Search Results (3,308)

Background: Achieving remission of type 2 diabetes mellitus (T2DM) after bariatric surgery represents a critical opportunity to reduce long-term diabetes-related complications, including cardiovascular disease, nephropathy, neuropathy, and retinopathy. However, remission rates vary widely across patients, and identifying modifiable clinical and behavioral determinants remains essential for optimizing integrated metabolic care. Objectives: In the current study, we aimed to (1) classify type 2 diabetes mellitus (T2DM) remission status after bariatric surgery through clinical, anthropometric, and behavioral variables at follow-up; (2) identify the main model-based determinants of remission status and explainable machine learning using the preoperative model for baseline risk stratification with surgical candidates. Methods: We performed a retrospective cross-sectional study on 233 patients with T2DM who had bariatric surgery at a tertiary referral center. We made use of two analytical frameworks: a full-feature approach to identify the current remission status in a cross-sectional manner and a preoperative approach to make a temporal classification of the baseline for the first time. We trained and internally assessed 14 machine learning and deep learning classifiers. We evaluated model interpretability using SHAP. Results: In the full-feature cross-sectional classification, the Bottleneck Network performed best (ROC AUC = 0.889). SHAP data identified percentage weight regain, pre- and post-surgical body mass index, HbA1c, and oral hypoglycemic agent use as the dominant model-associated factors. In the restricted preoperative setting, the Extra Trees model achieved an AUC of 0.707, which is a lower level but still represents good baseline risk stratification performance. Conclusions: The findings indicate that remission status after bariatric surgery is both clinical as well as behavioral, but the post-operative or contemporaneously assessed variables should be looked at as classification (as opposed to prediction) models. The preoperative model may be able to be used in risk stratification, but clinical validation and prospective evaluation should be made prior to clinical implementation. Full article

Background/Objectives: Glucagon-like peptide-1 (GLP-1) receptor agonists and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists are used long term for obesity and diabetes, but their oesophageal safety is uncertain: weight loss may reduce Barrett’s oesophagus and adenocarcinoma risk, whereas delayed gastric emptying may worsen reflux. We performed a genetic assessment of target-mediated oesophageal safety. Methods: Two-sample drug-target Mendelian randomisation used cis-expression quantitative trait loci for both receptors (31,684 participants). Outcomes were European genome-wide association studies of gastro-oesophageal reflux disease and the Barrett’s oesophagus/oesophageal adenocarcinoma axis, with a trans-ancestry squamous cell carcinoma comparator. A prespecified gated workflow required positive-control validation, and target specificity required genetic colocalisation (posterior probability of a shared causal variant ≥ 0.70). Candidate metabolic mediators were examined in two-step analyses, and findings were replicated in an independent Finnish population (FinnGen R12). Results: Genetically proxied GLP-1 receptor expression was not associated with reflux disease (odds ratio 0.97, 95% confidence interval 0.85–1.11), arguing against a substantial target-mediated reflux liability; the GIP receptor estimate was not estimable. For the Barrett’s oesophagus/adenocarcinoma endpoint, estimates were near the null for both receptors (GLP-1R 0.96, 0.47–1.96; GIPR 1.00, 0.42–2.37); colocalisation was uninformative because the outcome loci carried no detectable association signal, and wide intervals did not exclude moderate effects. The null reflux findings were reproduced in FinnGen. Adiposity showed the most consistent pathway association, whereas glycaemic traits did not, including when HbA1c was instrumented from a population-based genome-wide association study providing an order of magnitude more variants. Conclusions: GLP-1 receptor perturbation was not associated with reflux disease, providing cautious genetic reassurance. For the Barrett’s oesophagus/adenocarcinoma axis, no target-specific association was demonstrated, but colocalisation was uninformative because the outcome loci carried no detectable signal, and imprecision precludes firm safety conclusions; larger adenocarcinoma-specific studies are warranted. Full article

