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.

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.

Random C-Peptide and Islet Antibodies at Onset Predict ß Cell Function Trajectory and Insulin Dependence in Pediatric Diabetes.

CONTEXT: Identification of prognostic biomarkers in pediatric diabetes is important for precision medicine. OBJECTIVE: We assessed whether C-peptide and islet autoantibodies are useful to predict the natural history of children with new-onset diabetes. METHODS: We prospectively studied 72 children with new-onset diabetes (median follow-up: 8 months) by applying the Aß classification system ("A+": islet autoantibody positive, "ß+": random serum C-peptide≥1.3 ng/mL at diagnosis). Beta-cell function was assessed longitudinally with 2h post-prandial/stimulated urinary C-peptide-to-creatinine ratio (UCPCR) 3-12 weeks (V1) and 6-12 months after diagnosis (V2). We obtained a type 1 diabetes genetic risk score (T1D GRS2) for each participant, and compared characteristics at baseline, and clinical outcomes at V2. RESULTS: The cohort was 50% male. Racial distribution was 76.4% White, 20.8% Black and 2.8% Asian or other races. A total of 46.5% participants were Hispanic. Median age (Q1-Q3) was 12.4 (8.3-14.5) years. The Aß subgroup frequencies were 46 A+ß-(63.9%), 1 A-ß-(1.4%), 4 A+ß+(5.6%), and 21 A-ß+(29.2%). Baseline serum C-peptide correlated with UCPCR at both V1 (r=0.36, p=0.002) and V2 (r=0.47, p<0.001). There were significant subgroup differences in age, race, frequency of diabetic ketoacidosis and T1D GRS2 (p<0.01). At V2, the two ß- subgroups had lower UCPCR and higher HbA1c compared with the two ß+ subgroups (p<0.001 and p=0.02, respectively). Thirty-eight percent of A-ß+ but none of the other subgroups were insulin-independent at V2 (p<0.001). CONCLUSIONS: C-peptide and islet autoimmunity at diagnosis define distinct phenotypes and predict beta-cell function and insulin dependence 6-12 months later in racially/ethnically diverse children with new-onset diabetes.

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.

Obese have comparable ankle brachial pressure index but higher ß-cell function and insulin resistance as compared to normal-weight type 2 diabetes mellitus patients.

OBJECTIVES: To compare ankle brachial pressure index (ABPI) in normal weight and obese/overweight type 2 diabetes mellitus patients (T2DM) to see the impact of obesity on the occurrence of peripheral artery disease (PAD) in T2DM patients. Secondly to investigate the relationship between ABPI, insulin resistance, and beta cell function and between adipocytokines and obesity parameters. METHODS: A total of 120 BMI-categorized Normal weight (NW) T2DM (n = 53) patients and obese/overweight T2DM (n = 67) patients were recruited in this study. ABPI measurements were performed for the assessment of PAD. The anthropometry and body composition of the patients were measured. Plasma fasting insulin, adiponectin, and IL-6 levels were measured by ELISA kits. RESULTS: ABPI scores were found to be comparable between both groups of patients (p = 0.787). A significant positive correlation was observed between ABPI and beta cell function. Insulin resistance was found to correlate positively while adiponectin negatively with obesity parameters. CONCLUSION: The ABPI score was comparable between both groups of patients, suggesting that vascular complications may occur at the same rate in NW as well as in obese/overweight diabetic patients. The positive association of insulin resistance as well as the negative association of adiponectin with obesity parameters, are suggestive of the importance of body fat distribution in predicting insulin resistance and the inflammatory status of the cells.

Zein nanoparticles extend lifespan in C. elegans and SAMP8 mice.

