RFX6 maturity-onset diabetes of the young (RFX6-MODY) is a relatively new MODY subtype, with limited guidance on management, particularly in pregnancy. We report the clinical features and management of two female patients with RFX6-MODY and their progression during and post-pregnancy. These patients were diagnosed with type 2 diabetes mellitus (DM) at ages 13 and 19 years, initially managed on dietary modification alone. They were subsequently diagnosed with RFX6-MODY during pregnancy following calculation of MODY probability. Both required insulin during pregnancy and delivered healthy babies at 38 weeks. Three months post-delivery, tirzepatide was started for one of our patients and she has shown significant glycaemic improvement and weight loss. To our knowledge, this is the first reported use of tirzepatide in RFX6-MODY.

RFX6-MODY may present at a much earlier age than previously reported in the literature. Many patients with RFX6-MODY do not appear to require insulin at diagnosis. Tirzepatide may be a beneficial therapeutic option for managing patients with RFX6-MODY who have adequate β-cell function. Pregnancy management in patients with RFX6-MODY is similar to type 2 DM, although higher insulin doses may be required.

Type 1 diabetes (T1D) results from autoimmune destruction of pancreatic β-cells. Current therapies fail to address the multiple mechanisms driving disease progression. We developed an oral Salmonella-based vaccine that partially prevented and reversed autoimmune diabetes in mice. Gastrin, an intestinal hormone, has been reported to have anti-inflammatory and β-cell-protective effects. We hypothesized that combining the vaccine with a gastrin analogue (GAST-17) could enhance therapeutic efficacy.

Female non-obese diabetic (NOD) mice were treated with the oral vaccine, GAST-17, or their combination. Blood glucose levels, islet histology, immune cell infiltration, cytokine profiles, and regulatory T cell populations were assessed. Functional assays included antigen-specific stimulation, adoptive transfer, and analysis of immunoregulatory gene expression.

Combination therapy demonstrated superior efficacy in both diabetes reversal and prevention. In reversal studies, diabetes remission was achieved in 80% of mice receiving the combination therapy, compared with 63% in the vaccine-only group and 5% in the GAST-17-only group. In prevention studies, diabetes onset was prevented in 80% of mice receiving the combination therapy, compared with 70% in the vaccine-only group and 30% in the GAST-17-only group. Therapeutic effects were associated with increased antigen-specific regulatory T-cells, reduced islet-infiltrating lymphocytes, preserved insulin-positive islet area and β-cell mass, and modulation of cytokine profiles, including elevated IL-10 and TGF-β and reduced IFN-γ, GM-CSF, IL-1α, and IL-12. Upregulation of immune checkpoint molecules (CTLA-4 and PD-L1) and immunoregulatory mediators (AhR, IDO, and IL-27) was observed, suggesting a potential contribution to immune homeostasis.

The combination of the oral Salmonella-based vaccine and GAST-17 improved glycemic control in NOD mice and was strongly associated with β-cell preservation and immune regulation. This dual-acting strategy, integrating immune modulation with β-cell preservation, may offer durable therapy in autoimmune diabetes and could have potential for future clinical translation.

To report a case of advanced lung adenocarcinoma (LUAD) harboring KRAS p.G12C and TP53 p.R273C mutations. While immune checkpoint inhibitor (ICI) therapy offered remarkable clinical benefits, it concurrently induced a fatal endocrine complication, highlighting the dual-natured impact of immunotherapy.

An elderly male diagnosed with Stage IV LUAD achieved sustained stable disease (SD) and symptomatic improvement through a sequential therapeutic strategy, including platinum-based chemotherapy followed by the PD-1 inhibitor sintilimab combined with anti-angiogenic agents (apatinib or anlotinib). However, the patient developed severe coma, hyperglycemia and metabolic disorder. Laboratory investigations confirmed fulminant ICI-related diabetic ketoacidosis (DKA). Despite intensive resuscitative efforts, the patient succumbed to multi-organ failure.

This case demonstrates that while ICIs can provide exceptional long-term benefits in advanced NSCLC, particularly in patients with highly immunogenic mutation profiles, they may also trigger late-onset fatal irAEs. Our findings underscore the imperative for close, long-term metabolic surveillance throughout the course of immunotherapy, regardless of treatment duration or radiological stability.

Accurate early prognostication in acute ischemic stroke (AIS) is essential for optimizing post-thrombectomy management strategies. However, the predictive utility of baseline clinical characteristics remains underexplored in real-world emergency settings.

To identify independent clinical predictors of in-hospital neurological improvement following mechanical thrombectomy in AIS patients, with particular focus on admission NIHSS score and comorbid diabetes mellitus.

