Background: Diabetes of the exocrine pancreas (DEP) is a form of diabetes that arises in the presence of an exocrine pancreas disease and is mainly associated with acute and chronic pancreatitis. Therapeutic management of DEP has not changed over the past decades, and treatment is mostly insulin based. However, type 2 diabetes (T2D) treatment guidelines have changed with the aim of normalizing glucose levels and preventing diabetes-related comorbidities. Objectives: The aim of this study was to evaluate real-word practice in the treatment of diabetes associated with pancreatitis, with a focus on individuals who had already developed cardiovascular and/or renal diseases. Designs: We conducted a cross-sectional observational study on adult patients admitted to a tertiary-level hospital in Italy between 2018 and 2022 with a prevalent diagnosis of pancreatitis and diabetes. Methods: Disease-related real-world data were collected from Hospital Information Systems using automated data extraction strategies and through the implementation of a patient-centered data repository. A multiple source real-world evidence-based methodology was used to identify patients with diabetes and to investigate changes in glucose-lowering treatments through hospitalizations. Results: We identified 2146 hospitalized patients with pancreatitis from 2018 to 2022, 675 (31.4%) of whom also had diabetes. Data on glucose-lowering therapies were available for 444 of these patients. Individuals with diabetes and pancreatitis were predominantly male (65.2%) and older than those without diabetes ( p < 0.001). At hospital admission, 41.9% were on insulin therapy and 44.4% on other drugs, with metformin being the most prescribed. After hospitalization, insulin use increased significantly (61.2%, p < 0.001) while metformin prescriptions decreased (from 44.7% to 26.2%, p < 0.001). Patients with cardiorenal comorbidities showed similar therapeutic patterns, with a pronounced post-discharge reduction in metformin use. Conclusion: This real-world study provides updated evidence on the treatment of diabetes associated with pancreatitis in a tertiary care setting, showing a predominant use of insulin and metformin regardless of comorbidities. Despite emerging evidence on the benefits of non-insulin therapies in T2D, such approaches are not yet reflected in the management of DEP, underlining the need for specific clinical guidelines and dedicated trials.
Background Insulin resistance is a common metabolic feature of metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D), but its cross-sectional association with the coexistence of these conditions remains incompletely characterized. Objectives To evaluate the associations between the homeostasis model assessment of insulin resistance (HOMA-IR) and the concurrent presence of MASLD and T2D, and to explore potential demographic heterogeneity and generate hypotheses regarding candidate biological pathways. Design Population-based cross-sectional study using data from the National Health and Nutrition Examination Survey 2017–March 2020 pre-pandemic cycle. Methods Adults with fasting glucose, fasting insulin, vibration-controlled transient elastography, and covariate data were included. Participants were classified as having neither condition, MASLD alone, T2D alone, or both. Multivariable logistic regression evaluated HOMA-IR continuously and by quartiles. Interaction and stratified analyses were conducted by sex and race/ethnicity. Secondary analyses examined concurrent MASLD and prediabetes among participants without T2D. Exploratory mediation analyses used fasting serum insulin as the exposure to assess whether glycemic and lipid indicators statistically accounted for part of the association. Network pharmacology was used as a hypothesis-generating approach to predict candidate targets and enriched pathways. Results Among 1,527 participants, each 1-unit increase in HOMA-IR was associated with 59.9% higher odds of concurrent MASLD and T2D versus neither condition (odds ratio [OR] 1.599, 95% confidence interval [CI] 1.491–1.715), 20.2% higher odds versus MASLD alone, and 14.5% higher odds versus T2D alone. When T2D alone was the reference, the association differed by race/ethnicity (P for interaction <0.01). Each 1-unit increase in HOMA-IR was also associated with 22.5% higher odds of concurrent MASLD and prediabetes versus prediabetes alone. Sex-related heterogeneity was observed in secondary comparisons involving concurrent MASLD and prediabetes. The odds of comorbidity were progressively higher across increasing HOMA-IR quartiles (P for trend <0.001). Fasting plasma glucose and hemoglobin A1c statistically accounted for 48.1% and 12.1%, respectively, of the total association between fasting serum insulin and concurrent MASLD and T2D. Hypothesis-generating network pharmacology predicted PRKACA, MAPK1/3, PIK3CA, and SRC as candidate hub targets and suggested candidate pathways related to PI3K-Akt, FOXO, and MAPK signaling. Conclusion Higher HOMA-IR was associated with higher odds of concurrent MASLD and T2D. The magnitude of the associations varied by race/ethnicity and the selected reference group, while sex-related heterogeneity was observed in secondary analyses of concurrent MASLD and prediabetes.