Empty zein nanoparticles (NP) have been shown to lower glycemia in rats by stimulating the secretion of endogenous GLP-1. This study evaluated the effect of these nanoparticles on the lifespan of two animal models: C. elegans fed with a glucose-rich diet and the senescence accelerated mouse-prone 8 (SAMP8 mice). In C. elegans, NP increased the mean lifespan of worms by 7 days (from 17.1 for control to 24.5 days). This observation was in line with the observed significant reductions of glucose and fat contents, lipofuscin accumulation, and ROS expression. Furthermore, NP supplementation led to an upregulation of the expression of daf-16 and skn-1 genes. DAF-16 (orthologue of the FOXO family) and SKN-1 (orthologue of mammalian Nrf/CNC proteins) are implicated in activating detoxification mechanisms against oxidative damage. In SAMP8, oral administration of NP also extended the mean lifespan of mice (by 28 % compared to controls), corroborating the protective effect of these nanoparticles.

Involvement of Single Nucleotide Variants in the Klotho Gene Among Obesity Individuals with and without Type 2 Diabetes Mellitus in the Saudi Population.

Purpose: Aging is characterized by the gradual physiological changes and alterations that accumulate over time in the human body. The combination of obesity and ageing can lead to an increased risk of serious health issues or death. Single nucleotide variants (SNVs) in the Klotho gene were commonly studied, including that in type 2 diabetes mellitus (T2DM). Aim: The aim of this study is to examine the possible effect of SNVs in Klotho on the obese population in Saudi Arabia using middle-aged participants with and without T2DM. Methods: This study consists of 100 controls and 100 obesity patients, in which 50 had T2DM and the remaining 50 were obese without T2DM. Genotyping was performed with PCR, and Sanger sequencing analysis was used to validate the molecular association. Results: In this study, rs1207568 (p = 0.001-0.003) and rs9527025 (p = 0.001-0.00004) SNVs were associated with obesity cases. However, none of the genotypes or allele frequencies showed a positive association with the rs564481 SNV (p = 0.344-0.881). The multiple linear regression model showed that waist and hip were associated (p = 0.01-0.02). ANOVA analysis showed age (p = 0.04), hip (p = 0.002), SBP, and TC (p = 0.02) were associated. Finally, SNV (rs1207568 and rs95270250) and obesity (p < 0.001) associations were confirmed through gene multifactor dimensionality reduction analysis with gene-gene interaction, dendrogram, and graphical depletion method. Conclusion: This study concludes that rs1207568 and rs9527025 SNVs are associated with obesity in the Saudi population. Additional genetical statistics showed significant association between dependent and independent variables. SNVs in Klotho play a role in the Saudi population's susceptibility to obesity.

Design, synthesis and enzymatic inhibition evaluation of novel 4-hydroxy Pd-C-â ¢ derivatives as α-glucosidase and PTP1B dual-target inhibitors.

A library of 4-Hydroxy Pd-C-Ⅲ derivatives (5a-5p and 8a-8h) as α-glucosidase inhibitors was prepared and the activity of these compounds against α-glucosidase was evaluated. The outcomes displayed that most of the derivatives had moderate to potent α-glucosidase inhibition with IC50 values ranging from 66.3 ± 2.4 to 299.7 ± 6.0 µM. Amongst these compounds, 8a had the strongest α-glucosidase inhibition than others with an IC50 value of 66.3 ± 2.4 µM. Therefore, 8a was chosen to detect the inhibitory activities on PTP1B and α-amylase, the results revealed that 8a had the potential to be PTP1B (IC50 = 47.0 ± 0.5 µM) and α-amylase (IC50 = 30.62 ± 2.13 µM) inhibitor. Additionally, the enzyme kinetic study displayed that 8a was a mixed-type inhibitor. Moreover, the results of the spectroscopy experiments proved that 8a could quench the fluorescence intensity of α-glucosidase in a dose-dependent manner, destroy the secondary structure of α-glucosidase and change the conformation of the enzyme. Significantly, the investigation of cellular thermal shift assay exhibited that 8a could target the PTP1B protein, and the in vitro cytotoxicity discovered compound 8a had no significant toxicity to normal HEK-293 cells. Additionally, the results of molecular docking found that 8a could both bind the active sites of the α-glucosidase and PTP1B. Importantly, the in vivo sucrose-loading test displayed 8a had potential to reduce the postprandial blood glucose. All results proved that compound 8a had great potential as a dual-target inhibitor in treating Type 2 diabetes mellitus.

