, and stress.

A descriptive, cross-sectional study was conducted on 24,224 Spanish workers to evaluate the association between diabesity and various factors such as age, gender, socioeconomic status, smoking, alcohol consumption, physical activity, adherence to the Mediterranean diet, and stress. The criteria used to define diabesity included body mass index (BMI), body fat (BF), and visceral fat (VF).

All the aforementioned variables were found to be associated with diabesity. The highest odds ratios (OR) were observed for age, with values ranging from 5.57 (95% CI: 4.48-6.67) when BF was used as the diabesity criterion to 6.89 (95% CI: 5.60-8.19) when VF was the criterion. Similarly, elevated ORs were observed for male gender, with ORs of 6.77 (95% CI: 5.31-8.24) for VF and 3.34 (95% CI: 2.77-3.94) for BF.

In our study, the profile of a person at highest risk of diabesity is a man over 50 years old from a lower socioeconomic status, who is a smoker, regular alcohol consumer, sedentary, with low adherence to the Mediterranean diet, and experiencing high stress levels.

Diabetes mellitus (DM) is a worldwide epidemic, making it a major non-communicable disease of public health concern. DM is a chronic disease affecting various organs of the body, leading to increased morbidity and frequently causing patients to seek medical care. Patients with DM often suffer from gastrointestinal disturbances, indicating the involvement of the gastrointestinal system (GIS). Common effects on the gastrointestinal tract (GIT) include esophageal dysmotility, gastroesophageal reflux disease (GERD), non-alcoholic fatty liver disease (NAFLD), glycogenic hepatopathy, gastroparesis, and enteropathy. Despite the high rates of GIT complications associated with diabetes, they are often under-recognized by physicians, leading to suboptimal treatment and a poor quality of life for patients. This article reviews the GIT manifestations of DM from the esophagus to the anal canal, including their pathophysiology and current management strategies.

Phytosomal curcumin may have some potential in improving anthropometric indices for nonalcoholic fatty liver disease, and this meta-analysis aims to study the effect of phytosomal curcumin on anthropometric indices for nonalcoholic fatty liver disease.

We have searched several databases including PubMed, EMbase, Web of science, EBSCO and Cochrane library databases, and selected the randomized controlled trials (RCTs) comparing phytosomal curcumin with placebo for nonalcoholic fatty liver disease. This meta-analysis was conducted using the random-effect or fixed-effect model based on the heterogeneity.

Seven RCTs were included in this meta-analysis. Compared with placebo in nonalcoholic fatty liver disease, phytosomal curcumin was associated with substantially reduced body mass index (BMI, mean difference [MD] = -0.72; 95% confidence interval [CI] = -1.11 to -0.33; P = .0003), body fat percent (MD = -2.04; 95% CI = -3.10 to -0.98; P = .0002), weight (MD = -2.15; 95% CI = -3.78 to -0.53; P = .01) and waist circumference (MD = -2.09; 95% CI = -4.05 to -0.12; P = .04), but showed no influence on hip circumference (MD = -0.06; 95% CI = -0.59 to 0.47; P = .83) or waist/hip ratio (MD = 0; 95% CI = -0.01 to 0.01; P = 1).

Phytosomal curcumin is effective to improve anthropometric indices for patients with nonalcoholic fatty liver disease.

In order to take full advantage of traditional Chinese medicine (TCM) and western medicine, combined with machine learning technology, to study the risk factors and better risk prediction model of diabetic retinopathy (DR), and provide basis for the screening and treatment of it. Through a retrospective study of DR cases in the real world, the electronic medical records of patients who met screening criteria were collected. Moreover, Recursive Feature Elimination with Cross-Validation (RFECV) was used for feature selection. Then, the prediction model was built based on Gradient Boosting Machine (GBM) and it was compared with 4 other popular machine learning techniques, including Logistic Regression (LR), K-Nearest Neighbors (KNN), Random Forest, and Support Vector Machine (SVM). The models were evaluated with accuracy, precision, recall, F1 score, and area under the curve (AUC) value as indicators. In addition, grid search was used to optimize the model. To explain the results of the model more intuitively, the Shapley Additive exPlanation (SHAP) method was used. A total of 9034 type 2 diabetes mellitus (T2DM) patients meeting the screening criteria were included in this study, including 1118 patients with DR. 19 features were selected using RFECV in the model construction. We constructed 5 commonly used models, including GBM, LR, KNN, Random Forest, and SVM. By comparing model performance, GBM has the highest accuracy (0.85) and AUC value (0.934), which is the best prediction model. We also carried out hyperparameter optimization of grid search for this model, and the model accuracy reached 0.88, and the AUC value increased to 0.958. Through SHAP analysis, it was found that TCM syndrome types, albumin, low density lipoprotein, triglyceride, total protein, glycosylated hemoglobin were closely related to the increased risk of DR. It can be concluded that TCM syndrome type is the risk factor of DR. The GBM classifier based on grid search optimization, with relevant risk factors of TCM and western medicine as variables, can better predict the risk of DR.