Background Cardiovascular disease (CVD) is more common in those with metabolic dysfunction-associated steatotic liver disease (MASLD). Although the triglyceride-glucose index (TyG) and its composite indices are straightforward indicators of insulin resistance, it is yet unknown how they relate to the risk of CVD in the MASLD population. Objectives To explore the correlation of TyG and TyG-waist-to-height ratio (TyG-WHtR) with cardiovascular disease risk in the MASLD population. Design This was a population-based cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 1999–2023. Methods Adults with MASLD were included using cross-sectional data from the National Health and Nutrition Examination Survey (NHANES). ROC curve assessments, subgroup analyses, smooth curve fitting, and multivariate logistic regression were carried out. Results Among 1,860 participants, TyG (OR=1.27) and TyG-WHtR (OR=1.20) were independently associated with elevated CVD risk after full covariate adjustment (all P <0.05). TyG exhibited a nonlinear association with CVD risk, with an inflection point at 9.28: below this cutoff, higher TyG was strongly linked to greater CVD risk (OR=2.23, 95% CI: 1.56–3.19), whereas no significant association was detected above the threshold. TyG-WHtR also presented a potential inflection point at 5.54. Stratified analyses revealed stronger associations between both indices and CVD among participants without diabetes, and the magnitude of associations varied across racial subgroups. ROC curve analyses indicated that both markers only achieved modest discriminatory performance for identifying prevalent CVD (AUC: 0.606 for TyG; 0.613 for TyG-WHtR). Conclusion TyG and TyG-WHtR showed positive associations with CVD in patients with MASLD, with a remarkable threshold effect observed for TyG. Both indices are simple auxiliary markers to screen high-risk subgroups during population epidemiological surveys.
Background Hypochondroplasia is a skeletal dysplasia characterized by disproportionate short stature that is caused by gain-of-function variants in the fibroblast growth factor receptor 3 gene ( FGFR3 ), which negatively regulates endochondral bone growth. Current treatments are based on symptom management; there are no treatments targeting the signaling pathways that underlie hypochondroplasia. Vosoritide, a C-type natriuretic peptide analog that counteracts overactive FGFR3 signaling to stimulate endochondral bone growth, is approved for the treatment of achondroplasia in children. A phase 1/2 clinical trial demonstrated that vosoritide treatment for 1 year increased growth in children with hypochondroplasia and was well-tolerated. Objectives The objectives of CANOPY HCH-3 are to evaluate the efficacy and safety of vosoritide for the treatment of hypochondroplasia in children. Design CANOPY HCH-3 was a phase 3, randomized, double-blind, placebo-controlled, multicenter study. Methods and Analysis Children aged ≥3 to <18 years with confirmed hypochondroplasia who had ≥6 months of pre-treatment standing height from a prior observational study before randomization were enrolled. Participants were randomized to receive 52 weeks of daily treatment with vosoritide or placebo, followed by 2 weeks of safety follow-up. The primary endpoint is change from baseline in annualized growth velocity at week 52 versus placebo. Ethics CANOPY HCH-3 was conducted in accordance with the Council for International Organizations of Medical Sciences International Ethical Guidelines, the principles of the Declaration of Helsinki and of Good Clinical Practice, and applicable laws and regulations. Protocols were approved by relevant local health authorities, ethics committees, and institutions. Written informed consent from the participant, or parent or legal guardian, was obtained prior to any study-related procedures being performed. Discussion CANOPY HCH-3 will provide further evidence for the efficacy and safety of vosoritide in children with hypochondroplasia.