Background: Gastrointestinal (GI) involvement is increasingly recognised in paediatric SARS-CoV-2 infection and multisystem inflammatory syndrome in children (MIS-C), but severe GI bleeding remains rare. Its pathogenesis in this setting is multifactorial: direct viral injury, hyperinflammatory microvascular damage, treatment-related mucosal injury, and coagulopathy may all contribute, and the relative role of each is often difficult to disentangle. Case Presentation: A previously healthy 12-year-old boy underwent appendectomy for perforated appendicitis with peritonitis. On postoperative Day 1, he developed high fever and was found to be SARS-CoV-2 PCR-positive; SARS-CoV-2 IgM and IgG were also positive. He met the positive clinical elements of the CDC 2023 case definition for MIS-C (persistent fever, multisystem involvement—gastrointestinal, hepatic, haematological, and markedly elevated inflammatory markers), although perforated appendicitis with peritonitis is a sufficient alternative explanation and the diagnosis cannot be regarded as secure (see Discussion). Treatment included broad-spectrum antibiotics (meropenem, amikacin, metronidazole), methylprednisolone 2 mg/kg/day, and intravenous immunoglobulin (IVIG) 2 g/kg. On Day 4 in the paediatric intensive care unit (PICU), the patient developed sudden haematemesis with fresh blood through the nasogastric tube and haemodynamic collapse. Coagulation studies revealed prolonged INR (1.6) and reduced prothrombin activity (42%). The patient was stabilised with packed red blood cells, fresh frozen plasma, and intravenous vitamin K. Fibrogastroscopy demonstrated diffuse mucosal bleeding without ulcers or anatomical defects; histology showed mucosal hyperaemia, mixed basal inflammation with intraepithelial lymphocytes, and small erosions. Melena persisted for several days. The child recovered fully and was discharged after 20 days with substantially improved but not fully normalised laboratory values (residual mild anaemia, Hb 110 g/L, and elevated CRP 32.7 mg/L and D-dimer 5.88 mg/L). Conclusions: Severe upper GI bleeding is a rare but life-threatening event in children with severe SARS-CoV-2 infection and MIS-C. In our case, several mechanisms may have acted in combination, although none could be confirmed individually: possible direct viral enterocyte injury via ACE-2 receptors, hyperinflammatory microangiopathy, high-dose corticosteroid-related mucosal injury, possible broad-spectrum antibiotic-associated vitamin K deficiency, and postoperative critical-illness stress. Their relative contributions cannot be determined from a single retrospective case. Bleeding occurred despite continuous PPI prophylaxis, suggesting that PPI cover alone is insufficient when multiple risk factors coexist; the clinical implication is that risk-factor-based (rather than universal) PPI prophylaxis, together with monitoring of vitamin K-dependent coagulation, should be considered in critically ill children receiving high-dose corticosteroids and prolonged broad-spectrum antibiotics. Full article

Background and Objectives: Cerebrovascular events remain among the most feared complications after transcatheter aortic valve implantation (TAVI). Whether early and post-discharge cerebrovascular events are associated with distinct clinical, echocardiographic, haemodynamic, and procedural predictors remains incompletely clarified. Materials and Methods: This retrospective, observational, two-center cohort study included 556 patients who underwent TAVI for severe symptomatic aortic stenosis between October 2011 and May 2023. The primary outcomes were in-hospital stroke and mid-to-long term stroke occurring after hospital discharge. Stroke diagnoses were established by neurological assessment and confirmed by cranial computed tomography and/or magnetic resonance imaging. Univariable comparisons and Firth penalized multivariable logistic regression analyses were performed to identify predictors of each outcome. Results: In-hospital stroke occurred in 14 patients (2.5%), whereas mid-to-long term stroke occurred in 16 patients (2.9%). In Firth penalized multivariable analysis, baseline mitral regurgitation grade (odds ratio [OR] 2.174, 95% confidence interval [CI] 1.299–3.638; p = 0.003), HbA1c (OR 1.644, 95% CI 1.111–2.433; p = 0.013), and prior cerebrovascular event (OR 4.269, 95% CI 1.150–15.846; p = 0.030) were independently associated with in-hospital stroke. For mid-to-long term stroke, post-dilatation (OR 9.862, 95% CI 2.555–38.067; p < 0.001) and very severe aortic stenosis phenotype (OR 3.649, 95% CI 1.343–9.916; p = 0.011) were independently associated with the outcome. Conclusions: Early and post-discharge cerebrovascular events after TAVI were infrequent but associated with distinct predictor profiles. In-hospital stroke was associated with baseline mitral regurgitation grade, HbA1c, and prior cerebrovascular event, whereas mid-to-long term stroke was associated with post-dilatation and very severe aortic stenosis phenotype. Given the limited number of events, these findings should be interpreted as exploratory and require validation in larger prospective cohorts. Full article

