Diabetes retinopathy (DR) is the main blinding complication of type 2 diabetes (T2DM). Glycated hemoglobin (HbA1c) can reflect long-term blood glucose control and optical coherence tomography (OCT) can evaluate retinal microvessels. The effects of metformin and insulin regimens on microvascular structure are not yet clear.

To explore the relationship between HbA1c levels and retinal microvascular changes in T2DM patients receiving metformin and/or insulin and to evaluate the impact of different hypoglycemic regimens on DR progression.

This retrospective study included T2DM patients with non‑proliferative DR treated between January 2023 and December 2024. After propensity score matching (PSM), 31 patients per group received metformin monotherapy (M), insulin‑based therapy (Ins), or combined therapy (M‑Ins). HbA1c, HbA1c variability (HbA1c‑SD), DR grade, central macular thickness (CMT), retinal nerve fiber layer (RNFL) thickness and superficial/deep capillary plexus (SCP/DCP) density were recorded at baseline, 1‑ and 2‑year follow‑up. Multiple linear regression and Cox regression were used.

After 2 years, HbA1c and HbA1c‑SD decreased significantly in all groups (p<0.05), with greater reduction in the M‑Ins group. DR progression was documented in 23 patients (24.7%), with rates of 16.1%, 38.7% and 19.4% in the M, Ins and M-Ins groups, respectively (p>0.05). OCT showed reduced CMT/RNFL and increased SCP/DCP density in all groups (p<0.05), with better improvement in M‑Ins group (p<0.05). HbA1c correlated positively with CMT/RNFL and negatively with SCP/DCP (p<0.05). Cox regression indicated that higher HbA1c-SD was an independent risk factor for DR progression (HR = 3.216, 95% CI: 1.011-10.230, p= 0.048), while metformin use was an independent protective factor (HR=0.694, 95% CI: 0.451-0.840, p=0.001).

Metformin plus insulin was associated with greater HbA1c reduction, decreased glycemic variability and increased retinal vessel density and may thus slow DR progression. Both HbA1c-SD and SCP density were correlated with DR progression risk, supporting the combined use of glycemic variability and OCT parameters for clinical evaluation and treatment guidance.

The atherogenic index of plasma (AIP) reflects the balance between proatherogenic and antiatherogenic lipoproteins and is a novel marker of atherosclerosis.

This study is aimed at investigating the association between AIP and microalbuminuria in T2DM.

This retrospective cross-sectional study included 254 patients with Type 2 diabetes mellitus divided into normoalbuminuria group and microalbuminuria group. Models were constructed for regression analysis. Restricted cubic spline was used to analyze the dose-response relationship between AIP and UACR. ROC curve was used to evaluate the discrimination power. The integrated discrimination improvement (IDI) was used to evaluate the incremental value of adding AIP to the base model.

AIP levels were significantly higher in the microalbuminuria group than in the normal albuminuria group (0.32 ± 0.41 vs. 0.19 ± 0.33, p = 0.005). After adjusting for sex, age, blood pressure, BMI, HbA1c, and eGFR, elevated AIP remained independently associated with microalbuminuria (OR = 3.291, 95% CI: 1.411-7.676, p = 0.006). A significant dose-response trend was observed across AIP quartiles (P for trend = 0.010), with the highest quartile showing a 3.34-fold increased risk compared with the lowest (OR = 3.344, 95% CI: 1.397-8.006, p = 0.007). HbA1c (OR = 1.330) and eGFR (OR = 0.970) were also independent risk factors. The discriminative performance of AIP alone was modest, and its incremental value over conventional risk factors was limited.

AIP is independently associated with microalbuminuria in T2DM with a significant dose-response relationship, suggesting its potential as an adjunctive risk marker for early DKD in primary care. However, its modest discriminative ability precludes use as a standalone screening tool. These hypothesis-generating findings require prospective validation.

To characterise glycaemic outcomes 4-6 years postpartum according to gestational diabetes mellitus (GDM) diagnostic thresholds and evaluate whether continuous glucose monitoring (CGM) identifies differences not captured by conventional clinical measures.

Women recruited before and after introduction of WHO GDM criteria were followed at 4 and 6 years postpartum. At each follow-up, participants underwent oral glucose tolerance testing (OGTT), HbA1c measurement, body composition assessment and 14-day CGM. Based on pregnancy OGTT results and the diagnostic criteria in use at the time of testing, women were classified as meeting EASD 1991 criteria (GDM_OLD; higher glucose thresholds), meeting WHO 2013 criteria but not EASD 1991 without diagnosis and treatment (GDM_WHO-) or meeting WHO 2013 criteria with diagnosis and treatment (GDM_WHO+).