Iodine is an essential element of human milk. However, high therapeutic maternal doses of potassium iodide (KI) during breastfeeding and its effect on the infant have been insufficiently studied. Therefore, human milk samples were collected within the UmbrelLACT study to determine human milk iodine concentration (HMIC) and estimate infant exposure during and after high maternal KI intake. One mother used KI 3 × 50 mg/day as preparation for thyroidectomy at 5 months postpartum. Human milk samples were collected opportunistically during and within 2 weeks after KI discontinuation. Furthermore, milk samples were collected over 24-h periods at 3 weeks post-discontinuation and monthly from 1 month up to 5 months after discontinuation of KI intake. Breastfeeding was temporarily interrupted during maternal treatment, with partial resumption of breastfeeding 1 week after KI discontinuation, complemented with infant formula upon the participant’s decision. HMIC were analysed using inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) after basic extraction with tetra-methyl ammonium hydroxide (TMAH) and infant exposure was estimated. Median HMIC were 70.8 (46.6–80.8) µg/mL during and 0.064 (0.016–0.227) µg/mL from day six after maternal treatment stop onwards. After discontinuation of KI intake, HMIC decreased quickly and remained within reference range (0.1–0.2 µg/mL). Using the infant requirement of 15 µg/kg/day, relative infant recommended dose (RID recommended ) during and after KI intake was 70805% and 98%, respectively. The infant’s thyroid values were within normal ranges at 3 months after discontinuation of maternal treatment and no adverse events were reported for the infant. Post-discontinuation HMIC are in line with mean concentrations in Nordic countries (68–90 ng/mL). High therapeutic doses of KI should not be combined with breastfeeding, but based on these results (exclusive) breastfeeding could be resumed from 3 weeks after finalisation of maternal treatment. Further research is warranted to determine exposure and safety for breastfed infants. Registration UmbrelLACT study: NCT06042803 ( https://clinicaltrials.gov/study/NCT06042803?cond=umbrellact&rank=1 ).
Patients with adrenal Cushing’s syndrome may also have undiagnosed primary aldosteronism—a condition that causes high blood pressure and low potassium. Both hormone problems can arise from the same adrenal tumor. In a Colombian registry study of 130 patients, none of the 22 with adrenal Cushing’s syndrome were screened for aldosterone excess before surgery. Because high blood pressure and low potassium occur in both conditions, some postoperative problems may be due to unrecognized aldosterone excess rather than cortisol alone. We suggest routine screening for primary aldosteronism in patients with adrenal Cushing’s syndrome who have high blood pressure, as recommended by current guidelines, to enable more accurate diagnosis and personalized treatment.
Background: Cardiovascular disease (CVD) is the leading cause of mortality worldwide. The C-reactive protein–triglyceride–glucose (CTI) index captures metabolic inflammation and insulin resistance, while obesity indices reflect adiposity-related cardiometabolic risk. However, the predictive value of combining CTI with obesity indices for CVD remains unclear. Objectives: To examine the prognostic utility of CTI combined with established and novel obesity indicators for CVD, and to benchmark their predictive efficacy. Design: Nationally representative prospective cohort study. Methods: Using data from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative prospective cohort, 7847 adults aged 45 years and above without baseline CVD were enrolled. CTI was calculated from C-reactive protein, fasting blood glucose, and triglycerides (TG); each obesity index was combined with CTI to form composite parameters (CTI-body mass index (CTI-BMI), CTI-waist circumference (CTI-WC), CTI-waist-to-height ratio (CTI-WHtR), CTI-body roundness index (CTI-BRI), CTI-weight-adjusted waist index (CTI-WWI), CTI-Chinese visceral adiposity index (CTI-CVAI), CTI-a body shape index (CTI-ABSI)). We employed Cox proportional hazard models, restricted cubic spline analyses, Kaplan–Meier survival plots, ROC curve evaluations, and weighted quantile sum (WQS) regression to examine the links and prognostic utility of each metric with incident CVD across baseline and cumulative exposure tiers. Results: Over a 9-year follow-up period, 1938 new-onset CVD cases were documented. Following multivariable adjustment, each CTI-obesity composite metric showed a significant positive link to CVD risk ( p < 0.05). Moreover, all CTI‑obesity composite parameters showed stronger associations with CVD than CTI alone. CTI‑CVAI demonstrated the relatively best predictive accuracy among the evaluated indices, though absolute discriminatory ability remained modest (baseline area under the ROC curve (AUC): 0.596; cumulative AUC: 0.600). Trajectory clustering found that, versus the well-managed group, the poorly managed subgroup had 21%–71% higher CVD risk (max 71% for CTI-WC). WQS regression indicated that CRP and obesity indices (especially CVAI) were the major contributors in the mixed exposure; cumulative exposure WQS analysis showed that cumulative TG and cumulative obesity parameters contributed the most. Conclusion: CTI combined with obesity indices, particularly CTI-CVAI, was associated with modestly improved predictive ability for CVD risk compared with CTI alone. This parameter may offer incremental information for CVD risk stratification by integrating metabolic inflammation and visceral fat markers.
