Diabetes disproportionately impacts low- and middle-income populations, exacerbating existing health disparities. The role of hepatic biomarkers, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the ALT/AST ratio, in predicting diabetes onset remains insufficiently elucidated. This research assessed how these biomarkers relate to diabetes risk, as well as assessed the mediating effect of the triglyceride-glucose (TyG) index.

The secondary analysis utilized data from the Dryad public database, encompassing a cohort of 211,833 Chinese adults aged ≥ 20 years who underwent health examinations between 2010 and 2016. After applying rigorous exclusion criteria, 50,463 participants were included. Cox proportional hazards models were applied to examine how hepatic biomarkers and the TyG index influenced diabetes incidence. The mediation analysis was conducted to assess the TyG index's contribution to the hepatic biomarker-diabetes relationship.

Throughout the observational phase (mean 3.08 years), 1309 participants (2.59%) established diabetes. Increased levels of ALT, AST, and the ALT/AST ratio were all significantly related to a heightened diabetes risk, with the most significant correlation noted for the ALT/AST ratio (adjusted HR per unit increase: 1.04; 95% CI: 1.02-1.05; P < 0.001). Participants in the highest quartile of the ALT/AST ratio had nearly three times the risk of diabetes than the lowest quartile (HR: 2.94; 95% CI: 2.42-3.57; P < 0.001). Joint analysis revealed synergistic effects between elevated hepatic biomarkers and the TyG index, with the combination of high ALT/AST ratio and elevated TyG index yielding the greatest risk (HR: 5.23; 95% CI: 4.42-6.18; P < 0.001). The mediation analysis showed that the TyG index significantly mediated the associations, accounting for 40.25%, 36.45%, and 76.97% of the effects of ALT, AST, and the ALT/AST ratio, respectively, on diabetes risk.

Hepatic biomarkers, particularly the ALT/AST ratio, robustly predict diabetes risk in this large cohort, with the TyG index explaining most of this association. These insights reinforce the importance of integrating hepatic and metabolic assessment in preventive strategies to address the growing diabetes epidemic.

Tryptophan and its kynurenine pathway (KP) metabolites play key roles in modulating the immune system and vasculature, and exhibit both pro- and antioxidant properties, making them crucial for a healthy pregnancy and fetal development. Disruptions in the KP may impact both prenatal and postnatal health, however, data on fetal KP metabolite concentrations and their alterations in pregnancy-related disorders remain scarce. This study aims to investigate the association between pregnancy complications and KP metabolite concentrations in umbilical cord blood.

Pregnancies complicated by preeclampsia (n = 40), fetal growth restriction (FGR, n = 33), pregestational diabetes mellitus (DM, n = 42), gestational diabetes mellitus (GDM, n = 61), and amniotic infection syndrome (AIS, n = 47) were included, along with 410 controls matched in a 1:2 ratio using Mahalanobis nearest-neighbor matching from a prospective birth cohort study. Tryptophan, kynurenine, anthranilic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, kynurenic acid, xanthurenic acid, quinolinic acid, picolinic acid, and nicotinic acid were measured in umbilical cord blood using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differences in metabolite concentrations were analyzed using unpaired t-tests and linear regression models to control for potential confounders.

Tryptophan concentrations were decreased in cases of preeclampsia and DM. We identified elevated levels of 3-hydroxykynurenine in preeclampsia, kynurenine in GDM, and nicotinic acid in both FGR and DM. Quinolinic acid levels were also higher in preeclampsia and GDM, although this was not significant after adjusting for confounding variables. We observed no changes in KP metabolites in AIS.

This study identified distinct alterations in umbilical cord blood KP metabolite concentrations in pregnancies with preeclampsia, FGR, DM, and GDM, but not AIS. This suggests differential regulation and activation of the KP depending on the pregnancy disorder. Such changes may influence maternal and infant health and could play a role in fetal programming, with potential long-term effects on child development and health.

This study assessed whether early weight loss following tirzepatide treatment was associated with clinical characteristics and outcomes at 52 weeks in Japanese patients with type 2 diabetes (T2D).

