Visceral Fat and Diabetes: Associations With Liver Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Background: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is increasing globally. Noninvasive methods, such as bioelectrical impedance analysis (BIA), which measures body composition, including visceral fat, are gaining interest in evaluating MASLD patients. Our study aimed to identify factors associated with significant liver fibrosis, compare noninvasive scores, and highlight the importance of visceral fat measurement using BIA. Methods: MASLD patients seen in our out-patient department underwent comprehensive evaluations, including liver stiffness using transient elastography, body composition analysis using BIA, and metabolic measurements. Significant fibrosis was defined as a liver stiffness measurement of ≥8.2 kPa. Using multivariate analysis, we identified factors associated with significant liver fibrosis and compared four noninvasive scores with a novel diabetes-visceral fat 15 (DVF15) score. Results: We analyzed data from 609 MASLD patients seen between February 2022 and March 2023. The median age was 43 years (81% male). Among these, 78 (13%) had significant fibrosis. Patients with significant fibrosis had higher rates of type 2 diabetes (41% vs 21%, P < 0.001) and elevated levels of aspartate aminotransferase, alanine aminotransferase, hemoglobin A1c, Fibosis-4, aspartate-aminotransferase-to platelet-ratio index, and NAFLD fibrosis scores. They also exhibited higher visceral and subcutaneous fat. Binary logistic regression revealed type 2 diabetes and a visceral fat level of >15% as associated with significant liver fibrosis. Additionally, the DVF15 score, combining these factors, showed a modest area under the receiver operating characteristic curve of 0.664 (P < 0.001). Conclusion: Our study identified diabetes and high visceral fat as factors associated with significant liver fibrosis in MASLD patients. We recommend that visceral fat measurement using BIA be an essential part of MASLD evaluation. The presence of either diabetes or a visceral fat level of >15% should prompt clinicians to check for significant fibrosis in MASLD patients. Further research is warranted to validate our findings and evaluate the utility of the DVF15 score in larger cohorts and diverse populations.

The association of isocarbophos and isofenphos with different types of glucose metabolism: The role of inflammatory cells.

To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship.

Family model diabetes self-management education and support in faith-based organizations in the Republic of the Marshall Islands: A study protocol.

INTRODUCTION: The Republic of the Marshall Islands (RMI) is an independent nation and a member of the United States (US) Affiliated Pacific Islands through a Compact of Free Association. Health disparities in the RMI are striking, with high rates of type 2 diabetes mellitus (T2DM). The International Diabetes Federation has documented age-adjusted prevalence of T2DM at 23.0 %, compared to the US (13.2 %) and globally (9.8 %). T2DM has a devastating impact on patients and their families. METHODS: The purpose of this article is to present the study protocol for the fully powered two-arm cluster randomized controlled trial using a wait-list control to evaluate the effectiveness of a Family Diabetes Self-Management Education and Support (Family DSMES) program when delivered in a group setting by community health workers (CHWs) in faith-based organizations (FBOs) in the RMI. The study used a community engaged approach, and the study protocol includes adaptations based on the results of our one-arm pilot study. SUMMARY: This study will provide new and innovative information on the effectiveness of Family DSMES delivered in a group setting by CHWs in FBOs in the RMI. The knowledge gained from this research will inform DSMES interventions conducted with Marshallese and other Pacific Islander communities, as well as DSMES interventions conducted in other low-resource countries.

Association between self-care activities and glycemic control among patients with type 2 diabetes mellitus in Northwest Ethiopia general hospitals : a multicenter cross-sectional study.