A discrete choice experiment to understand preferences of patients with type 2 diabetes about the attributes of GLP1 receptor agonists in Spain.

OBJECTIVE: To determine the preferences regarding injection, medication frequency and complexity of GLP1 receptor agonists among patients with type 2 diabetes, treatment-naïve for such drugs in Spain. Additionally, patients' willingness to pay according to these attributes was evaluated. METHODS: A discrete-choice experiment survey designed to evaluate patients' preferences over three attributes discriminating by age, sex and patients experience with previous injectable treatment was fulfilled by patients. The resulting model was analyzed using a conditional (fixed-effects) logistic regression. RESULTS: A total of 180 patients (63.35 ± 11.49 years, 63.28% men, 48.41% with previous cardiovascular disease, 54.69% with a time of evolution of diabetes >10 years) recruited from 5 health care centers in Spain completed the survey. Patients viewed positively weekly injections (vs daily injections), but rated negatively a complex preparation of the dose (vs simple preparation). Whereas naïve patients for injectable medications did not consider administration timing of importance, no naïve patients considered it relevant. No relevant differences were observed according to age or gender. Patients were willing to pay 83.25€for a "no preparation required" dose. No naïve and naïve patients were willing to pay 34.61€ and 14.35€; p = 0.000, to change daily injection for a weekly injection. CONCLUSIONS: Patients highly valued the avoidance of injections, with weekly dosing clearly preferred over daily dosing, as well as reducing the treatment complexity. These findings may provide a better understanding of what patients prefer and value in their treatment and provide guidance for clinicians making therapeutic decisions regarding treatments of patients with type 2 diabetes.

Short term sodium glucose transport protein 2 inhibitors are associated with post contrast acute kidney injury in patients with diabetes.

Although sodium-glucose transport protein-2 (SGLT2) inhibitors (SGLT2i) do not increase the risk of acute kidney injury (AKI) in general, they may pose a risk in patients undergoing angiography. This prospective cohort study aimed to evaluate the safety and efficacy of SGLT2i for post-contrast AKI (PC-AKI) in patients with type 2 diabetes mellitus (T2DM). Following screening, 306 patients with T2DM selected to undergo coronary arterial angiography with or without percutaneous intervention were enrolled. Patients were divided into the SGLT2i exposure and non-exposure groups. The primary outcome was PC-AKI, defined as an increase in serum creatinine levels > 0.5 mg/dL (44.2 µmol/L), or 25% above the baseline, within 48-72 h after exposure to contrast medium. The incidence of PC-AKI in the overall T2DM population was 5.2% (16/306). Following 1:1 propensity score matching, the incidence of PC-AKI was significantly higher in the SGLT2i group than in the non-SGLT2i group (10.7% vs. 2.9%; P = 0.027), with an odds ratio of 4.5 (95% confidence interval: 1.0-20.2; P = 0.047). Furthermore, PC-AKI occurred at a higher rate among short-term users of SGLT2i than long-term users (20.5% vs. 3.4%, P = 0.018). Thus, our findings suggest an increased risk of PC-AKI associated with short-term SGLT2i therapy in patients with T2DM.

Enhancement of Subcutaneous Islet Transplant Performance by Collagen 1 Gel.