Background: As a critical preclinical stage of type 2 diabetes (T2D), prediabetes necessitates urgent lifestyle interventions to halt disease progression. Despite robust evidence supporting the efficacy of exercise in improving glycemic control, exercise adherence remains suboptimal among individuals with prediabetes. Objectives: This review aimed to identify barriers and facilitators to exercise adherence in individuals with prediabetes while also extracting evidence-based behavior change techniques (BCTs) that may enhance physical activity maintenance. Design: Mixed-methods systematic review Data sources and methods: A comprehensive literature search was performed in 10 databases from inception to November 2024. Guided by the JBI Manual for Evidence Synthesis, a convergent integrated approach was used to map barriers and facilitators to the Behavior Change Wheel (BCW) and Theoretical Domains Framework (TDF). TDF domains were ranked by frequency across studies, while adherence-promoting interventions were mapped to BCW intervention functions and BCTs. Barriers were systematically linked to BCW intervention functions and BCTs to guide implementation design. Results: A total of 36 studies were included, consisting of 9 qualitative studies, 24 quantitative studies (15 randomized controlled trials, 5 cross-sectional studies, and 4 quasi-experimental studies), and 3 mixed-methods studies. The synthesis identified “lack of time,” “lack of appropriate exercise equipment or venues,” and “health-related physical limitations” as predominant barriers. Conversely, “perceived health benefits,” “social support,” and “tools or methods to help with exercise adherence” emerged as key facilitators. These factors were mapped to five primary TDF domains: reinforcement, environmental context and resources, behavioral regulation, social influences, and skills. Furthermore, seven intervention functions derived from the BCW were linked to 21 BCTs. Conclusion: This review highlights multifaceted determinants of exercise adherence in individuals with prediabetes and identifies theory-informed strategies to address barriers to adherence. Determinants supported more consistently across studies may provide a stronger basis for intervention development, whereas less frequently reported findings should be interpreted more cautiously. Trial registration: PROSPERO CRD42024605588.
Background: High body mass index (BMI ⩾25 kg/m 2 ) is a critical driver of the global gout epidemic. We aimed to characterize the evolving burden of gout attributable to high BMI and establish the potential causal links between varying obesity grades and gout risk. Objectives: We aimed to characterize the evolving burden of gout attributable to high BMI and establish the potential causal links between varying obesity grades and gout risk. Design: An observational global epidemiological analysis and a bidirectional two-sample Mendelian randomization (MR) study. Methods: Utilizing Global Burden of Disease (GBD) 2021 data, we analyzed disability-adjusted life years (DALYs) and age-standardized DALY rates across 204 countries. Trends were assessed via Joinpoint regression, decomposition, and inequality analyses. Future trajectories were projected using Bayesian age-period-cohort models. Bidirectional MR evaluated the causal impact of Class 1–3 obesity on gout, adjusting for multiple comparisons. Results: From 1990 to 2021, global DALYs for high BMI-related gout increased 2.26-fold, with a 56.9% rise in age-standardized DALY rates. While High-socio-demographic index (SDI) regions face the highest absolute burden, the fastest growth occurred in low-middle SDI regions, indicating a geographic shift. A significant “age-shift” was observed, with the burden increasingly affecting younger males. Epidemiological changes were the primary drivers. MR analysis provided evidence supporting a potential causal relationship between Class 1 and 3 obesity and gout (all odds ratios > 1), with no evidence of reverse causality. Projections suggest that the global age-standardized DALY rates will reach 7.1 per 100,000 by 2040. Conclusion: The global burden of high BMI-related gout is escalating, driven by epidemiological transitions and rising risks in younger men. Genetic evidence supports weight management as a fundamental preventive pillar. Targeted interventions, particularly in rapidly urbanizing regions, are urgently needed to curb this health threat. Trial registration: Not applicable.