Diabetes self-care activities are essential for achieving optimal glycemic control. However, little investigation has been conducted in Ethiopia to evaluate the relationship between the rate glycemic controland self-care activities among patients with type 2 diabetes mellitus (T2DM). Therefore, this study was conducted to assess self -care activities and their association with glycemic control among patients with T2DM in Northwest Ethiopia general hospitals. This multicenter cross-sectional study was conducted in Northwest Ethiopia general hospitals diabetic clinics. Diabetes self-care activities were measured using the Amharic version of the Summary of Diabetes Self-Care Activities (SDSCA-Amharic). Glycated hemoglobin (HbA1c) were used to assess the rate of glycemic control. A linear regression model was used to identify predictors of self-care activities and glycemic control. P-value of < 0.05 at 95% confidence interval (CI)  was considerd as statistically significant. Of 413 participants included in the final analysis, two-thirds (66.3%) had poor glycemic control, with a mean HbA1c of 7.94% (SD = 1.75). Blood glucose testing was the most important self-care activity domain for predicting better glycemic control [ß=-0.36, 95% CI (-0.48, -0.24); P = 0.0001] followed by diet [ß=-0.29, 95% CI (-0.39, -0.083); P = 0.0001], foot-care [ß=-0.28, 95% CI (-0.3, -0.061); P = 0.003], and physical activity [ß=-0.27, 95% CI (-0.29, -0.056); P = 0.004], respectively. Moreover, unable to read and write [ß = 0.72, 95% CI (0.57, 3.8); P = 0.037], overweight [ß = 0.32, 95% CI (0.011, 0.62); P = 0.042], obesity [ß = 0.67, 95% CI (0.39, 0.94); P = 0.0001], and low level of medication adherence [ß = 0.7, 95% CI (0.39, 1.1); P = 0.0001] were significant predictors of poor glycemic control.       Previous diabetes education [ß=-0.88, 95% CI (-1.2, -0.57); P=0.0001] was a significant predictor of good glycemic control. The prevalence of poor glycemic control and poor self-care activities were high among patients with T2DM. Self-care activities were independent predictors of glycemic control among patients with T2DM. Therefore, management interventions for patients with T2DM should focus on improving self-care activities and other predictor variables.

The effect of MIND diet on sleep status, anxiety, depression, and cardiometabolic indices in obese diabetic women with insomnia: study protocol for a randomized controlled clinical trial {1}.

BACKGROUND: The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet is a plant-based and anti-inflammatory diet that has the ability to protect and manage cardiovascular and nervous system diseases. Regarding that insomnia and cardiovascular problems are x`common in type 2 diabetes mellitus (T2DM), the present study will assess the effectiveness of the MIND dietary pattern on sleep quality, cardiometabolic indicators, and other psychological indicators. METHODS: Forty-four overweight/obese T2DM women with insomnia, aged 30-65 years, will voluntarily participate in this randomized controlled trial and will be randomized to receive either a MIND low-calorie diet (MLCD) or a low-calorie diet (LCD) over a 3-month period. Before and after the study, sleep quality, some biochemical and cardiometabolic indices, cortisol, brain-derived neurotrophic factor (BDNF), high-sensitivity C-reactive protein (hs-CRP), and oxidative stress indicators will be assessed. DISCUSSION: The use of dietary interventions in the management of T2DM complications is practical and safe. This research seeks to investigate the capacity of the MIND diet in the management of insomnia and cardiovascular problems of DM. It is expected that the results of this research will provide new perspectives on using an ideal dietary regimen to treat these health conditions. TRIAL REGISTRATION: IRCT20181111041611N8. Registered on August 7, 2023. https://www.irct.ir/trial/71772.

Cold Exposure Alleviates T2DM Through Plasma-Derived Extracellular Vesicles.

Purpose: Anecdotal reports have praised the benefits of cold exposure, exemplified by activities like winter swimming and cold water immersion. Cold exposure has garnered acclaim for its potential to confer benefits and potentially alleviate diabetes. We posited that systemic cold temperature (CT, 4-8°C) likely influences the organism's blood components through ambient temperature, prompting our investigation into the effects of chronic cold exposure on type 2 diabetic (T2DM) mice and our initial exploration of how cold exposure mitigates the incidence of T2DM. Methods: The effects of CT (4-8°C) or room temperature (RT, 22-25°C) on T2DM mice were investigated. Mice blood and organ specimens were collected for fully automated biochemical testing, ELISA, HE staining, immunohistochemistry, and immunofluorescence. Glucose uptake was assessed using flow cytometry with 2-NBDG. Changes in potential signaling pathways such as protein kinase B (AKT), phosphorylated AKT (p-AKT), insulin receptor substrates 1 (IRS1), and phosphorylated IRS1 (p-IRS1) were evaluated by Western blot. Results: CT or CT mice plasma-derived extracellular vesicles (CT-EVs) remarkably reduced blood glucose levels and improved insulin sensitivity in T2DM mice. This treatment enhanced glucose metabolism, systemic insulin sensitivity, and insulin secretion function while promoting glycogen accumulation in the liver and muscle. Additionally, CT-EVs treatment protected against the streptozocin (STZ)-induced destruction of islets in T2DM mice by inhibiting ß-cell apoptosis. CT-EVs also shielded islets from destruction and increased the expression of p-IRS1 and p-AKT in adipocytes and hepatocytes. In vitro experiments further confirmed its pro-insulin sensitivity effect. Conclusion: Our data indicate that cold exposure may have a potentially beneficial effect on the development of T2DM, mainly through the anti-diabetic effect of plasma-derived EVs released during cold stimulation. This phenomenon could significantly contribute to understanding the lower prevalence of diabetes in colder regions.