Human islets can be transplanted into the portal vein for T1 diabetes, and a similar procedure is being used in a clinical trial for stem cell-derived beta-like cells. Efforts have been underway to find an alternative transplant site that will foster better islet cell survival and function. Although conceptually attractive, the subcutaneous (SC) site has yielded disappointing results, in spite of some improvements resulting from more attention paid to vascularization and differentiation factors, including collagen. We developed a method to transplant rat islets in a disk of type 1 collagen gel and found improved efficacy of these transplants. Survival of islets following transplantation (tx) was determined by comparing insulin content of the graft to that of the pre-transplant islets from the same isolation. At 14 days after transplantation, grafts of the disks had more than double the recovered insulin than islets transplanted in ungelled collagen. SC grafts of disks had similar insulin content to grafts in a kidney site and in epididymal fat pads. In vivo disks underwent contraction to 10% of initial volume within 24 h but the islets remained healthy and well distributed. Whole mount imaging showed that residual donor vascular cells within the islets expanded and connected to ingrowing host blood vessels. Islets (400 rat islet equivalents (IEQ)) in the collagen disks transplanted into an SC site of NOD scid IL2R gammanull (NSG) mice reversed streptozotocin (STZ)-induced diabetes within 10 days as effectively as transplants in the kidney site. Thus, a simple change of placing islets into a gel of collagen 1 prior to transplantation allowed a prompt reversal of STZ-induced diabetes using SC site.

Cardiovascular outcomes with exenatide in type 2 diabetes according to ejection fraction: The EXSCEL trial.

AIMS: Glucagon-like peptide-1 receptor agonists reduce major adverse cardiovascular events (MACE) and cardiovascular mortality in people with type 2 diabetes (T2D). However, previous studies suggest the effects on heart failure outcomes vary according to left ventricular ejection fraction (LVEF). We aimed to evaluate the effects of exenatide on cardiovascular events according to LVEF in people with T2D. METHODS AND RESULTS: Post-hoc analysis of the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial evaluating the effects of once-weekly exenatide (EQW) versus placebo on cardiovascular outcomes according to baseline LVEF (<40% or ≥40%). Outcomes were also evaluated according to New York Heart Association (NYHA) class and obesity. The main outcome was hospitalization for heart failure (HHF). A treatment-by-LVEF interaction was used. In EXSCEL (n = 14 752), 4749 participants had LVEF available at baseline; 455 (10%) with LVEF <40%, 4294 (90%) with LVEF ≥40%. LVEF modified the EQW effect on hHF: hazard ratio (HR) = 1.52 (95% confidence interval [CI] = 0.95-2.43) in participants with LVEF < 40% and HR = 0.74 (95% CI = 0.55-1.01) in those with LVEF ≥ 40% (p-interaction = 0.012). No significant treatment-by-LVEF interactions (p-interaction >0.10) were observed for MACE, cardiovascular death or all-cause mortality. The risk of HHF was also modified by baseline NYHA class (HR 0.91, 95% CI 0.65-1.27 for NYHA class I/II; HR 1.84, 95% CI 0.95-3.59 for NYHA class III/IV; p-interaction = 0.062), mostly driven by the LVEF <40% subgroup. Obesity did not modify the effects of EQW on HHF. CONCLUSIONS: The EQW effect on HHF was influenced by LVEF, with a potentially decreased risk in participants with LVEF ≥40% and increased risk in those with LVEF <40%. The risk of HHF was particularly high in participants with LVEF <40% and NYHA class III/IV. LVEF did not modify the effect of EQW on atherosclerotic outcomes.

Glycaemic outcomes in adults with type 2 diabetes over 34 weeks with the Omnipod® 5 automated insulin delivery system.