Women classified as GDM_OLD had higher fasting glucose at both follow-ups compared with women meeting only WHO 2013 criteria, and showed greater hyperglycaemic exposure and glycaemic variability on CGM. Time above range, coefficient of variation and mean amplitude of glycaemic excursions were consistently higher in GDM_OLD group, and differences remained significant after adjustment for pregnancy glucose levels. Within the WHO-defined groups, conventional clinical measures did not differ between women with and without a GDM diagnosis, whereas CGM detected modest differences in mean glucose and time above range over time. Approximately 50% of women meeting only WHO 2013 criteria had prediabetes. CGM metrics were strongly associated with OGTT-derived glucose and HbA1c but only weakly with anthropometric and blood lipid measures. BMI and body fat percentage did not differ between groups.

Long-term glycaemic risk aligns with diagnostic thresholds used during pregnancy. Women diagnosed by older, higher thresholds exhibit a persistently less favourable glycaemic profile. Women meeting the lower WHO 2013 glucose thresholds represent a large group with a high prevalence of prediabetes, regardless of diagnosis during pregnancy. CGM detects modest differences in free-living glycaemic patterns not apparent from conventional clinical measures.

This network meta-analysis addresses the limited dose-specific comparative evidence by evaluating different doses of tirzepatide (TZP) versus dulaglutide (DULA) for glycemic control, weight loss, and safety in type 2 diabetes mellitus (T2DM).

Following PRISMA and Cochrane guidance, we searched major databases for RCTs comparing TZP and DULA in adults with T2DM. Efficacy outcomes included body weight change (Weeks 12 and 16) and mean HbA1c change (Weeks 12 and 24). Safety outcomes included mortality, cardiovascular events, and adverse events (AEs). SUCRA ranking was used and analysis performed in RStudio (v4.5.1).

Four RCTs comprising 14,348 participants contributed to a seven-node network. However, Nicholls et al. 2025 had the majority of sample size (n = 13,165). TZP 15 mg achieved the greatest reduction in body weight at Week 16 (mean difference [MD] vs. TZP 5 mg: -2.68 kg; 95% CI -4.98 to -0.38), while TZP 1 mg (MD: 4.39 kg; 95% CI 1.28 to 7.51) and DULA 0.75 mg (MD: 3.10 kg; 95% CI 0.25 to 5.96) were associated with smaller reductions relative to TZP 5 mg. TZP 15 mg also produced the largest HbA1c reduction at Week 24 (MD vs. TZP 5 mg: -0.40%; 95% CI -0.62 to -0.19), compared with TZP 10 mg (MD: -0.23%; 95% CI -0.44 to -0.02) and DULA 1.5 mg (MD: 0.67%; 95% CI 0.25 to 1.09). No significant differences were observed between treatments for all-cause mortality or major cardiovascular events. Gastrointestinal AEs were more frequent with higher TZP doses, especially TZP 15 mg vs. TZP 5 mg for nausea, while serious AEs and severe hypoglycemia were similar across doses.

Higher TZP doses potentially improve efficacy, while lower TZP/DULA doses enhance tolerability, supporting individualized T2DM care. However, these findings should be interpreted cautiously because several comparisons are indirect, many participants had not reached their maintenance dose, several safety outcomes were based on limited event counts, and significant inconsistency was observed for early body-weight outcomes.

This study aims to develop a machine-learning-based risk prediction model for a long-term visual prognosis in patients with proliferative diabetic retinopathy (PDR) following pars plana vitrectomy (PPV).

We analysed 609 PDR patients (609 eyes) who underwent PPV at Shanxi Eye Hospital from January 1, 2022, to January 1, 2025. The dataset was randomly split into training and validation sets at an 8:2 ratio. Candidate risk factors were identified using LASSO regression, followed by multivariate logistic regression to determine independent predictors. Machine learning algorithms were then trained to construct the prediction model, with performance evaluated by AUC-ROC, accuracy, precision, recall, and F1 score. Calibration was assessed via calibration curves, and clinical utility by decision curve analysis (DCA).

LASSO regression and multivariate logistic regression indicated that several factors influenced postoperative long-term visual prognosis. These included Renal Insufficiency (OR = 6.932, 95% CI: 3.394-14.158), Preoperative iris neovascularization (OR = 7.674, 95% CI: 3.699-15.920), Silicone oil tamponade (OR = 2.799, 95% CI: 1.641-4.707), Indirect bilirubin (IBIL) (OR = 0.902, 95% CI: 0.829-0.981) (p < 0.05). LightGBM was found to be the best for predicting postoperative long-term visual prognosis risk in PDR patients. The LightGBM model demonstrated good calibration in both training and validation sets. DCA of the validation set showed clinical net benefit at low-to-moderate risk thresholds, outperforming both 'treat-all' and 'treat-none' strategies.