Nonalcoholic fatty liver disease (NAFLD) encompasses a variety of liver conditions impacting individuals who consume minimal or no alcohol. Recently, traditional Chinese medicine has been gradually used to treat mild to moderate fatty liver, among which Dendrobium nobile Lindl. powder has been affirmed by many doctors and patients to be effective. However, there is limited research on combining this treatment with standard therapies for mild to moderate NAFLD.

To survey the effect of combining Dendrobium nobile Lindl. powder with standard treatment on liver function and lipid metabolism disorder in patients with mild to moderate NAFLD.

Eighty patients with mild to moderate NAFLD participated in this retrospective study, classified into two groups: The observation group (n = 40) and the control group (n = 40). In November 2020 and November 2022, the study was conducted at People's Hospital of Chongqing Liang Jiang New Area. The control group received standard treatment, while the observation group received Dendrobium nobile Lindl. powder based on the control group. The study compared differences in traditional Chinese medicine clinical syndrome scores, liver fibrosis treatment, liver function indicators, lipid levels, and serum inflammatory factor levels before and after treatment, and we calculated the incidence of adverse reactions for both groups.

The total effective rate was 97.50% in the observation group and 72.5% in the control group. After 8 weeks of treatment, the main and secondary symptom scores remarkably decreased, especially in the observation group (P < 0.05), and there was a significant reduction in the serum levels of hyaluronic acid (HA), laminin (LN), human rocollagen III (PC III), and collagen type IV (CIV). The levels of HA, LN, PC III, and CIV were significantly lower in the observation group (P < 0.05). After 8 weeks, both groups indicated remarkable improvements in liver function and blood lipid levels, with the observation group having even lower levels (P < 0.05). Serum levels of interleukin-1β, tumor necrosis factor-α, and interleukin-8 also dropped significantly. The observation group had a lower rate of adverse reactions (5.00%) compared to the control group (22.50%).

Adding Dendrobium nobile Lindl. powder to standard treatment has been found to remarkably improve symptoms and reduce inflammation in patients with mild to moderate fatty liver disease. It also enhances hepatic function and lipid profile, ameliorates liver fibrosis indices, and lowers the risk of side effects. Consequently, this therapeutic protocol shows promise for clinical implementation and dissemination.

Several studies have reported associations between specific proteins and type 2 diabetes risk in European populations. To better understand the role played by proteins in type 2 diabetes aetiology across diverse populations, we conducted a large proteome-wide association study using genetic instruments across four racial and ethnic groups: African; Asian; Hispanic/Latino; and European.

Genome and plasma proteome data from the Multi-Ethnic Study of Atherosclerosis (MESA) study involving 182 African, 69 Asian, 284 Hispanic/Latino and 409 European individuals residing in the USA were used to establish protein prediction models by using potentially associated cis- and trans-SNPs. The models were applied to genome-wide association study summary statistics of 250,127 type 2 diabetes cases and 1,222,941 controls from different racial and ethnic populations.

We identified three, 44 and one protein associated with type 2 diabetes risk in Asian, European and Hispanic/Latino populations, respectively. Meta-analysis identified 40 proteins associated with type 2 diabetes risk across the populations, including well-established as well as novel proteins not yet implicated in type 2 diabetes development.

Our study improves our understanding of the aetiology of type 2 diabetes in diverse populations.

The summary statistics of multi-ethnic type 2 diabetes GWAS of MVP, DIAMANTE, Biobank Japan and other studies are available from The database of Genotypes and Phenotypes (dbGaP) under accession number phs001672.v3.p1. MESA genetic, proteome and covariate data can be accessed through dbGaP under phs000209.v13.p3. All code is available on GitHub ( https://github.com/Arthur1021/MESA-1K-PWAS ).

This study aims to validate the efficacy of the conventional non-invasive score in predicting significant fibrosis in metabolic-associated fatty liver disease (MAFLD) and to develop a non-invasive prediction model for MAFLD.

This cross-sectional study was conducted among 7701 participants with MAFLD from August 2018 to December 2023. All participants were divided into a training cohort and a validation cohort. The study compared different subgroups' demographic, anthropometric, and laboratory examination indicators and conducted logistic regression analysis to assess the correlation between independent variables and liver fibrosis. Nomograms were created using the logistic regression model. The predictive values of noninvasive models and nomograms were evaluated using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA).