Background: Emergency Department (ED) viral hepatitis screening programs typically report short-term outcomes. We evaluated the medium-term impact of an ED-based screening for Hepatitis C (HCV), Hepatitis B (HBV), and Hepatitis D (HDV) viruses. Methods: Prospective opportunistic screening conducted between January 2020 and December 2024 at a referral hospital in Barcelona. Adults attending the ED were screened for HBV, HCV, and HDV. Positive cases were evaluated and linked to care when appropriate. To assess screening impact, HCV RNA and HBsAg prevalences were compared between 2020–2021 and 2023–2024 among participants aged ≤80 years. Results: Over five years, 39,532 individuals were screened: 220 (0.56%) had detectable HCV RNA, 234 (0.59%) HBsAg, and 4 HDV RNA. Of 110 patients with detectable HCV RNA eligible for linkage, 84 (76%) were treated and cured. Among 135 HBV-positive individuals eligible for linkage, 116 (86%) attended outpatient follow-up. HCV RNA prevalence significantly decreased (0.58% vs. 0.35%, p = 0.005), whereas HBsAg prevalence did not vary (0.7% vs. 0.58%, p = 0.224). Conclusions: Sustained ED-based screening enabled the identification and linkage to care of several individuals with HBV and HCV. This strategy contributed to a reduction in HCV prevalence among ED attendees and supports opportunistic ED screening in viral hepatitis elimination goals. Full article

Background and aims. Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease associated with cirrhosis, hepatocellular carcinoma, and increased risks of liver-related and cardiovascular mortality. Many patients, however, remain asymptomatic until advanced stages. The gamma-glutamyl transferase to high-density lipoprotein cholesterol (GGT/HDL-C) ratio is a simple, noninvasive marker reflecting hepatic dysfunction and cardiometabolic imbalance. This study assessed its association with NAFLD and determined an optimal cutoff for identifying NAFLD. Methods. We conducted a cross-sectional analysis of 575 adults undergoing routine health examinations at the University of Medicine and Pharmacy Hospital in Ho Chi Minh City between 2021 and 2023. Participants with significant alcohol intake, viral hepatitis, or other chronic liver diseases were excluded. NAFLD was diagnosed by standardized abdominal ultrasonography based on increased hepatic echogenicity relative to the renal cortex or spleen. Associations between GGT/HDL-C and NAFLD were assessed by logistic regression (both as a continuous variable and by quartiles), and diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Statistical significance was defined as a two-tailed p-value < 0.05. Results. Individuals with NAFLD showed significantly higher BMI, prevalence of hypertension and diabetes, and elevated glucose, HbA1c, AST, ALT, GGT, cholesterol, triglycerides, and LDL-C, along with lower HDL-C. Each unit increase in the GGT/HDL-C ratio was associated with a 2% increase in the odds of NAFLD based on univariate logistic regression analysis. However, after adjustment for demographic and metabolic covariates, the GGT/HDL-C ratio was no longer independently associated with NAFLD. The highest quartile had an odds ratio of 7.05 (95% CI: 4.2–11.83) compared to the lowest. The area under the ROC curve for GGT/HDL-C was 0.72, outperforming GGT or HDL-C alone. A cutoff of 32.47 UI/mmol had 72.4% sensitivity and 63.3% specificity. Conclusions. The GGT/HDL-C ratio showed a significant unadjusted association with NAFLD and moderate discriminatory performance. However, because the association was no longer significant after full adjustment, the ratio should currently be considered a simple laboratory-based screening marker that requires further validation before routine clinical application. Full article