AIMS: The aim was to evaluate the effect of extended use of the Omnipod® 5 automated insulin delivery (AID) system in adults with type 2 diabetes and suboptimal glycaemic control. MATERIALS AND METHODS: Following an 8-week single-arm, multicentre, outpatient trial of AID in adults with type 2 diabetes and baseline ≥ 64 mmol/mol, participants were given the opportunity to continue use of the AID system in a 26-week (~6 month) extension phase. The primary safety endpoints were percentage of time with sensor glucose ≥ 250 mg/dL and < 54 mg/dL. Additional glycaemic measures, including percentage of time in range (TIR) (70-180 mg/dL) and HbA1c, were evaluated. The use of non-insulin anti-hyperglycaemic medications was permitted throughout the entire study. RESULTS: During the initial 8-week study, participants (N = 22) achieved a decrease in percentage of time ≥ 250 mg/dL from 27.4% ± 21.0% to 10.5% ± 8.8% (p < 0.0001), which further decreased to 9.7% ± 9.2% during the extension phase (p = 0.0002 vs. standard therapy). Percentage of time < 54 mg/dL remained low from standard therapy through extension (median [interquartile range] 0.00% [0.00%, 0.06%] vs. 0.02% [0.00%, 0.05%], p > 0.05). HbA1c decreased by 1.6% ± 1.2% (15.5 ± 13.1 mmol/mol, p < 0.0001) and TIR increased by 22.4% ± 19.2% (p < 0.0001) from standard therapy through extension with no significant change in body mass index and without an observed increase in total daily insulin requirements. CONCLUSIONS: These longer-term findings of Omnipod 5 AID system use demonstrate the potential value of AID in helping people with type 2 diabetes reach glycaemic targets.

Metabolic-Bariatric Surgery Reduces Pancreatic Cancer Risk: A Meta-Analysis of Over 3.7 Million Adults, Independent of Type 2 Diabetes Status.

AIMS: To investigate the impact of Metabolic-Bariatric surgery (MBS) on pancreatic cancer (PCa) risk in individuals with obesity based on type 2 diabetes(T2D) status. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines (PROSPERO: CRD42022367749). The primary outcomes were the PCa incidence rates in participants with or without T2D who underwent MBS compared with the control (non-MBS) group. Subgroup analyses based on the MBS types were performed and a random-effects model was employed. Sensitivity analysis was conducted by applying the leave-one-out meta-analysis technique and excluding studies with a short follow-up. Heterogeneity was evaluated using the I2 index and Cochran's Q test. Publication bias was assessed with Egger's test and the risk of bias was assessed with the Cochrane Risk-of-Bias tool. RESULTS: Twelve studies, with 3,711,243 participants, were included. PCa risk was lower in the MBS group for both T2D and the overall population than in the non-MBS group (RR = 0.46, 95% CI: 0.30-0.71 and RR = 0.21; 95% CI: 0.07-0.57, respectively), with consistent findings after excluding studies with < 3-year follow-up. A favourable impact was also observed in individuals without T2D (RR = 0.56, 95% CI: 0.41-0.78). When comparing the types of MBS versus control, a significant difference was observed for sleeve gastrectomy (SG) (RR = 0.24; 95% CI, 0.12-0.46 for SG and RR = 0.52; 95% CI, 0.25-1.09 for Roux-En-Y bypass). Egger's test showed no indication of publication bias (p = 0.417). CONCLUSIONS: MBS is associated with reduced PCa risk regardless of T2D, with a more pronounced effect in T2D patients. Additional research is needed to investigate the impact of MBS types on PCa.

Unveiling shared diagnostic biomarkers and molecular mechanisms between T2DM and sepsis: Insights from bioinformatics to experimental assays.

Septic patients with T2DM were prone to prolonged recovery and unfavorable prognoses. Thus, this study aimed to pinpoint potential genes related to sepsis with T2DM and develop a predictive model for the disease. The candidate genes were screened using protein-protein interaction networks (PPI) and machine learning algorithms. The nomogram and receiver operating characteristic curve were developed to assess the diagnostic efficiency of the biomarkers. The relationship between sepsis and immune cells was analyzed using the CIBERSORT algorithm. The biomarkers were validated by qPCR and western blotting in basic experiments, and differences in organ damage in mice were studied. Three genes (MMP8, CD177, and S100A12) were identified using PPI and machine learning algorithms, demonstrating strong predictive capabilities. These biomarkers presented significant differences in gene expression patterns between diseased and healthy conditions. Additionally, the expression levels of biomarkers in mouse models and blood samples were consistent with the findings of the bioinformatics analysis. The study elucidated the common molecular mechanisms associated with the pathogenesis of T2DM and sepsis and developed a gene signature-based prediction model for sepsis. These findings provide new targets for the diagnosis and intervention of sepsis complicated with T2DM.