Background: Chronic pancreatitis (CP) progressively destroys pancreatic parenchyma and predisposes patients to pancreatogenic type 3c diabetes mellitus (T3cDM). Objectives: We conducted a systematic review and meta-analysis of cohort studies enrolling adults with clinically and/or instrumentally confirmed CP and no pre-existing diabetes at baseline. Design: Systematic review and meta-analysis of cohort studies. Data sources and methods: Scopus, Web of Science Core Collection, and PubMed were searched from inception to August 2025. Random-effects models estimated pooled incidence of new-onset diabetes and the proportion requiring insulin. Prespecified subgroup analyses were stratified by follow-up duration (<60 months, 60–120 months, >120 months). Meta-regression explored demographic, behavioral, and clinical moderators. Results: Nineteen studies met the inclusion criteria and contributed to the primary meta-analysis of incident diabetes after CP. The pooled incidence of diabetes was 30% (95% CI: 27–34; I ² = 94.8%), with a prediction interval of 15%–49%. Exploratory follow-up-stratified analysis suggested a time-dependent increase: 18% (95% CI: 14–22) at <60 months, 25% (95% CI: 15–35) at 60–120 months, and 44% (95% CI: 24–66) at >120 months ( p for subgroup differences = 0.0184). Among patients who developed diabetes, 59% (95% CI: 46–71; 7 studies; I ² = 91.7%) required insulin therapy. Meta-regression did not identify statistically significant study-level moderators, although pancreatic calcification showed a non-significant positive trend. Conclusion: CP is associated with a substantial and time-dependent incidence of diabetes; however, the pooled estimates should be interpreted cautiously because the included studies were observational and highly heterogeneous. These findings support long-term glycemic monitoring and careful classification of pancreatogenic diabetes in patients with CP, while optimal screening intervals and treatment timing require further prospective evidence. Trial registration: PROSPERO CRD420251136931.
Background: Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes requiring timely insulin administration and dynamic fluid/electrolyte management. Objectives: The aim of this study is to assess the effectiveness of an electronic order set (PowerPlan) on time to DKA resolution compared to individual order prescribing. Design: Retrospective cohort study. Methods: This study included patients (⩾14 years old) with DKA, identified via electronic medical records, and matched to pre- and post-PowerPlan groups. The primary outcome was time to DKA resolution. Secondary outcomes included hospital length of stay, appropriateness of initial intravenous fluids, and insulin infusion. Safety outcomes included the number of hypoglycemia, hyperkalemia, and hypokalemia events until DKA resolution. Results: Of 226 matched patients (113 per group), baseline characteristics were comparable. The post-implementation group achieved faster DKA resolution (median 10.6 vs 12.6 h; p = 0.002), higher adherence to fluid and insulin protocols, and shorter hospital stay (3.15 vs 3.61 days; p = 0.04). Safety outcomes were similar, with fewer hypoglycemic events and comparable electrolyte abnormalities. Conclusion: Implementation of the DKA PowerPlan significantly shortened time to resolution and reduced hospital stay without compromising safety. These findings support standardized electronic order sets to enhance efficiency and quality of DKA management.
Automated insulin delivery (AID) is the gold standard of treatment for type 1 diabetes mellitus (T1DM). However, little data on the use in people on peritoneal dialysis (PD) exist. To share real-world experience on the use of AID (Medtronic MiniMed 780G SmartGuard and Guardian 4 continuous glucose monitoring system) in a woman living with type 1 diabetes on PD, we report the implementation despite the complex setting of type 1 diabetes with multiple diabetes-associated complications, PD, visual impairment, and a complete language barrier. Glycemic control 14 days before the start of AID on multiple daily injections and 9 months after the conversion is presented. AID might be a safe and promising therapeutic option for individuals with T1DM and end-stage kidney disease requiring PD. Further research is needed to demonstrate both safety and efficacy in this special population, and assessment of patient-reported outcome measures.