In conclusion, this study developed a machine learning-based prognostic model for long-term visual prognosis in PDR patients after PPV, visualized as a proof-of-concept web calculator to assist clinical staff in early risk identification and support personalised treatment planning, pending external validation and prospective evaluation.

Early detection of diabetic macular edema (DME) is essential to prevent vision loss through timely treatment. Optical coherence tomography (OCT) is the diagnostic gold standard but is not suitable for home monitoring. The Amsler grid represents a simple and inexpensive potential screening tool. This study aimed to determine the sensitivity of the Amsler grid for detecting DME and to assess its association with the size of foveal edema.

In this cross-sectional study, 1,444 eyes of 722 diabetic patients were examined using Spectralis OCT and the Amsler grid, and 90 eyes with DME were identified. A sensitivity analysis restricted to one eye per participant and excluding eyes with concomitant macular pathologies included 34 eyes with intrafoveal DME, in which the area of foveal edema was quantified.

For very small DME (area ≤ 0.01 mm²), the sensitivity of the Amsler grid was 20.0% (1/5 eyes). For edema areas > 0.01 mm², the sensitivity increased to 62.1% (18/29 eyes), and for areas > 0.03 mm², it increased to 69.6% (16/23 eyes).

The Amsler grid demonstrated limited sensitivity for detecting DME, particularly for small edema areas (≤ 0.01 mm²). While it may serve as an adjunctive tool for home monitoring in diabetic patients, it cannot replace OCT-based examinations at recommended follow-up intervals.

Fournier's gangrene (FG) is a rapidly progressive, life-threatening necrotising soft tissue infection of the perineum and external genitalia that remains a surgical emergency with a high mortality despite advances in critical care. Once considered idiopathic, contemporary evidence demonstrates that FG most often arises from identifiable anorectal, urogenital, or cutaneous sources in patients with significant comorbidities, particularly diabetes mellitus and other states of immunocompromise. Mortality remains substantial, typically in the range of 20-30% and is strongly influenced by delays in diagnosis and definitive surgical intervention. This review updates and expands the previous 1998 review (Smith et al.) synthesising recent literature on the epidemiology, pathophysiology, microbiology, clinical presentation, diagnostic principles, management strategies, and outcomes of FG. Emphasis is placed on FG as a primarily clinical diagnosis requiring a high index of suspicion in patients presenting with rapidly progressive perineal pain and infection disproportionate to the physical findings. Prompt and aggressive surgical debridement remains the cornerstone of management, supported by broad-spectrum antimicrobial therapy, intensive supportive care, and a multidisciplinary approach, while the role of adjunctive therapies such as hyperbaric oxygen therapy and negative pressure wound therapy is critically appraised. Despite improvements in recognition and treatment, FG continues to carry significant morbidity and mortality, underscoring the importance of early diagnosis, immediate pathogen control, and coordinated multidisciplinary care to optimise patient outcomes.

Prediabetes is a critical window for preventing progression to type 2 diabetes mellitus (T2DM). Both vitamin D deficiency and physical inactivity are associated with impaired glucose metabolism. This study compared the effects of Traditional Chinese Exercise (TCE) and Kuanle Equipment Exercise (KEE) on glycaemic measures, lipid profiles, body composition and serum 25-hydroxyvitamin D₃ [25(OH)D₃] in middle-aged and elderly adults with prediabetes.

We conducted a 12-week, single-centre, randomised controlled trial involving 62 participants with prediabetes (mean age 55.2 ± 8.4 years; 88.7% female). Participants were randomly assigned to control (usual care, n = 21), TCE (n = 20), or KEE (n = 21). Primary outcomes included fasting plasma glucose (FPG), 2-h OGTT glucose, glycated haemoglobin (HbA1c) and serum 25(OH)D₃. Secondary outcomes comprised triglycerides, total cholesterol, LDL-C, HDL-C and body composition.