Four nomograms were developed for the quantitative analysis of significant liver fibrosis risk based on the multivariate logistic regression analysis results. The nomogram's area under ROC curves (AUC) was 0.710, 0.714, 0.748, and 0.715 in overall MAFLD, OW-MAFLD, Lean-MAFLD, and T2DM-MAFLD, respectively. The nomogram had a higher AUC in all MAFLD participants and OW-MAFLD than the other non-invasive scores. The DCA curve showed that the net benefit of each nomogram was higher than that of APRI and FIB-4. In the validation cohort, the AUCs of the nomograms were 0.722, 0.750, 0.719, and 0.705, respectively.

APRI, FIB-4, and NFS performed poorly predicting significant fibrosis in patients with MAFLD. The new model demonstrated improved diagnostic accuracy and clinical applicability in identifying significant fibrosis in MAFLD.

This study aimed to investigate the risk factors and predictors of non-obese fatty liver disease in the Chinese population.

A total of 6,014 adults who underwent physical examinations at Union Hospital of Huazhong University of Science and Technology from March 2019 to March 2023 were included in this study. Fatty liver disease was diagnosed based on at least two of the following criteria: diffuse echo patterns relative to the liver, spleen, and kidney; ultrasonic beam attenuation; and poor intrahepatic visual details. The associations between non-obese fatty liver and gender, age, total bilirubin(TBIL), direct bilirubin(DBIL), alanine aminotransferase(ALT), aspartate aminotransferase(AST), glutamine transferase(GGT), alkaline phosphatase(ALP), triglycerides(TG), total cholesterol(TC), high-density lipoprotein cholesterol(HDLC), low-density lipoprotein cholesterol(LDLC), urea nitrogen(BUN), creatinine(Cr), uric acid(UA), Central nervous system sensitivity PTFQI, TSHI, TT4RI, TFQI, Peripheral sensitivity, free thyroxine(FT4), thyroid-stimulating hormone(TSH), triiodothyronine(FT3), fasting blood glucose(FBG), systolic blood pressure(SBP), diastolic blood pressure(DBP), body mass index(BMI) were analyzed via binary logistic regression. Correlation between non-obese fatty liver and high blood lipids, hypertension, hyperuricemia, diabetes, thyroid dysfunction were analyzed using the Pearson and Spearman methods. ROC curve was used to evaluate the diagnostic effect of the indicator.

Compared with the normal group, age, proportion of males, ALT, AST, GGT, ALP, TG, TC, BUN, Cr, UA, TSHI, TT4RI, FT3/FT4, TSH, FT3, FBG, SBP, DBP and BMI in the disease group were significantly higher. The prevalence of non-obese fatty liver was associated with hyperlipidemia, hypertension, hyperuricemia and diabetes. Gender, age, DBIL, ALT, ALP, TG, HDL-C, LDL-C, BUN, UA, FBG, DBP, BMI were independent risk factors for non-obese fatty liver.FT3/FT4 may be considered as a predictor of nonobese fatty liver.

Risk factors for non-obese fatty liver may include sex, age, TG, TC, BMI, etc. Hyperlipidemia, hypertension, hyperuricemia and diabetes mellitus are related to non-obese fatty liver. FT3/FT4 may be a predictor of non-obese fatty liver disease.

The prevalence of steatotic liver disease (SLD) in patients with type 2 diabetes (T2DM) exceeds 50%. This study aimed to investigate the clinical characteristics of SLD and liver fibrosis in Chinese patients with T2DM.

Inpatients from 2021 to 2023 were included in the study. Fatty liver index (FLI) and fibrosis-4 (FIB-4) were calculated to assess hepatic steatosis and fibrosis respectively. Statistical analysis was completed by SPSS v25 and GraphPad Prism v8.0.1.

Of the 1466 participants, about one-third of the patients in T2DM-SLD group were diagnosed with liver fibrosis (LF), and the percentage of patients over 50 years old was 85.9%. Patients with SLD had higher levels of BMI, blood pressure, liver enzymes, fasting blood glucose (FBG), HbA1c, C-peptide, total cholesterol (TC) and triglyceride (TG) (P<0.05 for all). Patients with liver fibrosis had lower TC, TG, hemoglobin (Hb), erythrocyte count (RBC), leukocyte count (WBC) and platelet (PLT) levels (P<0.05 for all). Compared with simple T2DM and SLD-NLF (non-liver fibrosis) groups, for patients over 50 years old, the prevalence of coronary heart disease, stroke, tumor, and diabetic nephropathy was higher in patients with liver fibrosis. Liver fibrosis might be the risk factor of arterial stiffness, stroke, coronary heart disease and numbness based on multivariable logistic regression analysis.

Hepatic steatosis and fibrosis were common in patients with T2DM. Liver fibrosis was relevant to many macrovascular and microvascular diabetic complications.

