Search Results (12,606)

Background/Objectives: Regular physical exercise is strongly recommended for individuals with type 1 diabetes mellitus (T1DM) because of its beneficial effects on cardiovascular fitness, insulin sensitivity, metabolic control, and overall health. Nevertheless, participation in physical activity remains limited, largely due to the fear of exercise-induced hypoglycemia and glycemic instability. Glycemic responses to exercise in T1DM are influenced by the interaction between exercise modality, circulating insulin levels, nutritional status, and diabetes technologies. Continuous aerobic exercise, resistance training, high-intensity interval exercise, and mixed intermittent activities elicit distinct metabolic and hormonal responses, resulting in heterogeneous glycemic trajectories. This narrative review aimed to provide a clinically oriented synthesis of the physiological mechanisms underlying exercise-related glycemic fluctuations in T1DM and to discuss integrated insulin- and carbohydrate-based strategies to support safer participation in physical activity in the context of modern diabetes technologies. Methods: A structured narrative review was conducted using PubMed/MEDLINE, Scopus, and complementary searches in Google Scholar to identify experimental studies, observational studies, systematic reviews, consensus statements, and clinical guidelines focused on exercise-related glycemic responses in individuals with T1DM. Only articles published in English were considered. Evidence was selected and synthesized according to relevance to exercise modality, insulin therapy strategies, carbohydrate management, and diabetes technologies, including continuous glucose monitoring, continuous subcutaneous insulin infusion, and automated insulin delivery systems. The final narrative synthesis was based on 44 selected studies, reviews, consensus statements, and guidance documents considered most relevant to the objectives of this narrative review. Results: Available evidence indicates that continuous moderate-intensity aerobic exercise is most consistently associated with progressive glucose declines and increased risk of hypoglycemia, particularly when performed in the presence of elevated insulin on board. In contrast, resistance exercise and short-duration high-intensity or anaerobic exercise more frequently induce stable glycemia or transient hyperglycemia through adrenergic stimulation and increased hepatic glucose output. Mixed and intermittent exercise modalities often produce more variable responses depending on exercise sequencing, nutritional status, and insulin exposure. Across studies, integrated adjustment of basal and prandial insulin doses together with individualized carbohydrate supplementation emerged as the most effective strategy to reduce exercise-related glycemic instability. Continuous glucose monitoring and insulin pump technologies improved glucose trend awareness and management flexibility; however, physical exercise remains a challenging condition for current automated insulin delivery algorithms and still requires active user-driven decision-making. Conclusions: Exercise management in T1DM should be based on an individualized interpretation of exercise modality, glucose trends, insulin exposure, and nutritional context rather than on fixed glucose thresholds alone. Combining anticipatory insulin adjustments, tailored carbohydrate strategies, and appropriate use of diabetes technologies may substantially reduce glycemic variability and improve confidence toward physical activity participation. Structured education and individualized clinical guidance remain essential to translate physiological knowledge into effective real-world exercise management. Full article

The VHL–HIF-1α–VEGF axis regulates angiogenesis and metabolism. Beyond oncology, pVHL is essential for pancreatic β-cell function and is reduced in hypercaloric diet (HCD)-induced type 2 diabetes mellitus (T2DM). This study aimed to overexpress pVHL in pancreatic tissue and evaluate its effects on blood glucose levels and the expression of proteins related to glucose metabolism in the pancreas. HCD-induced diabetic C57BL/6 and BALB/c mice received a single intrapancreatic injection of an adenoviral vector (1 × 10¹² viral particles) encoding the murine Vhlh gene (AdVHL) to induce transient pVHL overexpression. The glycemic delta (post-load glucose minus fasting) and net incremental area under the curve (niAUC) were determined on days 3, 6, 9, 12, and 15 post-treatment, as the peak in GFP overexpression (used as a surrogate reporter of transduction efficiency) was detected between days 9 and 12. Immunohistochemistry (IHC) and immunofluorescence (IF) were used to assess the expression of pVHL, HIF-1α, GLUT-1, GLUT-2, and insulin in pancreatic tissue. AdVHL treatment significantly decreased the glycemic delta and niAUC in mice with T2DM (p < 0.01). On day 15 after treatment, HIF-1α and GLUT-1 expression were markedly reduced in AdVHL-treated mice (p < 0.01), while GLUT-2 and insulin were significantly increased (p < 0.01). These results were reproduced in both mouse strains. Transient overexpression of pVHL in pancreatic tissue of mice with T2DM was associated with decreased glucose levels and changes in the expression of proteins related to glucose metabolism in the pancreas, resembling a healthier phenotype than that of mice with T2DM. These findings support an important functional role of the pVHL–HIF-1α axis in pancreatic physiology, provide a proof-of-concept for further mechanistic and translational studies, and implicate pVHL in the altered glucose metabolism observed in T2DM. Full article