Prevalence of Clinically Significant Liver Fibrosis as Measured by Transient Elastography due to Non-alcoholic Fatty Liver Disease in Indian Individuals with Type 2 Diabetes Mellitus.

Introduction: There is high prevalence of non-alcoholic fatty liver disease in individuals with type 2 diabetes mellitus (T2D), and available evidence suggests higher prevalence of NASH and advanced stages of fibrosis among T2D. Data regarding prevalence of clinically significant liver fibrosis (CSLF) in individuals with T2D is scarce. We investigated the prevalence of transient elastography (TE)-proven CSLF among patients of T2D attending a diabetes clinic at a tertiary care center. Methods: A cross-sectional descriptive evaluation study of 603 consecutive adults with T2D was conducted to detect CSLF using TE. Steatosis was diagnosed using a controlled attenuation parameter >237 dB/m. Results: The prevalence of CSLF was 22.7%, and the prevalence of steatosis was 58.9% in our study. A higher body mass index (BMI) (P = 0.001), aspartate aminotransferase (AST; P = 0.0001), alanine aminotransferase (ALT; P = 0.0001), and low platelets (P = 0.0001) were independent factors associated with CSLF. Elevated ALT and AST (≥40 units/L) levels were present in only 27.7% and 37.2% of individuals with CSLF, respectively. Twenty-six (4.31%) individuals had LSM > 13.0 kPa. Conclusion: CSLF is highly prevalent in T2D patients attending a diabetes clinic at a tertiary care center, and the majority of such individuals have normal transaminase levels. Higher BMI, AST, and ALT values and lower platelet counts are associated with liver fibrosis.

The Association Between Vitamin B12 Deficiency and Diabetic Foot Ulcer in Type 2 Diabetic Patients in Qassim Province, Saudi Arabia: A Case-Control Study.

Background Diabetic foot ulcer (DFU) is a major complication of diabetes with many identified risk factors. These include poor control of diabetes, cardiovascular disease, smoking, and end-stage kidney disease. This study aims to shed light on the micronutrient status of diabetic patients and its effect on DFU, particularly, the association between vitamin B12 deficiency and DFU. Methodology This retrospective case-control study included adults in Buraydah who were at least 18 years old and had type 2 diabetes mellitus. Data were obtained from the electronic files of the patients who visited the diabetes center from January 2018 to August 2023 and were analyzed using SPSS version 27.0.1 (IBM Corp., Armonk, NY, USA). Results The research involved 221 participants, with 114 controls (individuals with diabetes but no DFU), and 107 cases (individuals with diabetes affected by DFU). Vitamin B12 levels varied, with 79.2% falling within the normal range of 187-883 pg/mL. The average age of cases (58.5 years, SD = 11.3) was notably higher than that of controls (54.1 years, SD = 14.1). Glycated hemoglobin levels were significantly higher in cases (8.7, SD = 2.0) compared to controls (7.6, SD = 2.2) (p < 0.001). Regarding physical activity, cases showed a significantly higher percentage of inactivity (62.1%) compared to controls (39.1%) (p = 0.046). Neuropathy exhibited a significant association with ulcer development, with 59.1% of cases having neuropathy compared to 23.5% of controls (p < 0.001). Furthermore, complications such as dry foot and fissures (60.0% vs. 6.3%), Charcot joint (36.8% vs. 12.2%), and foot trauma (40.9% vs. 3.9%) were significantly more prevalent in cases compared to controls (p < 0.001 for all). Conclusions The significant associations observed with advanced age, uncontrolled diabetes, longer diabetes duration, neuropathy, and specific foot complications underscore the multifactorial nature of ulcer development. The normal levels of vitamin B12 in most patients reflect no positive impact of normalized vitamin B12 levels on DFU. However, further observational studies with multiple vitamin B12 readings over a longer period are needed to establish its association with DFU development.