Background/Objectives: The study aimed to investigate the significance of laboratory biomarkers, particularly the lactate-to-hemoglobin ratio at admission in predicting 30-day mortality in patients with acute upper gastrointestinal bleeding (UGIB). Methods: Patients who presented to the emergency department due to acute UGIB between January and December 2024 were included in the study. The laboratory parameters at the time of admission, medication usage, endoscopic diagnoses, and 30-day mortality rates of the patients were investigated. It was investigated whether there were differences in biochemical parameters such as hemoglobin, hematocrit, neutrophil, lymphocyte, platelet, international normalized ratio (INR), pH, lactate, blood urea nitrogen (BUN), creatinine, C-reactive protein (CRP), albumin, BUN to creatinine ratio, and lactate to hemoglobin ratio between patients with and without 30-day mortality. In addition, the relationship between mortality, drug use, and endoscopic diagnoses was examined. Results: A total of 241 patients participated in the study. Of the participants in the study, 79 (32.8%) were women and 162 (67.2%) were men. The average age of the patients was 70 years. The most common causes of bleeding were, in order, bulbar ulcer (n = 84, 34.9%) and gastric ulcer (n = 79, 32.8%). A total of 15 (6.2%) patients developed mortality within 30 days. In the mortality group, lymphocyte (p = 0.016) and albumin (p = 0.026) values were statistically low, while INR (p = 0.041), creatinine (p = 0.020), CRP (p < 0.01), lactate (p = 0.014) and lactate to Hb ratio (LHR) (p = 0.012) values were significantly high. In cases of bleeding due to malignancy, mortality was higher. No association was found between medication use and mortality. Conclusions: In this exploratory study, the LHR showed potential as an adjunctive biomarker for estimating 30-day mortality in patients with non-variceal acute UGIB. It can be readily calculated based on common laboratory values, does not necessitate complex scoring systems, and can help with quick risk assessment in emergency conditions. Large, multicenter prospective studies are required to confirm prediction accuracy as well as identify optimum cutoff values for clinical application. Full article

Undiagnosed diabetes and prediabetes are common among trauma patients and increase perioperative complication rates, yet routine glycemic screening at hospital admission is rarely performed. We compared 10 supervised machine learning (ML) algorithms for early detection of impaired glucose metabolism in 1789 trauma surgery patients (1095 normal; 694 prediabetes/diabetes) using questionnaire data and preoperative laboratory values within a nested cross-validation framework with hyperparameter optimization. On the combined feature set, XGBoost achieved the highest area under the receiver operating characteristic curve (ROC-AUC; 0.815), followed by multilayer perceptron (0.814) and Gradient Boosting (0.813); adding blood parameters significantly improved performance for nine of ten algorithms (DeLong’s test, p < 0.05). SHapley Additive exPlanations (SHAP) and XGBoost feature gains identified six overlapping predictors, yielding a simplified model with comparable mean discrimination. Inter-model differences were small, and a fully interpretable logistic regression model remained within one percentage point of XGBoost. The best-performing model demonstrated strong calibration and a higher net benefit than either universal testing or no testing across the evaluated threshold probabilities. In routine trauma practice, such a model could identify patients who would benefit from confirmatory glycated hemoglobin (HbA1c) testing, enabling earlier detection of dysglycemia, risk-stratified glucose management, and timely referral for lifestyle intervention in patients with prediabetes. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders during pregnancy and is associated with adverse maternal and neonatal outcomes. Xenopsin-Related Peptide-1 (XRP-1) has recently emerged as a potential regulator of glucose metabolism and insulin homeostasis. This study evaluated serum XRP-1 levels and assessed their diagnostic performance in women with GDM. Methods: In this prospective observational study, 120 pregnant women between 24 and 28 weeks of gestation were enrolled, including 60 women with GDM and 60 healthy controls. Serum XRP-1 concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). Clinical, biochemical, and obstetric characteristics were compared between groups. Receiver operating characteristic (ROC) curve analysis and multivariable logistic regression were performed to evaluate the diagnostic performance and independent association of XRP-1 with GDM. Results: Serum XRP-1 levels were significantly higher in women with GDM than in healthy controls (3.45 ± 0.47 vs. 2.87 ± 0.46 ng/mL, p = 0.003). ROC analysis demonstrated moderate discriminatory performance for XRP-1 in identifying GDM (AUC = 0.658, 95% CI: 0.560–0.750), with an optimal cut-off value of 3.12 ng/mL, corresponding to 63.3% sensitivity and 61.7% specificity. Multivariable logistic regression demonstrated that serum XRP-1 remained independently associated with GDM after adjustment for maternal age, pre-pregnancy body mass index, gestational weight gain, and parity (adjusted OR 2.74, 95% CI 1.31–5.73; p = 0.007). HbA1c and C-reactive protein levels were also significantly higher in the GDM group. Conclusions: Serum XRP-1 concentrations were independently associated with GDM and demonstrated moderate diagnostic accuracy. Although XRP-1 cannot replace established diagnostic methods, it may represent a complementary biomarker for identifying gestational dysglycemia. Larger multicenter studies are required to validate its clinical utility. Full article