Background: The immune mechanism of diabetic kidney disease (DKD) has not yet been fully elucidated. This study aimed to characterize circulating lymphocyte subsets in patients with type 2 diabetes mellitus (T2DM), with a particular focus on DKD-related immune alterations and prognosis. Methods: Circulating T cells, B cells and NK cells were identified by flow cytometry. The primary endpoint was all-cause mortality, and overall survival was defined as the time from enrollment to death from any cause or last follow-up. Associations between lymphocyte subsets, inflammatory indices and renal function parameters were analyzed. Cox regression was used to identify factors associated with overall survival in patients with DKD and in the whole T2DM cohort. A prognostic nomogram was developed in the whole T2DM cohort to estimate 1-, 2-, 3-, and 5-year overall survival (OS) probabilities. Model performance was evaluated using the concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Mendelian randomization (MR) was performed as a further exploratory analysis to assess whether immune-related traits were genetically associated with DKD susceptibility, with inverse variance weighting (IVW) as the primary analytical method. Results: In total, 74 T2DM patients were divided into DKD (stage 3–4 of chronic kidney disease) and non-DKD groups. Median follow-up duration was 34.6 months. DKD patients exhibited elevated levels of NK cells, the monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). In patients with DKD, higher PLR and serum creatinine (SCr) were associated with poorer overall survival, whereas CD4⁺CD25⁺ T cell frequency was not significant after adjustment. In the whole T2DM cohort, higher frequency of circulating CD4⁺CD25⁺ T cells were associated with improved survival (HR 0.920, 95% CI 0.858–0.986, p = 0.019), whereas elevated PLR and SCr were linked to poorer outcomes. The exploratory nomogram incorporating CD4⁺CD25⁺ T cells, PLR, and SCr, showed acceptable internal performance in this cohort. As a separate exploratory analysis, MR suggested that genetically proxied CD4 expression on activated CD4 regulatory T cells was associated with a lower risk of DKD. Conclusions: DKD was associated with higher mortality and elevated MLR-, NLR-, PLR-, and NK cell levels in patients with T2DM. In patients with DKD, PLR and SCr were associated with overall survival, supporting the prognostic relevance of systemic inflammation and renal dysfunction. Individual lymphocyte subsets were not independently associated with survival in the DKD cohort after adjustment, whereas CD4⁺CD25⁺ T cell frequency provided additional prognostic information in the whole extended T2DM cohort analysis. Further validation is warranted. Full article

