Diabetic chronic wounds present formidable clinical challenges due to a vicious cycle of methicillin-resistant Staphylococcus aureus (MRSA) infections, persistent hypoxia, and chronic inflammation. We herein report a sprayable and rapidly photo-cross-linkable hydrogel (LMG@GH-MA) that integrates a specially engineered microwave (MW)-responsive luteolin-based nanozyme (Lut-Mn/MnO2) with glucose oxidase (GOx). The rational design features a notable Mn4+/Mn3+ mixed-valence state in the nanozyme, which not only exhibits superior multienzyme-like activities but also serves as a robust MW susceptor, converting electromagnetic energy into localized mild hyperthermia (40.4 °C). This thermal activation enables self-amplifying catalytic cascade, where heat-enhanced GOx consumes wound glucose to produce H2O2, which is then efficiently converted into therapeutic oxygen by the heat-augmented Lut-Mn/MnO2, thereby synchronously alleviating hyperglycemia and hypoxia. Furthermore, the system achieves potent antibiotic-free antibacterial efficacy (99.19% ± 0.14%) against MRSA through a combined assault of physical membrane disruption and profound metabolic interference. The MRSA-infected diabetic rat model confirms superior therapeutic outcomes, including near-complete wound closure by Day 12, effective MRSA clearance, and reduced inflammation. Crucially, we provide strong functional evidence that LMG@GH-MA actively remodels the immune microenvironment by suppressing key pro-inflammatory pathways (e.g., IL-17, TNF-α), thereby shifting the wound milieu from a chronic inflammatory state to a pro-regenerative one. Our work integrates an approach that merges advanced nanotechnology with accessible physical stimuli, offering a promising strategy that warrants further investigation for intractable diabetic wound regeneration.

To determine the expression and clinical association of Wnt3a in T2DM, and to explore its correlation with β-cell functional parameters. Bioinformatics analysis was performed using the GSE25724 dataset. A case-control study (n = 1026) was conducted to measure serum Wnt3a and genotype Wnt3a rs12401893. High-fat diet (HFD)-induced mice, Wnt3a knockout mice, and AAV-mediated Wnt3a overexpression were used for in vivo experiments. Insulin-resistant MIN6 cells with Wnt3a knockdown or recombinant Wnt3a treatment were used for in vitro assays. Wnt3a was significantly downregulated in pancreatic tissues of T2DM patients. Serum Wnt3a was lower in T2DM patients (AUC = 0.733) and correlated with metabolic parameters. The GG genotype of rs12401893 was associated with higher T2DM risk, while AA+GA was protective. In HFD mice, serum and pancreatic Wnt3a were decreased, accompanied by insulin resistance and islet damage. In vitro, Wnt3a knockdown impaired β-cell function, whereas recombinant Wnt3a improved it. In vivo, Wnt3a deficiency aggravated HFD-induced metabolic disorders, and Wnt3a overexpression alleviated hyperglycemia and preserved islet function. Wnt3a levels are correlated with β-cell functional markers and glucose tolerance in vitro and in vivo. Wnt3a may serve as a potential adjunctive biomarker for T2DM, and its candidacy as a therapeutic target warrants further investigation.

Diabetic striatopathy is a reversible cause of acute chorea occurring in patients with poorly controlled diabetes mellitus, including those even with complex comorbidities like HIV. Timely neuroimaging and prompt metabolic correction are crucial, emphasizing the need for high clinical suspicion.