At baseline, mean serum 25(OH)D₃ was 21.53 ± 3.90 nmol/L. At 12 weeks, both TCE and KEE improved FPG, 2-h OGTT glucose, HbA1c and 25(OH)D₃ versus control (all p ≤ 0.001). Relative changes in FPG were -9.4% (TCE) and -15.2% (KEE) versus -1.5% (control); corresponding changes were -14.6% and -21.2% for 2-h OGTT glucose, -6.7% and -12.9% for HbA1c, and +60.6% and +81.9% for 25(OH)D₃. Direct TCE-KEE comparisons were not significant (all p > 0.05). In an exploratory analysis, change in 25(OH)D₃ was inversely associated with change in 2-h OGTT glucose (partial r = -0.358, p = 0.006), but not with FPG, HbA1c, or triglycerides.

Both TCE and KEE improved glycaemic outcomes and increased serum 25(OH)D₃ compared with usual care in middle-aged and elderly adults with prediabetes. Although KEE produced numerically larger estimates, direct between-group comparisons were not significant, and the superiority of KEE over TCE was not established. These vitamin D findings require confirmation in trials that quantify sunlight exposure and dietary vitamin D intake.

Melioidosis is an infectious disease caused by the Gram-negative bacterium Burkholderia pseudomallei. The disease is difficult to diagnose and treat. Here, we investigated outcomes of patients with suspected or confirmed melioidosis in Laos and Thailand.

We conducted a prospective, multinational, multicenter, observational study at Mahosot Hospital (MH) in Laos, and Srinagarind Hospital (SRH) and Sunpasitthiprasong Hospital (SUH) in Thailand. We enrolled adult patients (age ≥ 18 years) with suspected or confirmed melioidosis. For suspected-melioidosis cases, patients who had septic shock, had sepsis with at least one risk factor associated with melioidosis (including diabetes mellitus, chronic kidney disease, thalassemia major, malignancy and immunosuppressive therapy) or were prescribed ceftazidime or meropenem by attending physicians were enrolled, provided they were within 24 hours of hospitalization at the study hospitals. For confirmed-melioidosis cases, patients who had a clinical specimen tested positive for B. pseudomallei by either culture or antigen-detecting immunofluorescence microscopy were enrolled. The primary endpoints were 28-day and 90-day mortality.

From November 2023 to October 2024, 627 patients were screened and 200 patients were enrolled (43 for suspected-melioidosis and 157 for confirmed-melioidosis). Five of 43 patients enrolled with suspected-melioidosis (12%) were subsequently diagnosed with culture-confirmed melioidosis since enrollment. 28-day and 90-day mortality were 14% (6/43) and 23% (10/43) in suspected-melioidosis patients, respectively; and 25% (39/157) and 36% (57/157) in confirmed-melioidosis patients, respectively. In multivariable Cox regression models, higher Sequential Organ Failure Assessment (SOFA) score at enrollment and intensive care unit (ICU) admission on the day of enrollment were strongly associated with mortality outcomes. Admission to SRH and longer duration of symptoms prior to enrollment were independently associated with survival outcomes.

Future clinical trials aiming to reduce mortality in patients with suspected or confirmed melioidosis should consider stratification based on the severity of organ dysfunction at enrollment. Differences in mortality between study sites may reflect residual confounding and should be carefully considered in sample size calculations.

BackgroundThe management of type 2 diabetes mellitus (T2DM) using peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists is currently limited by the adverse effects of thiazolidinediones (TZDs), such as fluid retention and weight gain. This necessitates the search for safer natural alternatives.MethodsThis study applied an integrated multi-layer in silico pipeline to screen 19 isoflavonoids from the FooDB database against the PPAR-γ crystal structure (PDB: 3DZY). The workflow combined molecular docking (Glide SP), structural interaction fingerprint (SIFt) validation and density functional theory (DFT) for electronic characterization followed by ADMET profiling and prediction of PASS bioactivity. Molecular dynamics (MD) simulations (100 ns) and MM-GBSA binding free energy calculations were performed to explore dynamic stability and thermodynamic affinity of the complex.ResultsGenistin (FDB012221) and daidzin (FDB012225) were identified as lead candidates with docking score of -10.837 and -10.125 kcal/mol respectively. DFT analysis revealed that FDB012221has better kinetic stability with a large HOMO-LUMO gap of 7.80 eV, in addition, it was identified as drug-like by ADMET profiling, showing 58% human intestinal absorption and PASS analysis predicted. Molecular dynamics (MD) simulations validated the stable complex formation and FDB012221retained consistent hydrogen bonds with HIS435 (91%) and LEU325 (94%)further, the MM-GBSA values were -60 kcal/mol indicating strong thermodynamic binding.ConclusionFDB012221 is a potent PPAR-γ agonist with high binding affinity, electronic stability and a favorable pharmacokinetic profile. This isoflavonoid is a potential natural scaffold for the development of safer therapies for T2DM and is recommended for further in-vitro and in-vivo validation.