Background: Pre-existing diabetes mellitus is prevalent among critically ill adults and can influence initial glycemic targets, therapeutic decisions, and early risk stratification in the intensive care unit (ICU). However, diabetes status may be distributed across heterogeneous electronic health record (EHR) sources and may be incomplete at the time of ICU admission, particularly for inter-facility transfers. Methods: Using the public WiDS Datathon 2021 tabular release derived from the Global Open-Source Severity of Illness Score (GOSSIS) initiative, we conducted a retrospective machine-learning benchmarking study for admission-time identification of documented diabetes status in ICU patients. Candidate predictors included demographics, admission characteristics, anthropometrics, day-1 physiologic and laboratory summaries, APACHE-related variables, comorbidity indicators, and site descriptors. We compared CatBoost, random forest, tuned XGBoost, tuned LightGBM, histogram-based gradient boosting, and a soft-voting ensemble combining XGBoost, LightGBM, and histogram-based gradient boosting. Because class imbalance was a central concern, the final workflow emphasized model-intrinsic class weighting and threshold-aware evaluation rather than synthetic oversampling. Results: In the primary leakage-mitigated random validation split, the voting ensemble achieved the highest overall balance, with AUROC 0.8539, precision 0.5671, recall 0.6690, and F1-score 0.6138. Tuned LightGBM was the most sensitivity-oriented individual model, achieving recall 0.7677 and AUROC 0.8537, although with lower precision and a less favorable Brier score. Ablation analyses clarified the source of this performance: removing leakage-prone and APACHE-related variables caused only modest decreases in discrimination, whereas the strict reduced model that also excluded glucose-like predictors produced a marked decline, with LightGBM AUROC falling to 0.7432 and the voting ensemble AUROC falling to 0.7448. These findings, together with SHAP analyses identifying day-1 glucose maximum, day-1 glucose minimum, BMI, age, hemoglobin, and related clinical variables as major contributors, indicate that glucose-related admission variables remained the dominant predictive signal. In grouped hospital validation, tuned LightGBM maintained recall of 0.7684 while AUROC decreased modestly to 0.8443, indicating preserved case detection under stricter site separation but reduced precision. Precision–recall analysis further showed that average precision decreased from 0.622 under random validation to 0.551 under grouped validation; at a high-sensitivity grouped-site operating point, a probability threshold of 0.4537 achieved recall of 0.8001 with precision of 0.4314. Calibration curves and Brier scores showed that predicted probabilities were imperfectly calibrated. Conclusions: Although the dominance of glucose-related predictors is clinically plausible for identifying documented diabetes status, early glycemic measurements in critically ill patients may also partly capture acute stress physiology, treatment-related effects, monitoring intensity, or other forms of acute dysglycemia rather than chronic diabetes status alone. Therefore, these findings support gradient-boosted and ensemble models as reproducible tools for ICU admission-time phenotyping of documented diabetes status, but the proposed system should be interpreted primarily as a screening-oriented phenotyping aid for chart review, cohort enrichment, or workflow support, not as a stand-alone diagnostic tool. Further external validation, recalibration, threshold selection matched to intended use, and clinical review are needed before deployment. Full article

Background and Objectives: Diabetic peripheral neuropathy (DPN) is a common and debilitating complication of obesity and type 2 diabetes (T2D) affecting up to 50% of patients with long-standing disease. While chronic hyperglycemia plays a central role in its pathogenesis, intensive glycemic control provides only partial protection, suggesting the involvement of additional metabolic pathways. The primary objective of this systematic review was to evaluate the role of lipid metabolism disturbances and advanced lipidomic alterations in the development and progression of DPN in patients with obesity and T2D. Secondary objectives included identifying specific lipid species associated with DPN and exploring their potential pathophysiological and clinical implications. Methods: This systematic review included 8 studies that met the inclusion criteria and was conducted according to PRISMA guidelines and registered in PROSPERO/2026/CRD420261288920. Study quality was assessed using the Newcastle–Ottawa Scale. Results: Large population-based cohorts reported a consistent association between hypertriglyceridemia and DPN prevalence, with triglyceride levels >204 mg/dL associated with an approximately 40% increased risk. Lipidomic analysis revealed alterations in acylcarnitine, sphingolipids, and phospholipids. However, the evidence remains limited and heterogeneous, and neuropathy-specific outcomes were insufficiently evaluated in interventional studies. Conclusions: Lipid metabolism disturbances, particularly hypertriglyceridemia and specific lipidomic alterations, may contribute to DPN beyond the effects of hyperglycemia. Although not yet clinically actionable, lipidomic alterations may represent promising future biomarkers and therapeutic targets in DPN. However, the current evidence is limited by heterogeneity and predominantly observational designs. Further well-designed longitudinal and interventional studies are needed to clarify causal relationships and clinical relevance. Full article