Chronic liver disease is a major cause of mortality, with approximately 2 million deaths worldwide each year, and it poses a significant economic burden. The most common cause of chronic liver disease in the United States and Europe is steatotic liver disease (SLD), which includes metabolic dysfunction-associated SLD, metabolic dysfunction and alcohol-associated SLD, and alcohol-associated liver disease (ALD). Effective treatment of these conditions is essential to reduce the liver disease burden, with promising approaches including treating cardiometabolic risk factors and excessive alcohol intake. Glucagon-like peptide 1 receptor agonists, both as monotherapy and in combination with other drugs, are gaining attention for their beneficial impact on cardiometabolic risk factors and excessive alcohol intake. In this review, we examine the molecular and clinical effects of glucagon-like peptide 1 receptor agonists, focusing on their direct hepatic steatohepatitis and liver fibrosis but also the indirect influence on cardiometabolic risk factors and excessive alcohol intake as key features of SLD. We also explore the future implications of glucagon-like peptide 1 receptor agonists for treating metabolic dysfunction-associated SLD, metabolic dysfunction and alcohol-associated SLD, alcohol-associated liver disease, and the potential challenges.

To evaluate the impact of non-alcoholic fatty liver disease (NAFLD) presence and fibrosis risk on adverse outcomes in patients with type 2 diabetes and chronic kidney disease.

Data were sourced from two longitudinal cohorts: 1172 patients from the National Health and Nutrition Examination Survey (NHANES) and 326 patients from the kidney biopsy cohort at the West China Hospital of Sichuan University. Cox regression estimated hazard ratios (HRs) for NAFLD and liver fibrosis concerning adverse clinical outcomes. Subsequently, a two-sample Mendelian randomization study using genome-wide association study statistics explored NAFLD's potential causal link to cardio-cerebrovascular events.

In the NHANES cohort, NAFLD stood as an independent risk factor for various outcomes: overall mortality [HR 1.53 (95% confidence interval, CI 1.21-1.95)], mortality because of cardio-cerebrovascular diseases [HR 1.63 (95% CI 1.12-2.37)], heart disease [HR 1.58 (95% CI 1.00-2.49)], and cerebrovascular disease [HR 3.95 (95% CI 1.48-10.55)]. Notably, advanced liver fibrosis, identified by a fibrosis-4 (FIB-4) score >2.67, exhibited associations with overall mortality, cardio-cerebrovascular disease mortality and heart disease mortality. Within the kidney biopsy cohort, NAFLD correlated with future end-stage kidney disease [ESKD; HR 2.17 (95% CI 1.41-3.34)], while elevated FIB-4 or NAFLD Fibrosis Scores predicted future ESKD, following full adjustment. Liver fibrosis was positively correlated with renal interstitial fibrosis and tubular atrophy in biopsies. Further Mendelian randomization analysis supported a causal relationship between NAFLD and cardio-cerebrovascular events.

In patients with type 2 diabetes and chronic kidney disease, the NAFLD presence and elevated FIB-4 scores link to heightened mortality risk and ESKD susceptibility. Moreover, NAFLD shows a causal relationship with cardio-cerebrovascular events.

Evaluating the safety and efficacy of implanting a liver with islet grafts into patients with end-stage liver disease and diabetes mellitus (DM).

DM and end-stage liver diseases are significant health concern worldwide, often coexisting and mutually influencing each other. Addressing both diseases simultaneously is paramount.

We utilized the islet transplantation combined ischemia-free liver transplantation (ITIFLT) technique to treat a patient with hepatocellular carcinoma (HCC) and type 2 diabetes mellitus (T2DM). The liver was procured and preserved using the ischemia-free liver transplantation (IFLT) technique, and during normothermic machine perfusion (NMP), isolated and purified islet grafts were transplanted into the liver through the portal vein. Finally, the liver, incorporating with the transplant islet grafts, was implanted into the recipient without interruption of blood supply.

The patient received both liver and islet graft from the same donor. The patient achieved insulin-independence by post-transplant day (PTD) 9, and both liver and islet function remained robust. The patient was discharged on PTD 18 and experienced no surgical or transplantation-related complications during the follow-up period. Furthermore, islet grafts presence was observed in liver biopsies after islet transplantation.

This landmark case marks the inaugural application of ITIFLT in humans, signifying its potential as a promising treatment modality for end-stage liver disease with DM.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common chronic liver disease globally, affecting more than a third of the world's adult population. This comprehensive narrative review summarizes the global incidence and prevalence rates of MASLD and its related adverse hepatic and extrahepatic outcomes. We also discuss the substantial economic burden of MASLD on healthcare systems, thus further highlighting the urgent need for global efforts to tackle this common and burdensome liver condition. We emphasize the clinical relevance of early interventions and a holistic approach that includes public health strategies to reduce the global impact of MASLD.