Background: The pathogenesis of diabetes is affected by a complex interplay between numerous environmental and genetic factors. While single-nucleotide polymorphisms (SNPs) are not directly used as biomarkers of the disease, they can be considered an important guide for determining predisposition. Objective: To investigate the roles of raftlin, malondialdehyde (MDA), superoxide dismutase (SOD), and the vitamin D receptor (VDR) BsmI (rs1544410 A>G) polymorphism, in the clinical progression of type 2 diabetes mellitus (T2DM). Design: A retrospective observational case–control study. Methods: A total of 300 subjects were included in the study: 104 with T2DM, 85 with prediabetes, and 111 healthy controls. The VDR BsmI polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, while serum MDA, SOD, and raftlin were analyzed via the enzyme-linked immunosorbent assay (ELISA) method. Results: No statistically significant differences were observed in the allelic and genotype frequencies of the VDR gene BsmI polymorphism between T2DM prediabetes patients and controls ( p = 0.97, p = 0.58, respectively). MDA levels were higher, while raftlin levels were lower in patients with T2DM and prediabetes compared to controls ( p < 0.05). Within the T2DM cohort, HbA1c ( p = 0.014), MDA ( p = 0.001), and raftlin ( p < 0.001) differed significantly between the BB and bb genotypes, with a positive correlation between the bb genotype and HbA1c ( p = 0.008, r = 0.287). Receiver operating characteristic (ROC) analysis revealed raftlin’s diagnostic potential among T2DM patients with the BB and bb genotypes, with an area under the curve (AUC) of 0.839, a specificity of 69.2%, and a sensitivity of 81.5%. Conclusion: To the best of our knowledge, this is the first study to demonstrate that raftlin exhibits significant diagnostic efficacy in individuals with the bb genotype within a clinical T2DM cohort.
What is this summary about? Obesity is a complex, long-term condition that affects far more than a person's physical health. It can impact emotional well-being (how happy a person feels), mental health (how a person feels about daily life), relationships, and quality of life. In a study of 7,000 people across a range of body sizes, researchers found that people living with obesity reported lower self-esteem (lower satisfaction with oneself), higher levels of depression (feeling sad or hopeless) and stress, and greater feelings of loneliness compared with those not living with obesity. Many also shared that they received less empathy (less understanding) and faced more stigma (judgment). These findings highlight the need for well-rounded care that focuses on empathy in all areas of well-being for people living with obesity. What is the purpose of this plain language summary? The number of people worldwide living with excess weight or obesity (people who weigh more than what is considered healthy) has increased in recent decades. Researchers in this study asked people living with obesity about their wellbeing. People interviewed in this study also shared their experiences with judgment (stigma) or understanding about their obesity. This study shows how greatly weight-related stigma can impact the well-being of people living with obesity.
Background:Congenital persistent hyperinsulinemic hypoglycemia (HH) is a rare disorder that can lead to severe and recurrent hypoglycemic episodes in neonates and infants. Management often requires intensive glucose infusion via central venous catheters (CVCs), which may increase the risk of thrombosis. While case reports suggest thrombosis can occur in HH, the incidence, risk factors, severity, and outcomes remain poorly understood. Objectives:This study aimed to determine the incidence of thrombosis in children with persistent HH and to evaluate potential risk factors associated with thrombotic complications. Design:A descriptive, retrospective cohort study of patients with persistent HH followed at a university pediatric endocrinology clinic between January 2000 and December 2025. Methods:Twenty patients with persistent HH were included. Data on demographics, clinical characteristics, laboratory results, treatment protocols, CVC use, timing and location of thrombosis were collected. Patients who developed thrombosis were compared with those who did not to identify risk factors. Results:Among 20 patients, 55% were male, with a median age at diagnosis of 1 day. A total of 23 CVCs were placed in 15 patients, with a median dwell time of 38 days. Thrombosis occurred in nine patients (45%), including six catheter-related and three catheter-independent intracranial thrombosis. Median age at thrombosis detection was 74 days. Patients who developed thrombosis experienced significantly more hypoglycemic episodes and more days with hypoglycemia (p < 0.05). No association was found between genetic mutations (ABCC8, KCNJ11, etc.) and thrombosis development. All four patients treated with enoxaparin achieved complete resolution without complications. Conclusion:Thrombosis is a frequent and clinically significant complication in persistent HH. Recurrent and severe hypoglycemic episodes are major risk factors. Routine thrombosis screening, particularly in patients with CVCs, may allow early detection and treatment even in asymptomatic cases.