Background and Aims: Type 2 diabetes mellitus is a recognized risk factor for hepatocellular carcinoma (HCC), particularly in the setting of metabolic dysfunction-associated steatotic liver disease (MASLD), chronic viral hepatitis, advanced fibrosis, and cirrhosis. Beyond hyperglycemia and insulin resistance, diabetic hepatocarcinogenesis is shaped by metabolic inflammation, lipotoxicity, oxidative stress, fibrogenic remodeling, and the cirrhosis-dysplasia-HCC continuum. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) may influence several hepatometabolic pathways, but the epidemiologic evidence linking SGLT2i use to HCC risk remains heterogeneous. Methods: We conducted a systematic review and meta-analysis of observational studies evaluating SGLT2i exposure and incident HCC in adults with type 2 diabetes. PubMed, Embase, and the Cochrane Library were searched up to 15 March 2026. Adjusted time-to-event estimates were pooled using a restricted maximum likelihood (REML) random-effects model. The certainty of evidence was assessed using the GRADE framework and judged to be very low. Results: Six observational studies including 526,446 participants were included. SGLT2i exposure was associated with a lower observed risk of incident HCC (pooled HR 0.59, 95% CI 0.45–0.77), but between-study heterogeneity was substantial (I² = 75.2%, τ² = 0.074). The association remained directionally similar after exclusion of Huynh et al. (HR 0.61, 95% CI 0.45–0.81) and in a DPP-4 inhibitor-restricted active-comparator analysis (HR 0.60, 95% CI 0.39–0.92). However, the 95% prediction interval crossed the null (0.25–1.37), indicating that future comparable studies may plausibly show no protective association. Conclusions: SGLT2i exposure was associated with a lower observed risk of incident HCC across available observational studies. However, the certainty of evidence was judged to be very low, and substantial heterogeneity, comparator variation, mixed time-to-event estimands, residual confounding, and a prediction interval crossing the null preclude causal interpretation. These findings should be considered hypothesis-generating rather than practice-changing evidence and support further hepatology-oriented validation. Full article

Diabetes Mellitus is a chronic metabolic disorder characterized by elevated blood glucose due to defects in insulin secretion or action, or both, leading to serious short- and long-term complications if not effectively managed. However, there is limited qualitative evidence exploring how youths diagnosed with Type 1 Diabetes Mellitus (T1DM) experience disease onset, management, complications, emotional adaptation, and education within the South African public healthcare system. The study aims to investigate the lived experiences of youths living with T1DM in a selected public hospital in Limpopo province, South Africa. The objectives were to explore and describe the lived experiences of youths living with T1DM. A qualitative, explorative, descriptive, and contextual design was used to gain a thorough understanding of the experiences of youths living with T1DM. A non-probability sampling technique was used to select 12 participants using a pre-determined criterion. Data were collected through individual semi-structured interviews using an interview guide. The data were analyzed using Colaizzi’s method, where themes and sub-themes were developed with the inclusion of an independent coder. Measures to ensure trustworthiness and ethical considerations were adhered to throughout the study. The findings revealed that, despite the participants sharing the same diagnosis, they experience multiple interrelated barriers that significantly hindered effective self-care management, such as limited access to diabetic diet, glucometers and supplies, treatment and informational-related barriers, school-related challenges, transportation constraints and inadequate social support. Furthermore, the findings highlighted gaps in early recognition of symptoms, standardized diabetes education, psychosocial support, and continuity of care. The study recommends the need for holistic, patient-centred, and contextualized interventions that do not only address medical management but the socioeconomic, educational, and psychological needs of youths. Full article