Non-alcoholic fatty liver disease (NAFLD) is a persistent liver condition that affects both human health and animal productive efficiency on a global scale. A number of naturally occurring compounds activate nuclear factor erythroid 2-related factor 2 (Nrf2) as a transcription factor with important protective effects against many liver diseases, including NAFLD. Raffinose (Ra), an oligosaccharide extracted from several plants, exhibits diverse biological functions. However, the uncertainty lies in determining whether the activation of Nrf2 by Ra can provide a preventive effect on liver lipotoxicity.

The aim of this study was to shed light on the molecular pathways by which Ra possesses its protective benefits against NAFLD.

Experimental protocols were established using WT and Nrf2-null (Nrf2-/-) mice. Liver samples from each group were collected for Western blot, RT-qPCR, H & E, Sirius red and Oil red O staining. Additionally, serums were processed for ELISA. ALM12 cells were gathered for Western blot and immunofluorescence. Moreover, to elucidate the molecular mechanism of Ra, molecular docking was performed.

Our results indicated that Ra remarkably alleviated liver lipotoxic in vivo and in vitro. Ra treatment effectively corrected hepatic steatosis, the release of AST, ALT, TG, and TC, as well as the depletion of HDL and LDL. Meanwhile, Ra efficiently prevented inflammation by inhibiting the TLR4-MyD88-NF-κB pathway and pyroptosis. Additionally, these findings implied that Ra reduced the production of fibrosis-related proteins, which enhanced collagen deposition. Molecular docking revealed that Ra possessed the ability to bind specific regions of Nrf2, resulting in the enhancement of Nrf2 activation and nuclear translocation. Ra treatment restored serum redox factors and antioxidant enzymes to normal levels; however, these alterations were clearly reversed in Nrf2-/- mice.

This study reveals novel information on Ra's protective benefits against liver injury caused by abnormal lipid metabolism; these effects are mostly mediated by Nrf2 activation, suggesting a potential new medicine or treatment strategy for NAFLD.

The growing prevalence of non-alcoholic fatty liver disease (NAFLD) in younger populations, particularly those of working age (15-64 years), has become a public health concern. Being diagnosed at a younger age implies a greater likelihood of accruing disability-adjusted life years (DALYs) later in life due to potential progression to conditions such as cirrhosis or hepatocellular carcinoma. This study aims to analyze NAFLD prevalence trends over three decades globally, regionally, and nationally, with a focus on age, period, and birth cohort associations.

Global, regional, and country time trends in the prevalence of NAFLD among working-age people from 1990 to 2019: Age-period-cohort analysis based on Global Burden of Disease Study 2019 estimates and 95% uncertainty interval (UI) of NAFLD prevalence in the working age population was extracted from the Global Burden of Diseases, Injuries and Risk Factors Study 2019. Age-period-cohort models were used to estimate the prevalence within each age group from 1990 to 2019 (local drift, % per year), fitted longitudinal age-specific rates adjusted for period bias (age effect), and period/cohort relative risk (period/cohort effect).

The global age-standardized prevalence (ASPR) of NAFLD increased significantly from 1990 (14,477.6 per 100 000) to 2019 (19,837.6 per 100 000). In the Western Pacific, there were 42,903.8 NAFLD cases in 2019, 54.15% higher than in 1990. The ASPR also increased significantly in the region over the past three decades. At the national level, Palau had the highest ASPR while Brunei Darussalam had the lowest. Age-period-cohort analysis showed that in the Western Pacific, unlike globally, the risk of NAFLD declined after age 60-64 years. Relative to 1980-1989, incidence and DALY risks decreased but prevalence increased in subsequent birth cohorts. Future predictions indicate an upward trend in NAFLD burden, especially among women and medium (SDI) regions like China.

Non-alcoholic fatty liver disease imparts an immense health burden that continues to grow globally and in the Asia Pacific region. Our work highlights working age adults as an at-risk group and calls attention to socioeconomic gradients within Western Pacific countries. Upward future projections demonstrate that NAFLD prevention is an urgent priority.

Type 2 diabetes mellitus (T2DM) increases the risk of non-alcoholic fatty liver disease (NAFLD) progression to advanced stages, especially upon high-fat diet (HFD). HFD-induced hepatic fibrosis can be marked by oxidative stress, inflammation, and activation of hepatic stellate cells. Sirtuin 1/2 (SIRT1/2), NAD-dependent class III histone deacetylases, are involved in attenuation of fibrosis. In our conducted research, TGF-β1-activated LX-2 cells, free fatty acid (FFA)-treated simultaneous co-culture (SCC) cells, and HFD-induced hepatic fibrosis in Zucker diabetic fatty (ZDF) rats, a widely used animal model in the study of metabolic syndromes, were used to evaluate the protective effect of Tenovin-1, a SIRT1/2 inhibitor. ZDF rats were divided into chow diet, HFD, and HFD + Tenovin-1 groups. Tenovin-1 reduced hepatic damage, inhibited inflammatory cell infiltration, micro/ macro-vesicular steatosis and prevented collagen deposition HFD-fed rats. Tenovin-1 reduced serum biochemical parameters, triglyceride (TG) and malondialdehyde (MDA) levels but increased glutathione, catalase, and superoxide dismutase levels. Tenovin-1 mitigated proinflammatory cytokines IL-6, IL-1β, TNFα and fibrosis biomarkers in HFD rats, TGF-β1-activated LX-2 and FFA treated SCC cells. Additionally, Tenovin-1 suppressed SIRT1/2 expression and inhibited JNK-1 and STAT3 phosphorylation in HFD rats and FFA-treated SCC cells. In conclusion, Tenovin-1 attenuates hepatic fibrosis by stimulating antioxidants and inhibiting inflammatory cytokines under HFD conditions in diabetic rats.