Post hoc analyses used pooled data from the phase 3 SURPASS J-mono and J-combo studies, which examined tirzepatide 5, 10, and 15 mg as monotherapy or combination therapy in Japanese participants over 52 weeks. Subgroup analyses of clinical characteristics and metabolic outcomes at 52 weeks were conducted based on early weight loss achievement of < 5% or ≥ 5% after 8 weeks of tirzepatide (comprising 4 weeks each at 2.5 mg and 5 mg, per dose-escalation scheme). Selected safety outcomes were evaluated by weight-loss subgroups.

The analysis included 893 participants (< 5% subgroup: n = 683 [76.5%]; ≥ 5% subgroup: n = 210 [23.5%]). Multivariate regression analysis showed that participant clinical characteristics, including lower baseline weight, concomitant alpha-glucosidase inhibitor use, and lack of concomitant sulfonylurea use, were independently predictive of achieving ≥ 5% weight loss at 8 weeks. Clinically significant reductions with tirzepatide were observed in body mass parameters over 52 weeks in both subgroups, with greater weight reductions observed at week 52 in the ≥ 5% subgroup versus the < 5% subgroup (5 mg: - 13.8% vs. - 4.1%; 10 mg: - 16.5% vs. - 8.8%; 15 mg: - 20.0% vs. - 11.5% [p < 0.001, all comparisons]). Blood pressure and lipid level improvements were also significantly greater in the ≥ 5% subgroup. Improvements in glycated hemoglobin were similar between subgroups; however, the ≥ 5% subgroup had a higher proportion of participants who achieved normoglycemia at week 52 with a shorter time to reach normoglycemia. Tirzepatide was generally well tolerated across the weight-loss subgroups.

These findings suggest early weight loss following tirzepatide may be predictive of metabolic outcomes at 52 weeks in Japanese patients with T2D. These data may inform clinical management of tirzepatide-treated patients.

GOV: NCT03861052, NCT03861039.

Prediabetes progression to type 2 diabetes mellitus (T2DM) can be effectively prevented by adequate dietary intervention via improved liver insulin resistance. Stevioside, as a natural and safe sweetener, has been shown to have antidiabetic properties. However, whether stevioside can enhance liver insulin resistance in prediabetes remains unclear. We therefore aimed to investigate the effect and molecular mechanisms of stevioside on liver insulin resistance in prediabetes. Prediabetic mice were induced using a high-fat diet and treated with stevioside for 8 weeks. The effects of stevioside on gene expression levels and signaling pathways in the mice liver were investigated by RNA-seq and gene enrichment analysis. We also treated the palmitic acid-induced insulin-resistance AML-12 cells with stevioside,  and measured glucose uptake in insulin-stimulated cells with 2-NBDG. The expression levels of genes and proteins related to the insulin signaling pathway were detected using qRT-PCR and Western blotting. Stevioside improved glucose tolerance and plasma insulin levels in prediabetic mice with insulin resistance and enhanced liver function. Stevioside could improve liver insulin resistance via IRS1/PI3K/AKT signaling pathway in prediabetic mice. Similarly, stevioside decreased the level of p-IRS1 and increased the levels of p-PI3K p85α, AKT, and p-AKT in AML-12 cells. Stevioside could improve glucose tolerance in prediabetic mice with insulin resistance, and ameliorate liver insulin resistance by regulating the IRS1/PI3K/AKT signaling pathway. These results may support stevioside as a potential dietary approach for preventing prediabetes progression to T2DM.

A five-month-old female mixed-breed dog presented with a two-week history of polyuria, polydipsia, and vomiting. Clinical examination revealed poor body condition, growth retardation, pale oral mucous membranes, weak pulse, and prolonged capillary refill time. Laboratory findings included neutrophilic leukocytosis with a regenerative left shift, fasting hyperglycemia, elevated fructosamine, glycated hemoglobin, and β-hydroxybutyrate concentrations, while the acid-base balance remained normal. Canine-specific pancreatic lipase and trypsin-like immunoreactivity concentrations ruled out an underlying pancreatitis or exocrine pancreatic insufficiency, respectively. Urinalysis showed glycosuria and ketonuria. Supportive care included antibiotics and regular insulin administration. Abdominal ultrasonography identified a pancreatic cavity with a thick wall and mixed echogenic fluid. Ultrasound-guided drainage was performed without complications. Cytology confirmed a pancreatic abscess with pyogranulomatous inflammation, though the culture results were negative. The dog was discharged with intermediate-acting lente insulin. Follow-up ultrasonographic evaluations at 7, 14, and 21 days and 5 months post-drainage showed no recurrence. The diabetes remained well-controlled one year post-discharge. This case report describes the successful management of a dog with juvenile diabetes mellitus complicated by a pancreatic abscess, highlighting the effectiveness of percutaneous ultrasound-guided drainage combined with medical therapy.