Of the many clinical phenotypes of obesity, the most prevalent are metabolically “healthy” (MHO) and metabolically “unhealthy” (MUO) obesities, the latter being associated with a range of comorbidities, including type 2 diabetes mellitus (T2DM). The underlying causes of different obesity phenotypes and the mechanisms of conversion of one phenotype into another have yet to be fully elucidated. However, increasing evidence suggests the key role of low-grade metabolic inflammation (metaflammation) in the pathogenesis of obesity and metabolic dysfunction. The review presents a comprehensive description of changes in immune cell populations and pro-inflammatory mediators, as well as a detailed comparative mapping of the adipose tissue immune landscape during MHO/MUO transition. Based upon a conceptual model for the intensification of metaflammation during MHO progression and conversion to MUO, a pattern of dynamical changes that accompany MHO/MUO transition is described. Though many parameters demonstrate significant differences in multiple cross-sectional and some longitudinal studies, only a few of them (CRP, IL-6, IL-17A, absolute counts of leukocytes and neutrophils) meet the criteria of a validated biomarker in clinical setting. A lack of standardization in MHO definition and heterogeneity in the severity of MUO make the search for predictive biomarkers a challenge. The review also discusses the mechanisms underlying metabolic memory and the incomplete reversibility of metabolic disturbances after bariatric surgery. Full article

Background: Gestational diabetes mellitus (GDM) is associated with metabolic disturbances extending beyond glucose homeostasis, including alterations in lipid metabolism. However, evidence on the fatty acid composition of maternal serum lipids in GDM remains inconsistent, and data on placental fatty acid transfer are limited. This study aimed to explore associations between maternal serum lipid fatty acid composition, selected FA indices, and transplacental transfer of fatty acids derived from maternal serum lipids in pregnancies complicated by GDM. Methods: A cross-sectional study was conducted among 139 pregnant women, including 104 healthy controls and 35 women with GDM. Maternal serum and umbilical cord blood samples were collected at delivery. FA composition was analyzed using gas chromatography. Selected FA indices and the transplacental transport index (TTI) were calculated. Statistical analyses included group comparisons, multivariable models adjusted for maternal age and pre-pregnancy BMI, and false discovery rate correction. Results: Modest differences were observed in selected fatty acids and FA indices, particularly palmitoleic acid (C16:1) and the C16:1/C16:0 ratio. Principal component analysis suggested partial separation between groups, although substantial overlap was present. A difference in transplacental transport was observed for α-linolenic acid; however, high variability was noted. No consistent associations between reported dietary patterns and fatty acid composition of circulating serum lipids were identified. Conclusions: This exploratory study suggests potential differences in fatty acid composition and selected indices in GDM; however, findings should be interpreted with caution. The observed patterns may reflect late-pregnancy metabolic adaptations rather than causal mechanisms. Further studies in larger and more diverse populations are required to confirm these findings. Full article

Type II diabetes mellitus (T2DM), a chronic metabolic disorder characterized by insulin resistance, is often accompanied by dysregulated bile acid metabolism. Although gastrodin, a bioactive compound derived from Gastrodia elata, has demonstrated potential in diabetes management, its therapeutic mechanisms remain incompletely understood. The aim of this study is to investigate the therapeutic effects and potential mechanisms of gastrodin on T2DM mice from the perspective of bile acid metabolism. In this study, we found that gastrodin could not only reduce lipid accumulation, reduce inflammation, improve antioxidant capacity, alleviate oxidative stress, change the composition of intestinal flora, and improve the disorder of flora caused by the disease in T2DM mice, but also target Yin yang 1 (YY1) to reduce the expression level of YY1 in the liver under a high-fat diet condition. At the same time, YY1 negatively regulates the expression level of Farnesoid X Receptor (FXR), which increases the expression level of FXR, inhibits the enzyme activity of Cholesterol-7α-hydroxylase (CYP7A1) through Small Heterodimer Partner (SHP), reduces the production of chenodeoxycholic acid (CDCA) in the liver, and further affects the production of secondary bile acids through liver–intestinal circulation, promoting the secretion of Glucagon-Like Peptide-1 (GLP-1) and insulin, thereby reducing blood glucose. At the same time, combined with the results of HE staining, gastrodin can reduce the pathological damage of the liver and pancreas in type II diabetic mice, repairing their normal morphology and function. It provides a direct pathological basis for the improvement of diabetes and liver complications, provides theoretical support for the subsequent research and development of precision targeted drugs, provides experimental basis for the development of new natural hypoglycemic drugs, and promotes the transformation and application of the modernization of traditional Chinese medicine in the field of metabolic diseases. Full article