This awareness study aimed to determine the ultrasound (US) examination rates in relation to US-confirmed metabolic dysfunction-associated fatty liver disease (MAFLD) diagnosis in internal medicine outpatients with type 2 diabetes (T2D) across Türkiye. A total of 6283 T2D patients were included in this multicenter retrospective cohort study conducted at 17 internal medicine clinics across Türkiye. The presence and indications for US performed within the last 3 years were recorded along with US-confirmed MAFLD rates, laboratory findings on the day of US, and referral rates. Fibrosis-4 (FIB-4) index was calculated to estimate the risk of advanced liver fibrosis (FIB-4 index ≥ 1.3). Overall, 1731 (27.6%) of 6283 patients had US examination, which revealed MAFLD diagnosis in 69.9% of cases. In addition, 24.4% of patients with US-confirmed MAFLD were at risk of advanced fibrosis (FIB-4 index ≥ 1.3), and the referral rate was 15.5%. In conclusion, our findings emphasize an insufficient MAFLD awareness among clinicians and the likelihood of most of T2D patients to be at risk of living with an unknown status regarding their MAFLD and advanced fibrosis risk.

Our study aimed to elucidate the molecular mechanisms underlying NAC1 (nucleus accumbens associated 1) transcriptional regulation of LDHA and its role in HBV immune evasion, thus contributing to the development of cirrhosis and hepatocellular carcinoma (HCC). Utilizing public datasets, we performed differential gene expression and weighted gene co-expression network analysis (WGCNA) on HBV-induced cirrhosis/HCC data. We identified candidate genes by intersecting differentially expressed genes with co-expression modules. We validated these genes using the TCGA database, conducting survival analysis to pinpoint key genes affecting HBV-HCC prognosis. We also employed the TIMER database for immune cell infiltration data and analyzed correlations with identified key genes to uncover potential immune escape pathways. In vitro, we investigated the impact of NAC1 and LDHA on immune cell apoptosis and HBV immune evasion. In vivo, we confirmed these findings using an HBV-induced cirrhosis model. Bioinformatics analysis revealed 676 genes influenced by HBV infection, with 475 genes showing differential expression in HBV-HCC. NAC1 emerged as a key gene, potentially mediating HBV immune escape through LDHA transcriptional regulation. Experimental data demonstrated that NAC1 transcriptionally activates LDHA, promoting immune cell apoptosis and HBV immune evasion. Animal studies confirmed these findings, linking NAC1-mediated LDHA activation to cirrhosis and HCC development. NAC1, highly expressed in HBV-infected liver cells, likely drives HBV immune escape by activating LDHA expression, inhibiting CD8 + T cells, and promoting cirrhosis and HCC development.

Concrete epidemiological evidence has suggested the mutually-contributing effect respectively between nonalcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM), and periodontitis (PD); however, their shared crosstalk mechanism remains an open issue.

The NAFLD, PD, and T2DM-related datasets were obtained from the NCBI GEO repository. Their common differentially expressed genes (DEGs) were identified and the functional enrichment analysis performed by the DAVID platform determined relevant biological processes and pathways. Then, the STRING database established a PPI network of such DEGs and topological analysis through Cytoscape 3.7.1 software along with the machine-learning analysis by the least absolute shrinkage and selection operator (LASSO) algorithm screened out hub characteristic genes. Their efficacy was validated by external datasets using the receiver operating characteristic (ROC) curve, and gene expression and location of the most robust one was determined using single-cell sequencing and immunohistochemical staining. Finally, the promising drugs were predicted through the CTD database, and the CB-DOCK 2 and Pymol platform mimicked molecular docking.

Intersection of differentially expressed genes from three datasets identified 25 shared DEGs of the three diseases, which were enriched in MHC II-mediated antigen presenting process. PPI network and LASSO machine-learning analysis determined 4 feature genes, of which the MS4A6A gene mainly expressed by macrophages was the hub gene and key immune cell type. Molecular docking simulation chosen fenretinide as the most promising medicant for MS4A6A+ macrophages.