Effectiveness of Multifaceted Lifestyle Interventions in Prediabetic Adults: A Field Study in an Urban Slum Population of Pune, India.

Introduction Adults with diabetes have an increased risk of hypertension, heart attack, and stroke than those without diabetes. Diagnosing prediabetes at an early stage can significantly reduce the risk of diabetes through simple interventions such as lifestyle modifications. Lifestyle modifications such as weight loss combined with regular physical exercise and a healthy diet can help delay or prevent the progression of diabetes. This study aims to estimate the prevalence of prediabetes among the urban slum population and to assess the effect of lifestyle modifications on blood sugar levels, glycated hemoglobin (HbA1c), and lipid profile among the participants. Methods A quasi-experimental field study was conducted among the urban slum population. Participants were randomly selected from previous health screening data. Pre-intervention blood evaluations were performed, and those who fulfilled the criteria were enrolled for interventions. The follow-up period lasted three months and included telephonic and in-person meetings for support and motivation. All variables were reevaluated at the end of the follow-up period. Results Out of 34 participants included in the study, 20 completed the three-month follow-up. Statistically significant changes were observed after three months of intervention in weight, fasting blood sugar, HbA1c, BMI, triglycerides, and high-density lipoprotein (HDL) cholesterol levels. However, decreases in systolic blood pressure (BP), diastolic BP, total cholesterol, and low-density lipoprotein (LDL) cholesterol were not statistically significant. Conclusion The study revealed that lifestyle intervention programs promoting healthy diets, physical activity, and body weight reduction can prevent or delay the onset of diabetes among high-risk populations. The effectiveness of interventions across community settings depends on delivery formats, implementers, and the level of motivation of participants.

Exploring the design of clinical research studies on the efficacy mechanisms in type 2 diabetes mellitus.

This review examines the complexities of Type 2 Diabetes Mellitus (T2DM), focusing on the critical role of integrating omics technologies with traditional experimental methods. It underscores the advancements in understanding the genetic diversity of T2DM and emphasizes the evolution towards personalized treatment modalities. The paper analyzes a variety of omics approaches, including genomics, methylation, transcriptomics, proteomics, metabolomics, and intestinal microbiomics, delineating their substantial contributions to deciphering the multifaceted mechanisms underlying T2DM. Furthermore, the review highlights the indispensable role of non-omics experimental techniques in comprehending and managing T2DM, advocating for their integration in the development of tailored medicine and precision treatment strategies. By identifying existing research gaps and suggesting future research trajectories, the review underscores the necessity for a comprehensive, multidisciplinary approach. This approach synergistically combines clinical insights with cutting-edge biotechnologies, aiming to refine the management and therapeutic interventions of T2DM, and ultimately enhancing patient outcomes. This synthesis of knowledge and methodologies paves the way for innovative advancements in T2DM research, fostering a deeper understanding and more effective treatment of this complex condition.

Alterations of the gut microbiota and metabolites by ShenZhu TiaoPi granule alleviates hyperglycemia in GK rats.

ShenZhu TiaoPi granule (STG) is a compound prescription that is used in Chinese medicine for the treatment of type 2 diabetes mellitus (T2DM). Previous studies have indicated a hypoglycaemic effect, but the underlying mechanism remains unclear. Goto-Kakizaki (GK) rats were used to establish an in vivo T2DM model (Mod). The metformin (Met) and STG treatment time was 12 weeks. Fasting blood glucose (FBG) and insulin levels and the area under the glucose curve (GAUC) were measured. Intestinal pathology and permeability were observed. Microbial diversity analysis and metabolomics were used to investigate the underlying mechanisms. Compared with the Con group, the T2DM Mod group presented significant differences in weight, FBG, GAUC, and homeostasis model assessment-insulin resistance (HOMA-IR) indices (p < 0.01). Met and STG improved these indicators (p < 0.01). The pathological morphology and zonula occludens 1 protein levels in the intestines of the Mod group of rats were altered, leading to increases in the lipopolysaccharide (LPS) and interleukin-1ß (IL-1ß) levels. In the Met and STG groups, the intestinal conditions improved, and the LPS and IL-1ß levels significantly decreased (p < 0.01). Changes in the gut microbiota and metabolites occurred in the Mod group. In the STG group, the abundance of Intestinimonas increased, and the abundance of Eubacterium coprostanoligenes decreased significantly (p < 0.05). Moreover, STG also altered 2-deoxyglucose, beta-muricholic acid and dioxolithocholic acid production. In addition, the main metabolic pathways affected by STG were bile acid biosynthesis and cholesterol metabolism. Intestinimonas, D-maltose_and_alpha-lactose may be potential biomarkers for the effects of STG. STG alleviates hyperglycaemia via the gut microbiota and metabolites in GK rats.