Background: Solid pseudopapillary neoplasms of the pancreas (SPN-P) are rare, low-grade malignancies primarily affecting young women. While surgical resection is definitive, the optimal balance between oncological radicality and functional preservation remains a clinical challenge. This study evaluates tailored surgical strategies utilizing minimally invasive and parenchyma-preserving techniques. Patients and Methods: We conducted a multi-institutional retrospective analysis of SPN-P cases treated between March 2020 and May 2023. Out of 167 pancreatic resections, five paradigmatic cases were identified. We analyzed the decision-making process for preoperative staging (CT/MRI/EUS-FNB), surgical approach (open, laparoscopic, or robotic), and the implementation of parenchyma-preserving versus formal resections. Results: The cohort included four females and one male (mean age 40.6 years; range 13–73). Surgical approaches were tailored to tumor location and patient characteristics: two patients underwent pancreatoduodenectomy (one laparotomic, one laparoscopic), two underwent distal pancreatectomy (one robotic, one laparoscopic), and one pediatric patient underwent laparoscopic parenchyma-preserving central pancreatectomy. R0 resection was achieved in all cases. No Grade B/C postoperative pancreatic fistulas (POPF) or complications Clavien-Dindo ≥III occurred. At a mean follow-up (FU) of 38.4 months (range 20–58), the disease-free survival rate was 100%. One patient developed new-onset diabetes mellitus following distal pancreatectomy. Conclusions: A tailored surgical approach—integrating robotic, laparoscopic, and parenchyma-preserving techniques—may enable excellent oncological outcomes while minimizing morbidity. For SPN-P, the choice of procedure should prioritize the preservation of pancreatic function, particularly in young patients, without compromising surgical margins. Full article

Background: Retinal and optic nerve disorders remain major causes of visual morbidity worldwide. Ocular fundus flavoprotein fluorescence (FPF) imaging has emerged as a potential noninvasive biomarker of mitochondrial dysfunction for earlier detection and evaluation of disease severity. Methods: We conducted a Systematic Scoping Review of the diagnostic and correlational utility of quantitative FPF parameters in retinal and optic nerve diseases compared with healthy controls. Following PRISMA-ScR guidelines, we searched MEDLINE, Web of Science, Scopus, and CENTRAL for peer-reviewed human studies available online before 31 December 2025. Results: Seventeen studies were included, encompassing 1914 eyes and 1339 participants, and were predominantly cross-sectional. In healthy eyes, mean macular and optic nerve head FPF intensity were reported as 24.1 ± 12.2 gsu and 30.6 ± 14.6 gsu, respectively. Higher signals were reported in several disorders, including diabetes mellitus (76.0 [67.0–92.0] gsu), neovascular age-related macular degeneration (67.47 ± 17.77 gsu), and retinitis pigmentosa (50.5 ± 12.2 gsu). However, lower, unchanged, or stage-dependent signals were also observed within the same disease categories. Interpretation across studies was limited by substantial heterogeneity in patient selection, disease definitions, imaging protocols, control groups, and FPF outcome metrics. The precise cellular and sublayer origin of the detected signal also remains challenging to determine. Conclusions: Ocular fundus FPF imaging provides promising metabolic insight into retinal and optic nerve diseases. However, current evidence remains heterogeneous and largely cross-sectional, limiting clinical interpretability and generalizability. Longitudinal studies, technical standardization, and multimodal integration are needed to define reproducible disease-specific FPF profiles and improve translational applicability. Full article