In this retrospective single-center cohort study, 250 AIS patients who underwent emergency mechanical thrombectomy between January 2020 and December 2022 were analyzed. Patients were dichotomized according to an in-hospital early neurological improvement endpoint defined a priori as ENI-4 (decrease ≥4 points in NIHSS from admission to discharge). All analyses were repeated in sensitivity analyses using two alternative definitions: a clinician-adjudicated composite of in-hospital neurological improvement and discharge NIHSS ≤1/0. Logistic regression analyses were employed to determine independent predictors. Model performance was evaluated using ROC curve analysis, calibration plots, and nomogram construction.

Among the 250 patients, 196 (78.4%) showed neurological improvement during hospitalization. Multivariate logistic regression revealed that a lower admission NIHSS score (OR = 0.867, 95% CI: 0.810-0.927; p < 0.001) and absence of diabetes mellitus (OR = 0.357, 95% CI: 0.129-0.988; p = 0.047) were independently associated with favorable short-term outcomes. The final model demonstrated moderate discriminative ability (AUC = 0.711) and good calibration. Spline analysis demonstrated a non-linear NIHSS-outcome relationship, and decision-curve analysis showed positive net benefit across 10-30% thresholds. A nomogram based on the model was developed for bedside application. Using ENI-4 as the primary outcome, lower admission NIHSS and absence of diabetes remained independently associated with in-hospital neurological improvement in the multivariable model (NIHSS OR 0.867; diabetes OR 0.357).

Lower NIHSS scores at presentation and non-diabetic status are independent predictors of early neurological improvement following thrombectomy. The internally validated model provides a clinically accessible tool for early risk stratification in AIS patients and may inform post-procedural monitoring and care planning in settings lacking long-term functional follow-up.

Current dysglycaemia detection methods have limits; glycated albumin (GA), unaffected by conditions that distort HbA1c, is proposed as an alternative. We aimed to estimate the relationship between various glycaemic parameters and their association with GA in Saudi adults to evaluate GA potential utility in screening, detecting, and monitoring diabetes (DM) and intermediate hyperglycaemia (IH).

A total of 132 biobank serum samples (-80°C) representing a wide glycaemia range, using HbA1c, fasting plasma glucose -FPG, and 1 hour plasma glucose- 1h-PG data. Serum GA was measured by ELISA and expressed as %. Correlations with glycaemic markers were assessed, group means (normoglycaemia, IH, DM) were compared, and diagnostic performance evaluated by ROC analysis. Optimal GA cut-offs for dysglycaemia and DM were determined, with significance set at P< 0.05.

Used measures of glycaemia did not consistently classify glycaemic status in the same way. The groups with IH and DM had significantly higher mean GA values compared with the normoglycaemia group (P<0.001). GA values correlated significantly with all glycaemic markers (P<0.001), showing the strongest correlation with HbA1c, and the weakest with 1h-PG. the optimal GA cut-off values for detecting dysglycaemia was 13.9% (Sensitivity= 0.786, specificity= 0.917), and 14.7% (Sensitivity= 0.857, specificity= 0.747) for DM.

GA correlated significantly with other markers and can be suggested as an alternative to detect and monitor glycaemic status among Saudis. Further research is required to determine ranges in our population.

Diabetic striatopathy (DS) is a rare neurological complication of diabetes mellitus, characterized by acute choreiform or ballistic movements and hyperintense basal ganglia lesions on T1-weighted MRI. While non-ketotic hyperglycemia is commonly implicated, DS can also occur in ketotic states.

We report two elderly patients with long-standing, poorly controlled diabetes. Case 1, an 80-year-old male, presented with bilateral lower limb choreiform movements and delirium. Case 2, a 92-year-old female, developed right-sided hemichorea after discontinuing hypoglycemic therapy. Both patients had hyperglycemia with ketosis and characteristic basal ganglia T1 hyperintensity. Intensive glycemic control and symptomatic therapy led to complete resolution of involuntary movements in both cases.

These cases highlight the heterogeneous clinical presentations of DS in advanced-aged patients and emphasize the importance of early recognition and prompt metabolic correction to achieve favorable neurological outcomes.

Type 2 diabetes mellitus (T2DM) is increasingly seen as a chronic inflammatory state, with the neutrophil-to-lymphocyte ratio (NLR) studied as a new biomarker of systemic inflammation. Evidence links NLR to glycemic control, but its consistency and strength vary. This review summarizes data on NLR's relationship with glycemic indicators, such as hemoglobin A1c (HbA1c), across different T2DM glycemic states.

A systematic literature search was carried out in PubMed/MEDLINE, Scopus, Web of Science, and Embase through November 2025 to find studies that reported both NLR and glycemic control indicators in adults with T2DM. Data were systematically extracted based on predefined criteria. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were combined using random-effects models. Heterogeneity was measured using the I² statistic, and robustness was assessed using sensitivity analyses. Publication bias was investigated using Begg's and Egger's tests, trim-and-fill analysis, and funnel plot examination. All statistical analyses were conducted using STATA 18 (StataCorp, College Station, TX, USA).