A Study of Psychological Features in Patients With Type 2 Diabetes Mellitus.

AIM: There is a lack of multidisciplinary studies examining the link between psychological factors and glycemic control in individuals with chronic illnesses. The aim of this study is to investigate the relationship between psychological factors such as resilience, perceived stress, emotional regulation, aggressiveness, and glycated hemoglobin (HbA1c) levels in patients with type 2 diabetes. Additionally, the study seeks to determine the predictive value of perceived stress and resilience on HbA1c levels and to explore the role of anger expression and emotion regulation strategies in glycemic control, comparing diabetic patients to healthy controls. MATERIALS AND METHODS: The study was conducted between November 2021 and November 2023 at the Clinic of Endocrinology and Metabolic Diseases at the St. George University Hospital, Bulgaria, and the Department of Science and Research at the Medical University of Plovdiv, Bulgaria. Of these 84 individuals were diagnosed with type 2 diabetes, divided into two groups of 42 individuals each, who had poor and fair glycated hemoglobin. The third group was a healthy control consisting of 42 individuals in the same age group who had no established chronic diseases. RESULTS: When comparing the study groups on HbA1c and individual psychological characteristics, there were statistically significant differences in resilience, perceived stress, emotion regulation suppression, and anger expression. When comparing the mean values of mental resilience with glycated hemoglobin levels, we find that there are statistically significantly higher mean values between the poor HbA1c control and the healthy group. From the regression analysis, we conclude that the psychological characteristics positively associated with perceived stress (ß=0.502; p<0.001) and inversely associated with mental resilience (ß=-0.359; p<0.001) are the most predictive. Less influential was the straight correlation with emotion regulation-expressive inhibition (ß=0.226; p<0.05), the positive correlation with anger (ß=0.170; p<0.001), and general aggressiveness (ß=0.151; p<0.05). CONCLUSION: From the present study, we note that glycated hemoglobin level is strongly influenced by two psychological predictors, namely subjective perception of stressful situations and resilience level.

Hypomethylation at PANDAR promoter progressively induces senescence in adipocyte precursor cells in subjects with obesity and type 2 diabetes.

The risk of developing type 2 diabetes (T2D) is heterogeneous among individuals with obesity. Functional decline of adipocyte precursor cells (APCs) and accumulation of senescent cells in the subcutaneous adipose tissue contributes to the progression toward T2D. LncRNAs regulate cell senescence and may be implicated in determining this abnormality in APCs. Here, we report that APCs from individuals with obesity show a gradual increase in multiple senescence markers, which worsens in parallel with the progression from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) or T2D. Transcriptomic analysis identified PANDAR as the top-ranked lncRNA differentially expressed in APCs from individuals with obesity and T2D and non-obese subjects. Q-PCR confirmed PANDAR up-regulation in APCs from individuals with obesity, at progressively increased levels in those who developed, respectively, IGT and T2D. Bisulfite sequencing and luciferase assays revealed that, in parallel with glucose tolerance deterioration, the -1317 CpG at the PANDAR promoter became hypo-methylated in obesity, resulting in enhanced PANDAR induction by p53. PANDAR silencing in senescent APCs from individuals with obesity and T2D caused repression of senescence programs and cell cycle re-entry. PANDAR transcription in white blood cells (WBCs) mirrored that in APCs. Also, individuals with obesity exhibited rescue of PANDAR transcription in WBCs following bariatric surgery, accompanied by enhanced methylation at the regulatory PANDAR -1317 CpG. In conclusion, PANDAR dysregulation is a newly identified mechanism determining the early senescence of APCs from individuals with obesity, which worsens along the progression toward T2D. In the future, PANDAR targeting may represent a valuable strategy to delay this progression.