Background/Objectives: This 12-week randomized controlled trial investigated whether progressive resistance training combined with vitamin D supplementation produces enhanced combined improvements in cardiometabolic profiles and functional capacities compared with monotherapies in elderly Korean women with type 2 diabetes mellitus (T2DM) and vitamin D deficiency. Methods: In a 2 × 2 factorial design, 52 women (aged 65–80 years) with T2DM and serum 25(OH)D < 20 ng/mL were assigned to four groups: Exercise + Vitamin D (Ex + VitD, n = 15), Exercise + Placebo (Ex + Placebo, n = 13), Vitamin D only (VitD, n = 11), or Control (n = 13). Exercise groups completed supervised progressive resistance training three times weekly, and vitamin D groups received 2000 IU/day cholecalciferol. Results: The Ex + VitD group achieved significant improvements in HbA1c (−0.13%, p = 0.019), fasting glucose (−0.79 mmol/L, p < 0.001), insulin (−1.96 μU/mL, p = 0.050), and HOMA-IR (−0.77, p = 0.020). Serum 25(OH)D increased substantially (+15.57 ng/mL, p < 0.001). Calcitonin rose exclusively in the Ex + VitD group (+2.57 pg/mL, p < 0.001, d = 3.34), while monotherapies showed no change. Total cholesterol (−23.93 mg/dL), triglycerides (−25.07 mg/dL), and LDL-cholesterol (−10.20 mg/dL) decreased significantly. Both exercise groups showed marked strength gains (chair stand +8.33 to +10.00 repetitions, p < 0.001) and balance improvements (functional reach +2.47 to +4.46 cm, p ≤ 0.033). Conclusions: Twelve weeks of progressive resistance training combined with vitamin D supplementation produced enhanced combined improvements in glycemic control, insulin sensitivity, calcitonin secretion, muscular strength, and lipid metabolism in elderly women with T2DM and vitamin D deficiency, targeting complementary pathways that neither intervention engaged alone. Full article

Extra virgin olive oil (EVOO) is a hallmark of the Mediterranean diet and an important dietary source of bioactive phenolic compounds, including hydroxytyrosol and tyrosol derivatives, which have been investigated in relation to cardiometabolic health. However, the potential metabolic effects of phenolic-rich EVOO in young healthy adults remain poorly characterized. In this randomized crossover trial, 28 healthy adults (29.0 ± 3.4 years) consumed either phenolic-rich EVOO or regular olive oil (OO) (0.7 g/kg/day) for 4 weeks. The cardiometabolic outcomes reported here were secondary endpoints of the trial. Anthropometric measurements, cardiometabolic biomarkers, and urinary phenolic metabolites were assessed at baseline and after each intervention period; selected phenolic metabolites were quantified in 24-h urine using targeted LC–HRMS. Treatment effects were evaluated using mixed-effects models. Compared with OO, EVOO markedly increased urinary hydroxytyrosol-glucuronide (GMR = 9.9; 95% CI: 2.0, 49.0; p = 0.005), together with other hydroxytyrosol- and tyrosol-derived metabolites, providing objective evidence of greater phenolic exposure during the EVOO intervention. Exploratory between-intervention differences favored EVOO for waist circumference (β = −2.21 cm; 95% CI: −3.37, −1.05), waist-related indices, and HbA1c (β = −0.13%; 95% CI: −0.25, −0.01). In exploratory analyses, increases in urinary hydroxytyrosol-glucuronide during EVOO intake were inversely correlated with changes in HbA1c (Spearman’s rho = −0.49, p = 0.011) and WHR (rho = −0.38, p = 0.048). Post hoc sensitivity analyses showed greater stability for the waist-circumference estimate than for HbA1c. Overall, phenolic-rich ‘Corbella’ EVOO substantially increased urinary phenolic metabolite exposure, whereas the observed cardiometabolic differences should be considered exploratory and hypothesis-generating and require confirmation in larger trials specifically powered for these outcomes. Full article