Background: Overactive bladder (OAB) is a common condition that affects both men and women, but its relationship with central obesity and the dietary intake has not been adequately elucidated. Objectives: Our study aims to investigate associations between central obesity replacement indices, dietary intake of sugar and lipids, and OAB risk using National Health and Nutrition Examination Survey 2005–2016 data. Design: Cross-sectional study. Methods: This study analyzed 24,675 adults (4848 OAB cases). Weight, body mass index, and other central obesity replacement indices (waist circumference, weight-adjusted waist index, waist-to-height ratio (WHtR), body roundness index (BRI)) and dietary nutrients intake (carbohydrate, sugars, fat, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids (PUFAs), and cholesterol) were assessed. Propensity score matching (1:2) balanced covariates. Multivariable logistic regression and generalized additive models evaluated dose-response relationships. Results: All central obesity indices showed significant positive associations with OAB ( p < 0.001), with WHtR and BRI demonstrating the strongest effects (adjusted odds ratio (OR) = 2.04, 95% confidence interval: 1.80–2.30). Nonlinear relationships were observed, particularly for WHtR (degrees of freedom = 3.30–6.16). Dietary analysis revealed that OAB patients had significantly higher consumption of total energy, carbohydrates, and sugars (all p < 0.05), and higher sugar intake increased OAB risk (OR = 1.32, p = 0.0016), while PUFAs were protective (OR = 0.79, p = 0.0159). Conclusion: Central obesity replacement indices, especially WHtR and BRI, strongly predict OAB risk. Dietary modifications, including reducing sugars and increasing PUFAs intake, may complement abdominal fat reduction for OAB prevention. These findings highlight the importance of combined weight management and dietary modifications for OAB prevention in high-risk populations.
Background:Comparative evidence on 24-month clinical outcomes and biomarker trajectories with semaglutide, empagliflozin, and sitagliptin in adults with type 2 diabetes (T2D) and obesity remains limited. Objectives:To compare 24-month clinical outcomes and longitudinal biomarker trajectories among semaglutide, empagliflozin, and sitagliptin in people with T2D and obesity. Design:Multicenter retrospective cohort study. Methods:Using TriNetX, we performed an active-comparator, new-user study with three prespecified 1:1 propensity score-matched contrasts: semaglutide versus empagliflozin, semaglutide versus sitagliptin, and empagliflozin versus sitagliptin. Follow-up was intention-to-treat for 24 months. Multiplicity was addressed with Benjamini-Hochberg false discovery rate correction within two prespecified families: (i) clinical time-to-event endpoints (all-cause mortality, MACE, heart failure, MAKE, MALO, atrial fibrillation, stroke) within each comparator pairing, and (ii) window-level laboratory contrasts within each biomarker at baseline, 6, 12, and 24 months. Results:Versus empagliflozin, semaglutide was associated with lower all-cause mortality (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.51-0.69), major adverse cardiovascular events (MACE; HR 0.76, 95% CI 0.66-0.88), and heart failure (HR 0.62, 95% CI 0.54-0.70). Versus sitagliptin, semaglutide was associated with lower all-cause mortality (HR 0.34, 95% CI 0.27-0.42), MACE (HR 0.64, 95% CI 0.51-0.81), and heart failure (HR 0.54, 95% CI 0.43-0.67). Empagliflozin versus sitagliptin showed lower all-cause mortality (HR 0.48, 95% CI 0.40-0.58) and MACE (HR 0.74, 95% CI 0.59-0.92), whereas heart failure did not differ significantly. Conclusion:In matched cohorts with T2D and obesity, semaglutide was associated with lower 24-month mortality and heart failure risk than empagliflozin, and both semaglutide and empagliflozin were associated with lower mortality and MACE than sitagliptin. Trial registration:Not applicable (retrospective cohort); Institutional Review Board approval CS2-24004, Chung Shan Medical University Hospital.