Network pharmacology analysis revealed the mechanism and active compounds of Jiao tai wan in the treatment of type 2 diabetes mellitus via SRC/PI3K/AKT signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiao-tai-wan (JTW) is a traditional Chinese herbal prescription, exerts its therapeutic effects on type 2 diabetes mellitus (T2DM). However, its mechanisms and active components remain unclear. AIM OF THE STUDY: To investigate the therapeutic mechanisms of JTW in treating type 2 diabetes mellitus (T2DM), focusing on identifying active components, their targets, and validating efficacy through SRC/PI3K/AKT signaling pathway modulation in vitro and in vivo. MATERIALS AND METHODS: Active ingredients were retrieved from the Traditional Chinese Medicine System Pharmacology (TCMSP) and Comprehensive Traditional Chinese Medicine Database (TCMID). Targets for these components were identified using the ChemMapper database based on 3D structural similarity. T2DM-related genes were sourced from the DisGeNET and Gene Expression Omnibus (GEO) databases. Protein-protein interaction (PPI) analysis and functional enrichment analysis were conducted to construct a pathway network of "herbs-active ingredients-candidate targets", identifying core molecular mechanisms and key active ingredients. SwissDock was used for molecular docking to predict ligands for candidate targets. The diabetic models were established using C57BL/6 mice and human liver HepG2 cell lines. Their Effectiveness and key molecules were verified through biochemical detection and immunoblotting. RESULTS: Total 30 active compounds, 597 active ingredient targets, 9631 T2DM-related genes, and 521 overlapping candidate targets were found for JTW on T2DM. Go enrichment indicated the core pathways enriched on insulin and glucose metabolism. The auto-docking demonstrated SRC has potential binds to ingredients of JTW. In vivo, JTW can reduce blood glucose, and blood lipid levels, and HOMA-IR, and increase HOMA-ISI levels in T2DM mice with reduced ALT, AST, MDA levels and increased SOD levels. Meanwhile, decreased phosphorylation of SRC, along with increased levels of phosphorylated PI3K, PI3K, and phosphorylated AKT, were observed. HE staining of liver tissues further confirmed that JTW administration improved liver morphology, reducing inflammation and necrosis. In vitro, JTW significantly ameliorates upstream dysregulation by reducing SRC phosphorylation while enhancing phosphorylated PI3K, PI3K, and AKT phosphorylation levels. CONCLUSION: JTW may alleviate glucose, insulin resistance, and lipid metabolism disorders by the SRC/PI3K/AKT signaling pathway, that provide a novel view of potential active compounds and essential targets in treating T2DM.

Research on the causal relationship between fine particulate matter and type 2 diabetes mellitus: A two-sample multivariable mendelian randomization study.

BACKGROUND AND AIMS: Previous research has suggested a correlation between fine particulate matter (PM2.5) and type 2 diabetes mellitus (T2DM). However, the causality was vulnerable to confounding variables. METHODS AND RESULTS: A two-sample multivariable mendelian randomization study was designed to examine the causal connection between PM2.5 and T2DM. PM2.5 trait was investigated as exposure while T2DM-related traits as outcomes. The summary data were obtained from the Finngen database and the open genome-wide association study database. The mendelian randomization estimates were obtained using the inverse-variance weighted approach, and multiple sensitivity analyses were conducted. There were potential causal relationships between PM2.5 and T2DM (OR = 2.418; P = 0.019), PM2.5 and glycated hemoglobin (HbA1c) (OR = 1.590; P = 0.041), and PM2.5 and insulin metabolism. PM2.5 was found to have no causal effect on fasting glucose and insulin, 2-h glucose, and insulin-like growth factor binding protein-1 (P > 0.05), while had a potential protective effect against some diabetes complications. CONCLUSIONS: Our findings indicated potential causal relationships among PM2.5 and T2DM, especially the causal relationship between PM2.5 and long-term glucose levels.

Cardiovascular effectiveness of newer glucose-lowering agents, with and without baseline lipid-lowering therapy in type 2 diabetes: A systematic meta-analysis of cardiovascular outcome trials and real-world evidence.