Introduction: Lifestyle interventions are a fundamental component of type 2 diabetes mellitus management; however, evidence from real-world clinical settings regarding multicomponent interventions that simultaneously evaluate behavioral, metabolic, and anthropometric outcomes remains limited. Objective: To evaluate the effect of a multicomponent lifestyle intervention program on dietary habits, biochemical parameters, physical activity, and anthropometric indicators in adults with type 2 diabetes mellitus in the Peruvian Amazon. Methods: A quasi-experimental study with a non-randomized control group and pre–post assessments was conducted among 144 adults with type 2 diabetes mellitus (72 in the intervention group and 72 in the control group) receiving care at a hospital in the Peruvian Amazon. The three-month intervention included nutrition education sessions, practical workshops, group-based physical activity sessions involving traditional dance and Zumba, home visits, and follow-up through telephone calls and WhatsApp. Dietary habits, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), lipid profile, physical activity (PA), body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) were assessed. Intervention effects were estimated using linear mixed-effects regression models adjusted for age, sex, and disease duration. Results: Compared with the control group, participants receiving the intervention experienced greater improvements in dietary habits (β = 17.85; 95% CI: 16.80 to 18.89; p < 0.001), together with greater reductions in FBG (β = −84.23 mg/dL; 95% CI: −100.45 to −68.01; p < 0.001) and HbA1c (β = −2.32 percentage points; 95% CI: −2.74 to −1.90; p < 0.001). Greater reductions were also observed in triglycerides (β = −53.68 mg/dL), total cholesterol (β = −31.73 mg/dL), BMI (β = −1.67 kg/m²), WC (β = −5.31 cm), and WHtR (β = −0.034) (all p < file0.001). PA increased to a greater extent among participants receiving the intervention (β = 3015.40 MET-min/week; 95% CI: 2769.81 to 3260.99; p < 0.001), whereas no significant between-group difference in change was observed for serum creatinine (p = 0.075). Conclusions: Participation in a three-month multicomponent lifestyle intervention was associated with greater improvements in dietary habits, physical activity, glycemic control, lipid profile, and anthropometric indicators compared with usual care among adults with type 2 diabetes mellitus in the Peruvian Amazon. Full article

Objective: This study aimed to investigate the combined associations of food insecurity and Mediterranean diet adherence with glycemic control and to determine whether gut-derived metabolites differ according to food insecurity and macrovascular complication status in adults with type 2 diabetes mellitus (T2DM). Methods: In this cross-sectional study, food insecurity was assessed using the Food Insecurity Experience Scale, and Mediterranean diet adherence was evaluated with the 14-item Mediterranean Diet Adherence (MDA) Scale. Serum trimethylamine N-oxide (TMAO) and L-carnitine concentrations were quantified using enzyme-linked immunosorbent assay (ELISA). Multinomial logistic regression was used as the primary analysis of data-derived HbA1c tertiles, and separate binary logistic regression models were performed as sensitivity analyses. ANCOVA was used for adjusted comparisons of continuous outcomes. Results: In the primary multinomial analysis, none of the combined food insecurity–MDA patterns were significantly associated with the intermediate or highest HbA1c tertiles after multivariable adjustment. However, point estimates suggested higher odds of the intermediate HbA1c tertile among participants with food insecurity and high MDA adherence (AOR = 3.41, 95% CI: 0.76–15.25) and of the highest HbA1c tertile among those with food insecurity and low MDA adherence (AOR = 4.74, 95% CI: 0.66–34.16); these estimates were imprecise. Sensitivity analyses using separate binary logistic regression models yielded stronger associations, but these findings should also be interpreted cautiously. Participants with macrovascular complications exhibited significantly higher serum TMAO and L-carnitine concentrations (p = 0.026 and p = 0.039, respectively), whereas food-insecure participants had significantly lower concentrations of both metabolites (p = 0.009 and p = 0.018, respectively). Higher dietary fiber and plant protein intakes were cross-sectionally associated with lower TMAO concentrations, while L-carnitine concentrations were positively associated with dietary fiber intake and inversely associated with plant protein intake. Conclusions: Combined food insecurity–MDA patterns showed suggestive but imprecise differences in HbA1c category membership that require confirmation in larger prospective studies. Serum TMAO and L-carnitine concentrations differed according to food insecurity and macrovascular complication status and were associated with selected dietary components. These findings should be interpreted as exploratory cross-sectional associations rather than evidence of causal or mechanistic effects. Full article