The meta-analysis consisted of 27 studies (37 comparisons) with a total of 48,714 individuals from 11 nations. NLR demonstrated a stepwise gradient with deteriorating glycemic control: poorly controlled T2DM (HbA1c >  7%) had higher NLR than well-controlled T2DM (HbA1c ≤  7%) (p <  0.001), prediabetes (HbA1c 5.7-6.4%) (p <  0.001), and normoglycemia (HbA1c ≤  5.7%) (p =  0.037).

NLR rises progressively with deteriorating glycemic control and is markedly raised in poorly controlled T2DM. These observations endorse NLR as an inexpensive, widely available inflammatory biomarker that can augment conventional glycemic measures in the clinical setting.

Severe hypoglycemia (SH) in adults with type 1 diabetes mellitus (T1DM) is associated with significant morbidity and mortality; however, its underlying causes are often complex and multifactorial. Improved tools to identify individuals at a high risk of SH are critically needed. In this study, machine learning techniques were applied to continuous glucose monitoring (CGM) data to identify distinguishing features between individuals with and without SH episodes.

We analyzed data from the real-world study of adults with T1DM enrolled in the FGM-Japan study. Eleven machine learning algorithms using continuous glucose monitoring (CGM) metrics were applied to identify SH and assess the relative importance of the contributing features. The CGM metrics included mean glucose/GMI, time above range (TAR > 250 and > 180 mg/dL), time in range (TIR 70-180 mg/dL), time below range (TBR < 70 and < 54 mg/dL), coefficient of variation (%CV), and glycemic risk index (GRI). The model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1 score.

Data from 264 adults with T1DM were analyzed. Across the models, XGBoost showed the highest AUC, significantly outperforming logistic regression, k-NN, and SVM but performed marginally below Naive Bayes. The F1-score analysis showed that logistic regression and neural networks provided a better balance between precision and recall. The model using four CGM variables (TBR < 70, %CV, GMI, and GRI) achieved the highest AUC of 0.794.

XGBoost offers strong overall discrimination; however, simpler models exhibit better F1 performance. Features like 'TBR', '%CV', 'GMI,' and 'GRI' were key features, suggesting their usefulness in identifying individuals at risk for adverse glycemic events.

Clinical Trial Registry No. UMIN000039376.

The online version contains supplementary material available at 10.1007/s13340-025-00872-4.

Obesity is a growing global epidemic, contributing to major health conditions such as cardiovascular disease (CVD), stroke, type 2 diabetes mellitus (T2DM), and cancer. The purpose of this review is to evaluate and compare obesity management strategies, with a focus on the magnitude of weight loss achieved and the adverse effects associated with each intervention. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure methodological rigor in study selection and reporting. Bariatric surgery is currently considered the most effective intervention for achieving significant and sustained weight reduction, particularly in patients with severe obesity. Procedures such as Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and adjustable gastric banding consistently demonstrate superior weight loss and metabolic improvements compared with nonsurgical therapies. However, surgery carries well-documented risks, such as gastric strictures, anastomotic leaks, thromboembolic events, infections, and the need for reoperations. Long-term challenges include nutritional deficiencies, GI complications, and, in some patients, partial weight regain. Pharmacologic options are increasingly important adjuncts or alternatives to surgery. Novel agents, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), have gained popularity due to their substantial efficacy among pharmacological options, favorable safety profile, and non-invasive nature. Other agents, including phentermine-topiramate (PHEN-TPM), naltrexone-bupropion, and orlistat, also play roles in individualized treatment plans, although weight loss outcomes are typically more modest than with surgical approaches. In conclusion, a multimodal strategy integrating surgical and medical therapy may provide the most durable results. This approach not only enhances weight loss but also supports long-term maintenance and optimizes management of obesity-related comorbidities.

Managing diabetes mellitus (DM) and its long-term complications remains a major global health challenge. Dihydromyricetin (DHM), a natural flavonoid abundant in Ampelopsis grossedentata and Hovenia dulcis, has attracted increasing attention for its multi-target anti-diabetic properties. Growing evidence indicates that DHM improves glucose metabolism, alleviates oxidative stress and inflammation, regulates autophagy and cell death, and exerts beneficial effects in DM and a range of related complications, including diabetic nephropathy, cardiomyopathy, cognitive impairment, and wound healing impairment, and other related complications. Overall, this review provides an overview of preclinical research on DHM in DM and its main complications, emphasizing its therapeutic benefits and underlying molecular mechanisms. Although DHM is promising, future research should improve its delivery, clarify its mechanisms, and carry out clinical trials to enable therapeutic use.