MS4A6A+ macrophages were suggested to be important immune-related mediators in the progression of NAFLD, PD, and T2DM pathologies.

Fatty liver disease (FLD) is a highly prevalent pathological liver disorder. It has many and varied etiologies and has heterogeneous clinical course and outcome. Its proper nomenclature and classification have been problematic since its initial recognition. Traditionally, it was divided into two main categories: Alcohol-associated liver disease and nonalcoholic FLD (NAFLD). Among these, the latter condition has been plagued with nomenclature and classification issues. The two main objections to its use have been the use of negative (non-alcoholic) and stigmatizing (fatty) terms in its nomenclature. Numerous attempts were made to address these issues but none achieved universal acceptance. Just recently, NAFLD has received a new nomenclature from an international collaborative effort based on a rigorous scientific methodology. FLD has been renamed steatotic liver disease (SLD), and NAFLD as metabolic dysfunction-associated SLD. Metabolic dysfunction-associated steatohepatitis was chosen as the replacement terminology for non-alcoholic steatohepatitis. This is a significant positive change in the nomenclature and categorization of FLD and will likely have a major impact on research, diagnosis, treatment, and prognosis of the disease in the future.

In this study, we investigated the relationship between sarcopenia and fatty liver in middle-aged and elderly patients diagnosed with type 2 diabetes mellitus (T2DM) to provide a theoretical foundation for the prevention and treatment of sarcopenia.

A total of 282 patients diagnosed with T2DM aged 50 and older and were admitted to the Endocrinology Department of Xin Medical University First Affiliated Hospital between December 2021 and February 2023, were selected. Body mass index (BMI), and limb and trunk muscle mass of the patients were measured, and data were collected. Patients were grouped based on the sarcopenia diagnostic criteria. All study participants underwent the same physical examinations and laboratory tests. The relationship between the onset of sarcopenia and fatty liver in middle-aged and elderly patients diagnosed with T2DM was then investigated using statistical analysis.

Comparing the sarcopenia group to the non-sarcopenia group revealed statistically significant variations in gender, BMI, fatty liver prevalence rate, uric acid (UA), alanine aminotransferase (ALT), blood glucose, blood lipid associated indicators, and limb skeletal muscle content. There were, however, no statistically significant differences in age, disease duration, hypertension, smoking, or alcohol intake. There was a positive correlation between BMI, UA, fasting c-peptide, and Appendicular Skeletal Muscle Index (ASMI). Higher levels of BMI, ASMI, and UA were identified as protective variables against sarcopenia by multifactorial logistic regression analysis.

Higher levels of BMI, ASMI, and UA can greatly reduce skeletal muscle atrophy in patients with T2DM. Patients with a fatty liver may be less vulnerable to sarcopenia. There is little evidence, however, that a fatty liver works as a preventive factor against sarcopenia.

Experimental animal models of diabetes can be useful for identifying novel targets related to disease, for understanding its physiopathology, and for evaluating emerging antidiabetic treatments. This study aimed to characterize two rat diabetes models: HFD + STZ, a high-fat diet (60% fat) combined with streptozotocin administration (STZ, 35 mg/kg BW), and a model with a single STZ dose (65 mg/kg BW) in comparison with healthy rats. HFD + STZ- induced animals demonstrated a stable hyperglycemia range (350-450 mg/dL), whereas in the STZ-induced rats, we found glucose concentration values with a greater dispersion, ranging from 270 to 510 mg/dL. Moreover, in the HFD + STZ group, the AUC value of the insulin tolerance test (ITT) was found to be remarkably augmented by 6.2-fold higher than in healthy animals (33,687.0 ± 1705.7 mg/dL/min vs. 5469.0 ± 267.6, respectively), indicating insulin resistance (IR). In contrast, a more moderate AUC value was observed in the STZ group (19,059.0 ± 3037.4 mg/dL/min) resulting in a value 2.5-fold higher than the average exhibited by the control group. After microarray experiments on liver tissue from all animals, we analyzed genes exhibiting a fold change value in gene expression <-2 or >2 (p-value <0.05). We found 27,686 differentially expressed genes (DEG), identified the top 10 DEGs and detected 849 coding genes that exhibited opposite expression patterns between both diabetes models (491 upregulated genes in the STZ model and 358 upregulated genes in HFD + STZ animals). Finally, we performed an enrichment analysis of the 849 selected genes. Whereas in the STZ model we found cellular pathways related to lipid biosynthesis and metabolism, in the HFD + STZ model we identified pathways related to immunometabolism. Some phenotypic differences observed in the models could be explained by transcriptomic results; however, further studies are needed to corroborate these findings. Our data confirm that the STZ and the HFD + STZ models are reliable experimental models for human T1D and T2D, respectively. These results also provide insight into alterations in the expression of specific liver genes and could be utilized in future studies focusing on diabetes complications associated with impaired liver function.