BACKGROUND: Whether the cardiovascular treatment benefits of sodium-glucose co-transporter 2 inhibitors (SGLT-2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) differ by baseline use of statins/lipid lowering therapy is unclear. This systematic review and meta-analysis investigated whether baseline statin use (users vs non-users) influences the cardiovascular and kidney benefits of SGLT-2is and GLP-1RAs in patients with type 2 diabetes (T2D). METHODS: We identified relevant cardiovascular outcome trials (CVOTs) and observational cohort studies from MEDLINE, Embase, the Cochrane Library, and bibliographic searches up to March 2024. The analysis pooled study-specific hazard ratios (HRs) with 95 % confidence intervals (CIs) for outcomes, categorized by baseline statin use status. We also assessed the interactions between these medications and baseline statin use by calculating and pooling the ratio of HRs (RHRs) within each trial. RESULTS: Twenty-five articles (13 articles comprising 6 unique CVOTs and 12 articles comprising 9 unique cohort studies) were eligible. In CVOTs of SGLT-2is, the HRs (95 % CIs) of MACE; composite of CVD death or hospitalisation for heart failure; stroke; and kidney events in statin users were 0.90 (0.82-1.00), 0.78 (0.60-1.02), 1.00 (0.77-1.31), and 0.60 (0.53-0.69), respectively. The corresponding estimates were similar in non-statin users. In CVOTs of GLP-1RAs, the HRs (95 % CIs) for MACE in statin and non-statin users were 0.81 (0.73-0.90) and 0.92 (0.77-1.11), respectively. In observational cohort studies, SGLT-2is similarly reduced the risk of several cardiovascular and kidney outcomes in both statin and non-statin users. The estimated RHRs and p-values for interaction indicated that baseline statin use status did not significantly modify the cardio-kidney benefits of SGLT-2is and GLP-1RAs. CONCLUSIONS: Aggregate analyses of intervention and real-world evidence show that SGLT-2is and GLP-1RAs provide comparable cardio-kidney benefits in patients with T2D, regardless of baseline statin use status. PROSPERO Registration: CRD42024498939.

Effect of probiotics on glycemic control and lipid profiles in patients with type 2 diabetes mellitus: a randomized, double blind, controlled trial.

Introduction: This double-blind, placebo-controlled, randomized (1:1) clinical trial was conducted at the West China Hospital, Sichuan University, from March to September 2017. Methods: Eligible participants included adults aged 18 years and older, living in the community, diagnosed with type 2 Diabetes Mellitus according to ADA guidelines, capable of self-managing their diabetes, and able to visit the study site for follow-up. The intervention group received 25 ml of a probiotic beverage containing with over 10^8 CFU/mL of Lactobacillus, administered four times daily. An equal volume of inactivated Lactobacillus was administered to the control group and the control group was administered the same volume of inactivated Lactobacillus. This study aimed to evaluate the effectiveness of probiotics on glycemic control and other diabetes-related outcomes in patients with type 2 diabetes patients. The primary outcomes were changes in HbA1c and FBG levels post-intervention. Investigators, participants, and study site personnel were blinded to the treatment allocation until the conclusion of the study. This double-blind, randomized, placebo-controlled clinical trial was registered in the Chinese Clinical Trial Registry (ChiCTR-POR-17010850). Results: Of the 490 participants screened, 213 were randomized to either the probiotics group (n = 103) or the placebo group (n = 110). After 16 weeks of follow-up, the probiotic group showed reductions in HbA1c [-0.44 (-0.66 to -0.22)] and FBG [-0.97 (-1.49 to 0.46)] post-intervention, similar to the placebo group with reductions in HbA1c [-0.33 (-0.52 to -0.15)] and FBG [-0.90 (-1.32 to -0.47)], but these changes were not statistically significant in PP and ITT analyses (P>0.05). Adverse events were similarly distributed among groups, indicating comparable safety profiles. Discussion: Overall, 16-week probiotic supplementation showed no beneficial effects on glycemic control, lipid profiles, or weight. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=18421, identifier ChiCTR-POR-17010850.

Assessment of correlation between lipid ratios and body mass index in patients with type 2 diabetes mellitus in Sarajevo, Bosnia and Herzegovina.