Metabolic syndrome (MetS) is a composite classification defined by heterogeneous combinations of cardiometabolic abnormalities. Several components have been associated with pancreatic cancer (PC), but studies often conflate long-term metabolic exposure, tumor-related prediagnostic metabolic change, and prognosis after diagnosis. This review critically evaluates these three settings. This narrative review searched PubMed, Scopus, and Web of Science through April 2026, prioritizing meta-analyses, prospective cohorts, Mendelian randomization studies, clinical studies, preclinical mechanistic evidence, and guidelines. Evidence was interpreted with attention to reverse causation, residual confounding, outcome definitions, and validation. Meta-analyses report a 25–34% higher PC risk among individuals with MetS, with a stepwise gradient across the number of metabolic components; hyperglycemia showed the strongest association among individual components (RR 1.55, 95% CI 1.42–1.70). However, MetS represents multiple versions of exposure, and the epidemiological and clinical evidence remains predominantly observational. Proposed mechanisms involving insulin signaling, adipokines, oxidative stress, epigenetic regulation, and the microbiome are largely preclinical and are not pancreas-specific. New-onset diabetes, rising HbA1c, and involuntary weight loss may mark occult pancreatic ductal adenocarcinoma, but available risk-enrichment models and biomarkers are insufficiently validated for routine screening. After diagnosis, metabolic status and body-composition measures have been associated with survival and perioperative outcomes, although confounding and cancer-related cachexia complicate interpretation. MetS is consistently associated with PC risk but is neither a single causal exposure nor an established target for PC prevention. MetS alone does not justify pancreatic imaging or biomarker testing. Lifestyle and pharmacologic treatment should follow established cardiometabolic indications; their effects on PC incidence remain unproven. Priorities include component-specific causal studies and prospective validation of risk-enrichment strategies. Full article

Background: While nutritional interventions are pivotal for the prevention and management of gestational diabetes mellitus (GDM), the optimal nutritional strategy remains unclear. Methods: PubMed, EMBASE, Cochrane Library and Web of Science were searched for randomized controlled trials (RCTs). Eligible studies targeted both GDM-diagnosed patients and high-risk cohorts, comparing nutritional interventions with standard controls. Data were extracted and synthesized through network meta-analyses to estimate the standardized mean difference (SMD) or relative risk (RR). The primary outcomes were incidence of GDM, fasting blood glucose (FBG), HOMA-IR, glycated hemoglobin (HbA1c), gestational weight gain (GWG), and cesarean section rate (CSR). Results: A total of 59 trials involving 10,262 women evaluated 24 nutritional strategies. Among high-risk pregnant women, inositol was associated with a reduced incidence of GDM (RR = 0.50, 95% CI: 0.37, 0.68; SUCRA = 84.5%) and lower FBG levels (SMD = −0.42, 95% CI: −0.66, −0.18; SUCRA = 89.8%). For CSR in high-risk pregnant women, blueberry combined with dietary fiber showed a favorable ranking (RR = 0.30, 95% CI: 0.10, 0.90; SUCRA = 97.8%). Among patients with GDM, the Dietary Approaches to Stop Hypertension (DASH) diet showed a significant effect on HOMA-IR (SMD = −2.79, 95% CI: −4.49, −1.09; SUCRA = 95.9%). Plant sterols showed a favorable effect on HbA1c levels (SMD = −1.40, 95% CI: −2.00, −0.80; SUCRA = 95.7%). Fish oil was associated with reduced GWG (SMD = −0.44, 95% CI: −0.76, −0.12; SUCRA = 94.1%). Combined supplementation with magnesium, zinc, calcium, and vitamin D ranked favorably for CSR compared with the control group (RR = 0.44, 95% CI: 0.15, 1.29; SUCRA = 82.1%), but this finding was based on limited evidence. Conclusions: Current evidence suggests that inositol, the DASH diet, plant sterols, and fish oil may play a positive role in the prevention and management of gestational diabetes. However, the effects of interventions with very high SUCRA scores but limited supporting evidence—such as blueberries combined with dietary fiber and magnesium–zinc–calcium–vitamin D supplements—should be interpreted with caution. Well-designed, large-scale randomized controlled trials are needed in the future to further confirm these findings. Full article