There is a history of using the medicinal plant Chaetocarpus genus, native to Southeast Asia, to treat a wide range of illnesses. The absence of detailed pharmacological validation for this plant is unexpected, considering its importance in ethnopharmacology. This study was supposed to conduct a laboratory evaluation of the pharmacological properties of the methanol extract of Chaetocarpus castanocarpus bark (MECCB). The MECCB was prepared by cold maceration and then subjected to phytochemical measurement (total phenolic, flavonoid, and tannin content) and antioxidant testing ([2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging]). Oral glucose tolerance tests were utilized to evaluate hypoglycemic potential, yeast-induced pyrexia to measure antipyretic effects, castor oil-induced diarrhea to measure antidiarrheal activity, and acetic acid-induced writhing and formalin tests to evaluate analgesic effects in vivo. The study used standard treatments, 200 and 400 mg/kg MECCB in contrast to the control group in Swiss albino mice. At 400 mg/kg, MECCB exhibited a writhing inhibition of 73.86%, demonstrating dose-dependent antinociceptive effectiveness. MECCB-treated groups showed a significant reduction in fever compared to the vehicle control group. A decrease of 37.06% in intestinal motility and a reduction of 58.53% in diarrheal feces were among the antidiarrheal effects. The fast drop in glucose levels (Δ = 6.5 mmol/L) caused by hypoglycemia was comparable to the effects of glibenclamide. The IC50 of MECCB in the DPPH assay is 418.73 μg/mL, demonstrating its antioxidant activity. This activity is associated with the high amounts of flavonoids (280.143 ± 45.122 mg QE/g) and phenolics (364.917 ± 27.0159 mg GAE/g) present. MECCB's potential as a natural medication is supported by its positive effects on pain relief, fever reduction, diarrhea treatment, and glucose regulation. Additional research is needed to identify active compounds and elucidate their mechanisms.

Post-pancreatitis diabetes mellitus after acute pancreatitis (PPDM-A) is increasingly recognized as a distinct metabolic complication rather than a simple subtype of type 2 diabetes. This narrative review summarizes current evidence on PPDM-A, with emphasis on terminology, diagnostic timing, epidemiology, pathophysiology, risk factors, clinical phenotypes, screening, prevention, and long-term follow-up. A structured literature search was conducted in PubMed/MEDLINE, Scopus, and Google Scholar to identify relevant studies. PPDM-A may develop after mild, moderately severe, or severe acute pancreatitis, although the risk is greatest in patients with pancreatic necrosis, recurrent attacks, exocrine pancreatic dysfunction, obesity, dyslipidemia, fatty liver disease, metabolic comorbidities, and marked in-hospital glycemic variability. A major diagnostic challenge is distinguishing transient stress hyperglycemia and previously unrecognized diabetes from incident PPDM-A. Formal diagnosis should generally be established no earlier than 90 days after the index episode of acute pancreatitis to minimize misclassification due to transient stress-related dysglycemia. Follow-up assessment should combine fasting plasma glucose and HbA1c, whereas a 75-g oral glucose tolerance test (OGTT) may provide greater sensitivity during early recovery, particularly when HbA1c is unreliable, results are borderline or discordant, or isolated postprandial dysglycemia is suspected. Current evidence indicates that PPDM-A develops through interacting pathogenic domains, including pancreatic endocrine injury with impaired β-cell reserve, metabolic dysregulation characterized by insulin resistance and persistent inflammation, exocrine pancreatic dysfunction with nutritional consequences, and emerging mechanisms involving gut microbiome alterations, bile acid-FGF19 signaling, and extracellular vesicle-mediated communication. Available data support a trajectory-based model in which some patients recover normal glucose metabolism, some develop persistent intermediate dysglycemia, and others progress to overt diabetes over months or years. Structured post-discharge surveillance, risk-stratified follow-up, assessment of exocrine dysfunction, and prevention of recurrent pancreatic injury are essential for improving early detection, reducing diagnostic misclassification, and optimizing long-term clinical outcomes.