Objective. Studies that have evaluated correlation between body mass index (BMI) and novel lipid indices such as triglycerides (TG)/high-density lipoprotein-cholesterol (HDL-C), total cholesterol (TC)/HDL-C, and low-density lipoprotein cholesterol (LDL-C)/HDL-C in type 2 diabetes mellitus (T2DM) are scarce. Hence, the aim of the present study was to explore the correlation between BMI and novel lipid indices in Bosnian patients with T2DM. Methods. Present study included 117 patients with T2DM (mean age: 66.51 years) and 68 controls (mean age: 68.37 years). BMI was calculated as weight/height². Lipids were measured by standard methods. TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C ratios were separately calculated. The differences between the groups were assessed by Student's t-test or Man Whitney U test. Correlations were determined by Spearman's test. Results. In a total sample of T2DM patients, 41.0% were overweight and 44.4% were obese. In the control group, 51.5% of subjects were overweight and 25.0% were obese. In T2DM group, a significant correlation was observed between BMI and HDL-C, LDL-C, TG/HDL, TC/HDL-C, and LDL-C/HDL-C ratios. In the control group, there was a significant correlation found between BMI and HDL-C, TG, TG/HDL, TC/HDL-C, and LDL-C/HDL-C-ratios. Correlation between BMI and other lipid parameters in T2DM and the control group was not determined. Conclusion. The present study showed significant correlation between BMI and novel lipid indices in both T2DM patients and the control group of subjects. Possible explanation for the observed results might be prevalence of overweight and obese participants in this study sample. Since novel lipid indices are used in the prediction of cardiometabolic risk, results obtained in the present study have valuable clinical implications.

Loneliness, Discrimination, Stress and Type 2 Diabetes Risk in Young Adults.

INTRODUCTION: The aim of this study was to determine the associations between type 2 diabetes (T2D) or prediabetes and loneliness and related social experiences in young adults, a population at increasingly high risk of T2D. METHODS: This was a cross-sectional analysis using data from adults ages 18-35 enrolled in the All of Us Research Program. Exposures included loneliness, social support, discrimination, neighborhood social cohesion, and stress, measured by standardized surveys. The main outcome was T2D or prediabetes by self-report or linked health record. Logistic regression determined odds of T2D/prediabetes for each survey measure, adjusting for age, sex, race or ethnicity, income, and family history. Latent class analysis (LCA) evaluated clustering of social experiences. Data was collected from 2018-2022 and analyzed May 2023-June 2024. RESULTS: The cohort included 14,217 young adults (28.2 ± 4.4 years; 70.3% (n=9,792) women; 64.1% (n=9,111) White, 10.6% (n=1,506) Hispanic, 5.7% (n=806) Black, 9.1% (n=1,299) multiracial). Overall, 5.5% (n=777) had either prediabetes or T2D. The two highest loneliness quartiles were associated with increased odds of prediabetes/T2D (Q3: OR 1.42 [95% CI 1.15-1.76]; Q4: 1.75 [95% CI 1.43-2.16]). Greater stress and discrimination and lower social support and neighborhood social cohesion were also associated with increased odds of prediabetes/T2D. LCA revealed three distinct phenotypes, with elevated odds of prediabetes/T2D in the two with the most adverse social profiles (OR 2.32 [95% CI 1.89-2.84] and OR 1.28 [95% CI 1.04-1.58]). CONCLUSIONS: Loneliness and related experiences are strongly associated with T2D and prediabetes in young adults. Whether these factors could be leveraged to reduce T2D risk should be investigated.

New insights on genetic background of major diabetic vascular complications.

BACKGROUND: By 2045, it is expected that 693 million individuals worldwide will have diabetes and with greater risk of morbidity, mortality, loss of vision, renal failure, and a decreased quality of life due to the devastating effects of macro- and microvascular complications. As such, clinical variables and glycemic control alone cannot predict the onset of vascular problems. An increasing body of research points to the importance of genetic predisposition in the onset of both diabetes and diabetic vascular complications. OBJECTIVES: Purpose of this article is to review these approaches and narrow down genetic findings for Diabetic Mellitus and its consequences, highlighting the gaps in the literature necessary to further genomic discovery. MATERIAL AND METHODS: In the past, studies looking for genetic risk factors for diabetes complications relied on methods such as candidate gene studies, which were rife with false positives, and underpowered genome-wide association studies, which were constrained by small sample sizes. RESULTS: The number of genetic findings for diabetes and diabetic complications has over doubled due to the discovery of novel genomics data, including bioinformatics and the aggregation of global cohort studies. Using genetic analysis to determine whether diabetes individuals are at the most risk for developing diabetic vascular complications (DVC) might lead to the development of more accurate early diagnostic biomarkers and the customization of care plans. CONCLUSIONS: A newer method that uses extensive evaluation of single nucleotide polymorphisms (SNP) in big datasets is Genome-Wide Association Studies (GWAS).