Periodontitis and Diabetes Differentially Affect Inflammation in Obesity.

Periodontitis (PD) potentiates systemic inflammatory diseases and fuels a feed-forward loop of pathogenic inflammation in obesity and type 2 diabetes (T2D). Published work in this area often conflates obesity with obesity-associated T2D; thus, it remains unclear whether PD similarly affects the inflammatory profiles of these 2 distinct systemic diseases. We collected peripheral blood mononuclear cells (PBMCs) from cross-sectionally recruited subjects to estimate the ability of PD to affect cytokine production in human obesity and/or T2D. We analyzed 2 major sources of systemic inflammation: T cells and myeloid cells. Bioplex quantitated cytokines secreted by PBMCs stimulated with T cell- or myeloid-targeting activators, and we combinatorially analyzed outcomes using partial least squares discriminant analysis. Our data show that PD significantly shifts peripheral T cell- and myeloid-generated inflammation in obesity. PD also changed myeloid- but not T cell-generated inflammation in T2D. T2D changed inflammation in samples from subjects with PD, and PD changed inflammation in samples from subjects with T2D, consistent with the bidirectional relationship of inflammation between these 2 conditions. PBMCs from T2D subjects with stage IV PD produced lower amounts of T cell and myeloid cytokines compared with PBMCs from T2D subjects with stage II to III PD. We conclude that PD and T2D affect systemic inflammation through overlapping but nonidentical mechanisms in obesity, indicating that characterizing both oral and metabolic status (beyond obesity) is critical for identifying mechanisms linking PD to systemic diseases such as obesity and T2D. The finding that stage IV PD cells generate fewer cytokines in T2D provides an explanation for the paradoxical findings that the immune system can appear activated or suppressed in PD, given that many studies do not report PD stage. Finally, our data indicate that a focus on multiple cellular sources of cytokines will be imperative to clinically address the systemic effects of PD in people with obesity.

Albuminuria-based stratification of end-stage kidney disease progression and mortality with sodium-glucose cotransporter 2 inhibitors (SGLT2i): A retrospective cohort study in type 2 diabetes and chronic kidney disease.

BACKGROUND: Clinical trials have shown the kidney-protective benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i). However, their real-world impact, particularly across varying levels of albuminuria, remains less well understood. This study aimed to evaluate the association of SGLT2i, compared with other oral glucose-lowering drugs, with end-stage kidney disease (ESKD) progression in patients with type 2 diabetes and chronic kidney disease (CKD) stratified by urine albumin-to-creatinine ratio (UACR) levels. METHODS: Using data from a national database spanning from 2016 to 2021, the study included patients with type 2 diabetes and CKD with estimated glomerular filtration rates (eGFRs) below 60 mL/min/1.73 m2 and who started on SGLT2i or other oral glucose-lowering drugs. Patients were stratified into groups by UACR ≥300 mg/g and <300 mg/g. Propensity score matching was used to minimize confounding, and progression to ESKD was evaluated using competing risks and Cox proportional-hazards models. All-cause mortality was also analyzed. RESULTS: Following propensity score matching, 18,514 patients in the severely increased albuminuria group (UACR ≥300 mg/g) were tracked, with 2.6% progressing to ESKD over 3 years. In contrast, only 0.3% of the 26,946 patients with UACR <300 mg/g progressed to ESKD. SGLT2i use was associated with a 30% reduction in risk of ESKD progression, compared with the use of other oral glucose-lowering drugs, in the severely increased albuminuria group (hazard ratio[HR]: 0.70, 95% confidence interval [CI]: 0.61-0.80). In the lower albuminuria group, no significant association was evident, though there was a nonsignificant trend toward protection over time. A consistent reduction in mortality risk was observed across all albuminuria levels. CONCLUSIONS: SGLT2i are associated with a reduction in the progression to ESKD among patients with severely increased albuminuria, with less pronounced effects observed in those with lower albuminuria levels, suggesting variability in renal outcomes based on albuminuria severity. The consistent survival benefit across all albuminuria levels supports the potential utility of SGLT2i in diabetes and CKD treatment strategies, emphasizing the need for more targeted research.