Background:Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used across the glycemic spectrum, yet their thyroid safety profile remains debated. Prior studies have shown inconsistent findings, and evidence across prediabetes, type 1 diabetes (T1D), and type 2 diabetes (T2D) is lacking. Objectives:To evaluate diabetes-type-specific associations between GLP-1RA therapy and thyroid outcomes, including thyroid dysfunction, autoimmune thyroiditis, nontoxic goiter, and thyroid cancer. Design:A real-world, retrospective target-trial emulation using electronic health records (EHR) from a large multicenter network. Methods:We used the TriNetX US Collaborative Network to identify adults with prediabetes, T1D, or T2D initiating GLP-1RAs. Active comparators included usual care and sodium-glucose cotransporter two inhibitors (SGLT2i). Propensity score matching with extensive covariate adjustment was applied. Participants were followed for incident thyroid outcomes for up to 5 years. Sensitivity and subgroup analyses were conducted to assess robustness. Results:Across glycemic states, GLP-1RA therapy demonstrated distinct thyroid safety patterns. In prediabetes and T1D, GLP-1RA use was associated with reduced risks of thyroid dysfunction and all-cause mortality, suggesting potential metabolic or immunomodulatory benefits. By contrast, among individuals with T2D, GLP-1RA exposure was linked to modest increases in autoimmune thyroiditis and nontoxic goiter, particularly among those with obesity or without hypertension. Importantly, no increased risk of thyroid cancer was observed in any glycemic state, providing reassuring evidence regarding long-term endocrine safety. Conclusion:In this large-scale target-trial emulation, GLP-1RAs showed favorable thyroid safety profiles in prediabetes and T1D, while modestly increasing selected nonmalignant thyroid outcomes in T2D. The absence of elevated thyroid cancer risk across glycemic states supports the overall endocrine safety of GLP-1RAs. These findings highlight the importance of individualized monitoring, particularly in metabolically high-risk T2D populations.
Background: Prediabetes comprises three heterogeneous glucometabolic phenotypes and is associated with an increased risk of metabolic dysfunction-associated fatty liver disease (MAFLD). However, the association of different prediabetes phenotypes with the presence of MAFLD and liver fibrosis remains underexplored. Objectives: To examine the association of different prediabetes phenotypes with MAFLD and liver fibrosis. Design: Population-based cross-sectional study. Methods: Prediabetes was stratified as an isolated defect (impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or impaired hemoglobin A1c (IA1c)), two defects (IFG + IGT, IFG + IA1c, or IGT + IA1c), or all three defects (IFG + IGT + IA1c). Hepatic steatosis and liver fibrosis were assessed by vibration-controlled transient elastography. Multivariate logistic regression analysis was conducted to estimate the odds ratio (OR) and 95% confidence interval (CI) for different prediabetes phenotypes associated with MAFLD and liver fibrosis. Results: A total of 1599 subjects (394 with normal glucose tolerance (NGT) and 1205 with prediabetes) were included. The prevalence of MAFLD and liver fibrosis was higher in prediabetes than in NGT. The odds of MAFLD in prediabetes with two or three glucometabolic defects were increased compared with those with a single glucometabolic defect, with insulin resistance as a possible mediator. Compared with isolated IA1c, isolated IGT had an increased prevalence of MAFLD ( p < 0.05). Moreover, glucose-defined prediabetes had higher odds of MAFLD than HbA1c-defined prediabetes (OR 1.72, 95% CI 1.00–2.96). However, there was no significant difference in the odds of liver fibrosis across different prediabetes phenotypes ( p = 0.58). Conclusion: The odds of MAFLD but not liver fibrosis were increased with the increasing number of glucometabolic defects in participants with prediabetes. Trial registration: Not applicable.