Diabetes mellitus (DM), particularly Type 2 DM (T2DM), is increasingly recognized as both a risk factor and an early manifestation of pancreatic ductal adenocarcinoma (PDAC), yet the molecular mechanisms bridging these conditions remain poorly understood. There is growing evidence that chronic metabolic stress in diabetes induces persistent cellular reprogramming and metabolic memory through stable post-translational and epigenetic alterations, independent of conventional insulin resistance, obesity, and inflammatory pathways. We aim to elucidate how hyperglycaemia and metabolic overload contribute to the accumulation of major intermediates, such as acetyl-CoA, Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), and reactive oxygen species, which induce broad changes in post-translational modifications in diabetes-induced PDAC. A comprehensive literature search was conducted using electronic databases, including PubMed, Scopus, and Web of Science databases, to retrieve studies published between 2005 and 2025. This review synthesizes current understanding of post-translational modifications (PTM) dynamics in diabetes-associated PDAC, with emphasis on their role in modulating oncogenic pathways such as KRAS-MAPK and PI3K-AKT. We introduce the concept of PTM remodeling, wherein transient metabolic perturbations become persistently stabilized, contributing to metabolic memory and tumor initiation. In addition, we examine how PTM-driven alterations influence the pancreatic tumor microenvironment, including stromal activation, immune evasion, and metabolic crosstalk, reinforcing a bidirectional link between tumor progression and systemic metabolic dysfunction. Furthermore, emerging therapeutic strategies targeting PTM-regulating enzymes, metabolic substrates, and signaling nodes are discussed as potential approaches to disrupt this axis. Collectively, precision targeting of PTM-mediated metabolic reprogramming represents a promising framework for early intervention and therapeutic development in PDAC associated with diabetes. Full article

Background/Objectives: Acute pancreatitis is increasingly recognized as a risk factor for disturbances in glucose metabolism and the development of diabetes mellitus (DM). However, the long-term endocrine consequences of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remain poorly characterized. This study aimed to evaluate the association between post-ERCP pancreatitis and the risk of new-onset diabetes mellitus (NODM). Methods: This retrospective cohort study included patients who underwent ERCP between 2019 and 2024 at a tertiary referral center. New-onset diabetes mellitus was defined using laboratory data and International Classification of Diseases (ICD) diagnostic codes within one year after ERCP. Multivariable logistic regression adjusting for age, sex, hypertension, and coronary artery disease was performed. Results: A total of 2695 patients were included. Post-ERCP pancreatitis occurred in 165 patients (6.1%). New-onset diabetes developed in 9/165 patients (5.5%) in the PEP group and in 27/2530 patients (1.1%) in the non-PEP group. An increased incidence of new-onset diabetes was observed among patients who developed post-ERCP pancreatitis (crude OR 5.35, 95% CI 2.47–11.57; p < 0.001). In multivariable analysis adjusting for age, sex, hypertension, and coronary artery disease, post-ERCP pancreatitis remained significantly associated with new-onset diabetes in the fully adjusted model (adjusted OR 5.33, 95% CI 2.42–11.77; p < 0.001). The absolute risk increase was 4.39%, corresponding to a number needed to harm of 23. Conclusions: An increased incidence of new-onset diabetes was observed among patients who developed post-ERCP pancreatitis. This association remained significant after adjustment for baseline cardiovascular comorbidities. Although the absolute risk increase was modest, these findings may be clinically relevant. Because this was a retrospective study with a limited number of diabetes cases, the findings should be considered hypothesis-generating and require confirmation in prospective studies. Full article