Diabetic gastroparesis (DGP) is a chronic and frequently underrecognized complication of diabetes mellitus, characterized by delayed gastric emptying in the absence of mechanical obstruction. It represents a clinically significant manifestation of diabetic autonomic neuropathy and arises from a complex interplay of sustained hyperglycemia, oxidative and nitrosative stress, advanced glycation end-product accumulation, impaired insulin/IGF-1 signaling, lipid dysmetabolism, and inflammatory activation. These mechanisms converge to damage autonomic and enteric neurons, reduce interstitial cells of Cajal density, and disrupt gastric smooth muscle function, ultimately leading to impaired and unpredictable gastric motility. Beyond gastrointestinal symptoms, DGP profoundly affects metabolic control. The altered timing and variability of gastric emptying disturb the physiological coordination between nutrient absorption and insulin pharmacokinetics, generating a temporal mismatch that predisposes patients to early postprandial hypoglycemia followed by late hyperglycemia. This pattern increases glycemic variability, complicates insulin dose adjustment, and contributes to oxidative stress and vascular risk. In this narrative review, we examine the current understanding of DGP pathophysiology and its clinical implications for insulin therapy. We discuss diagnostic strategies, nutritional interventions, and pharmacological treatments, with particular attention to insulin timing modulation. We also analyze the emerging role of diabetes technologies, including continuous glucose monitoring and automated insulin delivery systems, as well as future perspectives such as glucose-responsive insulins and regenerative approaches targeting gastric neuromuscular dysfunction. A mechanism-based, personalized therapeutic strategy may improve metabolic stability and patient outcomes.

Diabetes mellitus (DM) is increasingly recognized as a major risk factor for skeletal fragility, characterized by impaired bone quality and increased fracture susceptibility. Chronic hyperglycemia induces metabolic stress, oxidative injury, and low-grade inflammation, all of which disrupt normal bone remodeling. Accumulating evidence indicates that pyroptosis, a highly inflammatory form of programmed cell death, has emerged as a critical mechanistic link between diabetes and bone loss. Pyroptosis is driven by inflammasome activation, particularly the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, leading to caspase-1 activation, gasdermin-mediated membrane pore formation, and the release of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and interleukin-18 (IL-18). In the diabetic bone microenvironment, pyroptosis affects all major bone cell types. Osteoblast pyroptosis suppresses bone formation, osteoclast-associated pyroptotic signaling enhances bone resorption, and osteocyte pyroptosis disrupts mechanotransduction and microarchitectural integrity. Emerging data further reveal extensive crosstalk between pyroptosis, apoptosis, and necroptosis through PANoptotic signaling pathways, amplifying inflammatory bone damage. Experimental evidence from in vivo and in vitro models, together with emerging biomarker studies, consistently supports a central role for pyroptosis in diabetes-associated bone disease. Understanding the molecular regulation and temporal dynamics of pyroptosis in bone may provide novel therapeutic opportunities to preserve skeletal health in diabetic patients.

Diabetic retinopathy (DR), a common microvascular complication of diabetes mellitus, is a leading cause of vision loss among working-age adults. Although N6-methyladenosine (m6A), a prevalent post-transcriptional mRNA modification, is emerging as a key regulator in DR, the specific role of the m6A writer RBM15 in hyperglycemia-induced retinal endothelial cell injury remains poorly defined. Here, we found that RBM15 is upregulated in the retinas of diabetic mice as well as in endothelial cells (ECs) challenged with high glucose (HG). Knockdown of RBM15 significantly mitigated HG-induced apoptosis and rescued autophagy deficiency in retinal ECs. In vivo, downregulation of RBM15 effectively attenuated retinal thinning, acellular capillary formation, and vascular leakage in diabetic mice. Mechanistically, we demonstrated that RBM15 regulates HG-induced apoptosis and autophagy deficiency in ECs by modulating FOXO3 mRNA stability in an m6A-dependent manner. In conclusion, our findings identify the RBM15/m6A/FOXO3 signaling pathway as a critical regulator of HG-induced retinal microvascular dysfunction and highlight RBM15 as a potential therapeutic target for the treatment of DR.