(1) Background: In the absence of locally validated tools, the CHA2DS2-VA score has been suggested as a substitute for the CHA2DS2-VASc score. This study compared the potential discrepancies between these scores. (2) Methods: The observational, retrospective, and community-based study included a cohort of 3370 patients with a new diagnosis of atrial fibrillation (AF) between 1 January 2015 and 31 December 2024. (3) Results: AF prevalence was 8.4%, which was significantly higher in men. The mean age was 80.1 (SD ± 6.24) years. Women (42.8%) were older (80.9 SD ± 6.1 vs. 79.5 SD ± 6.23; p < 0.001). Men had more instances of diabetes mellitus, peripheral vascular disease, coronary artery disease, and chronic obstructive pulmonary disease, as well as a higher Charlson Comorbidity Index. Conversely, women exhibited a higher proportion ≥75 years, including cognitive impairment, dyslipidemia, and higher stroke risk, as assessed by the CHA2DS2-VASc score (p < 0.001) but not by the CHA2DS2-VA score (p = 0.071). The CHA2DS2-VA score reduced the sex-based risk stratification differences, and only 3.2% of women were reclassified as being at very low risk (CHA2DS2-VA < 2). (4) Conclusions: The CHA2DS2-VA score notably redefined sex-based thromboembolic risk stratification profiles, with no sex-based disparities in the selection of OAC treatment modality. The clinical utility of CHA2DS2-VA remains a subject of ongoing debate.

Sarcopenic obesity is closely related to metabolic dysfunction-associated steatotic liver disease (MASLD), but the independent contributions of lean mass and fat mass components to MASLD are not well understood. Our study aimed to evaluate the relationship between the dual-energy X-ray absorptiometry (DXA)-derived soft tissue components and the extent of liver steatosis in patients with MASLD.

A cross-sectional study of 118 obese/overweight patients aged 33-78 years, with type 2 diabetes mellitus (T2DM) or prediabetes and MASLD, on oral antidiabetic medication was conducted. Sex-stratified correlation analysis was performed between DXA-derived lean mass and fat mass parameters, (e.g., relative muscle mass [RMM], lean mass/ fat mass [LM/FM] and appendicular lean mass [ALM]), as well as between each of those parameters and the hepatic steatosis index (HSI). Multiple linear regression models were fitted with android fat percentage as the dependent variable, and lean mass indices as independent variables. The models were adjusted for age, sex, the HOMA index, triglyceride and ALT levels. Accordingly, ROC curves were plotted with HSI=36 as a classifier of steatosis.

A significant negative correlation was detected between android fat % and RMM (r=-0,96, P≤0.001), between android fat percentage and ALM /BMI (r=-0.70, P≤0.001), between android fat percentage and ALM /height² (r=-0.28, P≤0.001); between HSI and RMM (r=-0.50, P≤0.001); and between HSI and ALM/BMI (r=-0.39, P≤0.001). The significant positive correlations were as follows: android fat percentage and BMI (r=0.53, P≤0.001); android fat % and ALT (r=0.25, P=0.04); HSI and android fat percentage (r=0.59, P≤0.001); HSI and gynoid fat % (r=0.39, P≤0.001). The AUCs for android fat percentage in the models calculated from LM/FM were as follows: adjusted for the HOMA index, age and sex group, ROC=0.748 (95% CI 0.66-0.83); adjusted for ALT and sex group, ROC=0.743 (95% CI 0.66-0.83). The AUC for android fat percentage in the model calculated from RMM: adjusted for triglycerides, ALT and sex group, ROC=0.741 (95% CI 0.65-0.83).

Our findings demonstrate that an increase in android fat distribution and a decrease in lean mass are positively associated with MASLD. The regression models support the utility of DXA-derived indices as practical, indirect markers of liver steatosis for clinical application in patients with TDM2 and MASLD.