Non-alcoholic fatty liver disease (NAFLD) is characterized by ectopic deposition of fat in the liver, in the absence of other secondary causes of fat buildup. The relationship between NAFLD, including alanine aminotransferase (ALT), and glycated haemoglobin (HbA1c), is important for predicting the severity of disease and prognosis. This study aims to investigate the association of HbA1c in type 2 diabetes mellitus (T2DM) patients with NAFLD via measuring the ALT levels.

This retrospective cross-sectional study enroled 130 patients with T2DM and NAFLD. The association between levels of HbA1c and ALT in patients of NAFLD with controlled and uncontrolled T2DM, respectively, was investigated. Stratification was done based on gender and diabetic control, using HbA1c levels as a marker of glycemic control. Serum ALT levels were also compared in both groups.

The mean age of the participants was 50.2±5.7 years. The total participants were 130, of which 77 (59.3%) were females and 53 (40.7%) were males. The numbers of patients having uncontrolled T2DM (HbA1c>7%), and controlled T2DM (HbA1c <7%) were 78 (60%) and 52 (40%), respectively. Moreover, 46 (35.3%) females and 32 (24.7%) males had uncontrolled T2DM, and 31 (23.8%) females and 21 (16.2%) males had controlled T2DM. The mean ALT level for uncontrolled and controlled T2DM in female patients was found to be 24.6±3.4 and 13.5±2.4, respectively, (P <0.05). For male patients, it was found to be 54.0±4.9 and 29.1±5.4, respectively (P=0.008).

There is a positive association between elevated HbA1c and ALT levels in T2DM patients with NAFLD.

Detailed investigation of the lipidome remodeling upon normal weight conditions, obesity, or weight loss, as well as the influence of physical activity, can help to understand the mechanisms underlying dyslipidemia in metabolic conditions correlated to the emergence and progression of non-alcoholic fatty liver disease (NAFLD). C57BL/6 male mice were fed a normal diet (ND) or a high-fat diet (HFD) for 20 weeks. Subgroups within the high-fat diet (HFD) group underwent different interventions: some engaged in exercise (HFDex), others were subjected to weight loss (WL) by changing from the HFD to ND, and some underwent a combination of weight loss and exercise (WLex) during the final 8 weeks of the 20-week feeding period. To support our understanding, not only tissue-specific lipid remodeling mechanisms but also the cross-talk between different tissues and their impact on the systemic regulation of lipid metabolism are essential. Exercise and weight loss-induced specific adaptations in the liver and visceral adipose tissue lipidomes of mice were explored by the UPLC-TOF-MS/MS untargeted lipidomics methodology. Lipidomic signatures of ND and HFD-fed mice undergoing weight loss were compared with animals with and without physical exercise. Several lipid classes were identified as contributing factors in the discrimination of the groups by multivariate analysis models, such as glycerolipids, glycerophospholipids, sphingolipids, and fatty acids, with respect to liver samples, whereas triglycerides were the only lipid class identified in visceral adipose tissue. Lipids found to be dysregulated in HFD animals are related to well-established pathways involved in the biosynthesis of PC, PE, and TG metabolism. These show a reversing trend back to basic levels of ND when animals change to a normal diet after 12 weeks, whereas the impact of exercise, though in some cases it slightly enhances the reversing trend, is not clear.

To compare the effects of sodium-glucose co-transporter-2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) on liver function in patients with type 2 diabetes (T2D) in Japan.

This was a Japanese retrospective cohort study using the RWD Database (1 January 2015 to 24 September 2021). Patients newly treated with an SGLT2i or a DPP4i were matched 1:4 (SGLT2i:DPP4i) using propensity score. The primary endpoint was the change from baseline to 1 year after the index date in alanine aminotransferase (ALT). Secondary endpoints included change from baseline in various laboratory test results, including the Fibrosis-4 (FIB-4) index, aspartate aminotransferase, gamma-glutamyl transpeptidase (GGT), albumin and HbA1c. Endpoints were compared between treatment groups using Welch's t-test in the full population and in subgroups stratified by baseline characteristics.

Baseline characteristics of 955 and 3063 matched patients newly treated with an SGLT2i and a DPP4i, respectively, were well balanced. Patients receiving an SGLT2i had significantly greater reductions in ALT, FIB-4 index and GGT and a significantly greater increase in albumin than patients receiving a DPP4i. A significantly greater change from baseline in ALT was observed in the SGLT2i group than in the DPP4i group among subgroups with lower baseline FIB-4 index and HbA1c.

In this study, improvements in various measures, including ALT, the FIB-4 index, GGT and albumin, were observed with SGLT2is compared with DPP4is, suggesting that SGLT2is may provide hepatoprotective benefits, including the prevention of liver fibrosis, in patients with T2D in Japan.