Background Evidence on thrombectomy outcomes for posterior circulation tandem occlusions (TOs) is mostly from small single-center series. Purpose To evaluate thrombectomy outcomes in posterior circulation TOs. Materials and Methods Data from consecutive patients from 15 North American centers (February 2016 to October 2023) who underwent thrombectomy for posterior circulation TOs-defined as intracranial vertebral artery, basilar artery, or posterior cerebral artery occlusion with concurrent proximal extra- or intracranial vertebral artery stenosis or occlusion-were retrospectively analyzed. Baseline clinical, imaging, and procedural variables were summarized. Primary and clinical outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] score ≥ 2b), safety outcomes (symptomatic intracranial hemorrhage [sICH] and procedure-related complications), and 90-day functional outcome (modified Rankin Scale [mRS] score). Univariable and multivariable logistic regression was used to identify factors associated with favorable outcomes. Results Among 123 patients (median age, 63 years [IQR, 55-72 years]; 77 male patients), median National Institutes of Health Stroke Scale (NIHSS) score was 17 (IQR, 9-28). Intravenous thrombolytics were administered in 37 of 123 (30.1%) patients, and 97 of 123 (78.9%) underwent general anesthesia. Combined stent retriever and aspiration was the most common distal thrombectomy technique (45 of 123 [36.6%]), then aspiration (40 of 123 [32.5%]). Rescue stenting was required in 48 of 123 (39.0%) patients, more for proximal than distal lesions (44 of 123 [35.8%] vs nine of 123 [7.3%]; P = .01). Median puncture-to-reperfusion time (ie, from groin puncture to mTICI score ≥ 2b) was 50 minutes (IQR, 31-91 minutes). Successful reperfusion occurred in 108 of 122 (88.5%) patients, and sICH occurred in 11 of 123 (8.9%). At 90 days, 55 of 117 (47.0%) patients had a favorable outcome (mRS score of 0-3), and 37 of 117 (31.6%) had died. Distal-first strategy (ie, distal lesion thrombectomy first) was associated with shorter puncture-to-reperfusion time (P = .02) and lower incidence of sICH (P = .04); "dirty road" technique was associated with rescue stenting (P = .04). In multivariable analysis, hyperglycemia (P = .03), hypertension (P = .046), higher baseline mRS score (P = .008), and higher presentation NIHSS score (P = .03) predicted unfavorable functional outcome (mRS score of 4-6), whereas prestroke antithrombotic use (P = .006), monitored anesthesia care (P = .03), successful reperfusion (P = .02), and distal-first strategy (P = .01) predicted favorable functional outcome. Conclusion Thrombectomy for posterior circulation TOs was feasible and effective, with favorable outcomes associated with the distal-first strategy. © RSNA, 2026 Supplemental material is available for this article.

In contemporary epidemiology, the complex relationship between metabolic syndrome (MetS) and cancer risk has attracted considerable research attention. Gastric cancer (GC) is of particular concern due to its high mortality rate and significant global health impact. This concise narrative review, focusing on human observational and genetic studies, synthesizes recent clinical research findings to explore the connection between MetS and GC, emphasizing the underlying biological mechanisms and population-specific variations. It also addresses methodological considerations, research gaps, and implications for clinical practice and future research.

Chronic diabetic wounds are often characterized by hyperglycemia, infection susceptibility, and prolonged oxidative stress, facing the clinical challenge of delayed healing. Here, we present a cascade nanozyme-hydrogel platform that addresses these issues by integrating NiAl layered double hydroxide (LDH), glucose oxidase (GOx), and a hyaluronic acid-lipoic acid (HALA) hydrogel. This system independently metabolizes glucose and dynamically modulates the wound microenvironment. GOx catalyzes the conversion of excess glucose into gluconic acid and hydrogen peroxide (H2O2), acidifying the local microenvironment. The peroxidase-like (POD-like) activity of the NiAl LDH is activated under acidic conditions, selectively generating strong oxidizing hydroxyl radicals (•OH) for targeted antibacterial action. Once the infection resolves and the glucose levels normalize, the diminishing acidity shifts the system to a reparative mode. The anti-inflammatory properties of the HALA hydrogel scavenge residual reactive oxygen species (ROS) and promote tissue regeneration. In vitro experiments confirm the dynamic glucose- and pH-responsive functional adaptation. In vivo diabetic rat models verify that the LDH-GOx@HALA hydrogel can regulate the microenvironment of wounds in a direction conducive to accelerated healing. This work introduces an environmentally benign strategy of exploiting key pathological factors as endogenous triggers to dynamically reconstruct a healing-favorable microenvironment for intelligent wound management.