T cells are crucial in destroying pancreatic β cells, resulting in insulitis in type 1 diabetes (T1D). However, only 1% to 2% of infiltrating CD8⁺ T cells are specific for islet autoantigens. The mechanisms driving non-cognate T cells to the islets and their potential pathogenic roles remain unclear.

We analyzed the frequency and function of circulating gut-tropic immune cells in 99 patients with T1D and 57 healthy controls. We also analyzed single-cell RNA sequencing on pancreata from 10 T1D donors, 11 autoantibody-positive donors, and 15 non-diabetic controls. Correlation analysis was performed to elucidate the relationship between gut-tropic cells and clinical variables. In NOD mice, we examined gut-tropic T cell frequencies, cytokine profiles, and cytotoxicity at different disease stages. Additionally, we investigated the role of integrin α4β7 on gut-tropic T cells function and migration.

Gut-tropic CD8⁺ T cells are reduced in peripheral blood but elevated in pancreatic islets of patients with T1D, correlating with impaired β-cell function. Gut-tropic CD8⁺ T cells exhibited stronger cytokine production than non-gut-tropic counterparts. In NOD mice, gut-tropic cells increased in the islets and decreased in the blood during insulitis progression. Gut-tropic CD8⁺ T cells showed augmented cytokine production and cytotoxicity against islet cells. Integrin α4β7 was a key mediator of the pathogenicity of CD8⁺ T cells and upregulated by the inflammatory signals. Insulitis directly drove gut-tropic CD8⁺ T cells migrating to inflamed islets.

Gut-tropic CD8⁺ T cells bridge the intestinal immune system and the pathogenesis of T1D, offering potential biomarkers and therapeutic targets.

The safety and clinical performance of the Supraflex Cruz sirolimus-eluting stent (SES) have not been explored within a Russian population until now.

The S-FLEX Russia registry was designed to evaluate the clinical safety and performance of the Supraflex Cruz SES in a real-world, all-comers Russian population undergoing percutaneous coronary intervention (PCI).

This was a prospective, multicentre, single-arm, observational registry that included 522 patients who underwent PCI with the Supraflex Cruz SES between August 2021 and February 2022, at five hospitals in Russia. Subgroups prespecified for data analysis included patients with diabetes mellitus, bifurcation lesions, type B2/C lesions and at least one long lesion (>20 mm). The primary endpoint was target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TVMI) and clinically driven target lesion revascularisation (CD-TLR) at 12-month follow-up.

The mean age of the patient population was 64.26±9.46 years. Device and procedural success were 99.4% and 98.9%, respectively. At 12 months, TLF was observed in 16 (3.1%) patients, comprising 8 (1.5%) cardiac deaths, 6 (1.1%) TVMI, and 2 (0.4%) CD-TLR. Only 1 (0.2%) instance of definite stent thrombosis was observed at 12-month follow-up. In the high-risk subgroups, TLF at 12 months was 5.6% in patients with diabetes, 8.5% in bifurcation lesions, 2.8% in complex B2/C lesions, and 1.9% in long lesions (>20 mm).

Low rates of TLF and stent thrombosis at 12-month follow-up demonstrate the excellent safety and clinical performance of the Supraflex Cruz SES in a real-world, all-comers Russian population, including prespecified high-risk subgroups.

Gestational diabetes mellitus (GDM) represents a prevalent metabolic disorder related to pregnancy, posing significant risks to both the expecting mother and the developing fetus. Recent research indicates a potential connection between bile acids (BAs) and GDM, such as lithocholic acid (LCA), β-muricholic acid (β-MCA), and 6,7-diketolithocholic acid (6,7-diketoLCA), have been found to be significantly increased in GDM individuals, thereby with the potential to reveal their involvement in glucose metabolism and the underlying mechanisms of GDM development. Additionally, BAs have emerged as vital signaling molecules that regulate glucose and lipid metabolism by interacting with Farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5), highlighting their potential as novel therapeutic targets for GDM management. The aim of this manuscript is to comprehensively review the current understanding of the relationship between BAs and GDM, delving into their potential mechanistic roles, diagnostic significance, and possible therapeutic applications.