Diabetic autonomic neuropathy is a clinically important component of diabetic neuropathy involving the cardiovascular, gastrointestinal, genitourinary, sudomotor, pupillary, and glucose counterregulatory systems. Cardiovascular autonomic neuropathy (CAN) has been extensively studied and is clinically relevant because of its association with adverse cardiovascular and renal outcomes. Early CAN is frequently silent and may only be recognized by reduced heart rate variability or abnormal cardiovascular autonomic reflex testing. As CAN progresses, patients develop resting tachycardia, reduced exercise tolerance, orthostatic or postprandial hypotension, abnormal nocturnal blood pressure regulation, and perioperative hemodynamic instability. Non-cardiovascular manifestations include gastroparesis, bowel and bladder dysfunction, erectile dysfunction, sudomotor and pupillary abnormalities, and impaired hypoglycemic awareness. The underlying mechanisms involve chronic hyperglycemia, glycemic variability, dyslipidemia, insulin resistance, oxidative and mitochondrial stress, inflammation, microvascular injury, and impaired axon-glial support. Clinically, evaluation should begin with a systematic symptom review, neurological examination, supine and standing blood pressure measurements, and heart rate assessment, followed by organ-specific testing if indicated. Treatment was based on comprehensive risk factor control and symptom-directed management.

Diabetic retinopathy is a leading cause of vision impairment and blindness in individuals with diabetes. Under conditions of chronic hyperglycemia and retinal hypoxia, pathological angiogenesis develops, increasing the risk of retinal hemorrhage. Disease progression is driven by oxidative stress and chronic inflammation, which activate complex signaling cascades that promote neovascularization. Diabetic macular edema, caused by leakage from damaged retinal vessels, is the primary cause of vision loss in diabetic retinopathy. Based on the presence of retinal neovascularization, diabetic retinopathy is classified as nonproliferative or proliferative diabetic retinopathy. Current therapies, including laser photocoagulation, intravitreal anti-vascular endothelial growth factor injections, and vitreoretinal surgery, can only partially preserve vision, underscoring the importance of early intervention to control abnormal angiogenesis. Exosomes are lipid bilayer vesicles 30-150 nm in diameter that carry bioactive molecules such as proteins, mRNAs, miRNAs, and other noncoding RNAs. They are released by many cell types, including immune cells and retinal pigment epithelium, a major source of vascular endothelial growth factor in retinopathy. This review summarizes human studies investigating the therapeutic potential of exosomes in diabetic retinopathy, with a focus on miRNAs involved in angiogenesis and their utility as biomarkers and treatment targets. Altered expression of exosomal miRNAs, including downregulated miR-204-5p in vitreous humor and upregulated miR-15a in tears and vitreous humor, may serve as diagnostic biomarkers. Exosomes derived from bone marrow mesenchymal stem cells and ARPE19 cells suppress endothelial cell proliferation, migration, and tube formation. Modulation of specific miRNAs further reduces angiogenesis. Collectively, these findings suggest that miRNA-modulated exosomes represent a promising cell-free therapeutic strategy for proliferative diabetic retinopathy, although challenges related to exosome yield and purification remain.

Although diabetic complications are well-established in multiple organs, their impact on the respiratory system remains unclear. Clinical evidence indicates accelerated chronic obstructive pulmonary disease (COPD) progression in individuals with diabetes, yet the underlying mechanisms are poorly defined. Using single-cell RNA sequencing of airway epithelium, we identified distinct transcriptional alterations in COPD patients with or without diabetes, particularly in host-defense pathways related to viral infection, which is a key driver of COPD exacerbations. Functionally, hyperglycemia enhanced influenza virus susceptibility in both COPD-derived epithelial cells and COPD mice with diabetes, indicating compromised airway defense. We further demonstrated that hyperglycemia promotes advanced glycation end products (AGEs) accumulation in airway epithelium, with AGEs levels correlating with infection severity. Pharmacological inhibition of AGEs formation with aminoguanidine significantly reduced viral load both in vitro and in vivo. Mechanistically, AGEs activate p38/ERK/IKK proinflammatory signaling via RAGE and MD2 receptors, leading to epithelial injury and heightened viral susceptibility. Our findings reveal a hyperglycemia-AGEs-RAGE/MD2 axis that increases viral susceptibility in COPD, highlighting AGEs targeting as a promising therapeutic strategy for COPD patients with diabetes.