Perirenal fat and chronic kidney disease in type 2 diabetes: the mediation role of afferent arteriolar resistance.

AIM: Perirenal fat (PRF) is an independent predictor for chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) patients. Previous studies speculated that PRF may promote renal dysfunction through affecting renal hemodynamics. To verify this hypothesis, we studied the relationship between PRF and renal hemodynamics in T2DM. METHODS: 91 T2DM patients were included. PRF thickness (PRFT) was measured by magnetic resonance imaging. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by renal dynamic imaging. Renal vascular resistance (RVR), glomerular hydrostatic pressure (PGLO), afferent (RA) and efferent (RE) arteriolar resistance were calculated by Gomez equations. Multiple linear regression was used to determine the relationship between PRFT and renal hemodynamics. Mediation analysis was conducted to estimate the mediation effects of renal hemodynamics on the relationship between PRF and CKD. RESULTS: All patients were divided into three groups according to the tertiles of PRFT. Compared with patients in tertile 1, GFR and ERPF were significantly decreased in patients in tertile 3, while RVR and RA were significantly increased. PRFT was negatively correlated with GFR, ERPF and PGLO, and positively correlated with RVR and RA after adjustment for sex, age, visceral adipose tissue and treatments with ACE inhibitors/angiotensin receptor blockers and sodium-glucose cotransporter protein-2 inhibitors. Moreover, RVR and RA mediated the effect of PRF on GFR, with a mediated proportion of 29.1% and 41.4% respectively. CONCLUSION: In T2DM patients, PRF was negatively correlated with GFR, and positively correlated with RA. RA mediated the relationship between PRF and CKD.

Degree of Food Processing is Associated with Glycemic Control in African American Adults with Type 2 Diabetes: Findings from the TX STRIDE Clinical Trial.

BACKGROUND: Type 2 diabetes mellitus (T2DM) disproportionately affects African American (AA) populations. Despite the importance of diet in diabetes management, the association of diet quality and/or the degree of food processing with glycemic control in AA adults with T2DM remains unclear. OBJECTIVE: This study aimed to examine associations between diet quality scores and the degree of processing in the diet with HbA1c in AA adults with T2DM. DESIGN: This cross-sectional study used baseline data from participants in TX STRIDE (Texas Strength Through Resilience in Diabetes Education), an ongoing clinical trial. PARTICIPANTS/SETTING: Participants involved in this analysis (n=273) were AA adults with T2DM recruited through local churches in Austin, TX, and the surrounding areas from August 2020 through April 2023. MAIN OUTCOME MEASURES: Participants provided two 24-hour dietary recalls (one weekend and one weekday) and a blood sample to measure HbA1c. Healthy Eating Index-2015, Alternate Healthy Eating Index-2010, and Alternate Mediterranean Diet scores were calculated. The NOVA method was used to calculate the percentage of grams and calories that came from ultra-processed foods (UPF) and unprocessed or minimally processed foods (U/MPF). STATISTICAL ANALYSES PERFORMED: Linear regression and ANOVA models tested associations between the diet quality scores and degree of food processing with HbA1c, adjusting for demographic covariates. Models were stratified by insulin use after finding a significant interaction with UPF and U/MPF. RESULTS: Regression analyses revealed that the percentage of grams in the total diet from UPF was positively associated with HbA1c (ßadj =0.015, Padj =0.032) while U/MPF was inversely associated with HbA1c (ßadj = -0.014, Padj =0.043). There was no significant association between any diet quality score and HbA1c. CONCLUSIONS: In AA adults with T2DM, only the degree of food processing was associated with HbA1c. Future research should explore whether a causal relationship exists between food processing and HbA1c and investigate mechanisms by which UPFs may affect glycemic control.