Diabetes mellitus (DM) is a major risk factor for acute myocardial infarction (AMI) and is associated with increased mortality. Despite substantial advances in the management of both conditions, the population-level mortality burden involving AMI as the underlying cause and DM as a contributing cause remains insufficiently characterized. This study aimed to evaluate national trends and disparities in mortality involving AMI as the underlying cause and DM as a contributing cause among U.S. adults aged ≥ 25 years from 1999 to 2025 using CDC WONDER data, forecasts were generated through 2030, with exploratory projections extending through 2040, stratified by DM type, age, sex, and race and ethnicity. A retrospective analysis of U.S. national mortality data from 1999 to 2025 was conducted to identify deaths among adults aged ≥ 25 years in which AMI; ICD-10 code I21 was the underlying cause and DM; ICD-10 codes E10–E14 was a contributing cause. Age-adjusted mortality rates (AAMRs) and crude mortality rates (CMRs) were calculated. Temporal trends were assessed using joinpoint regression to estimate annual percent changes (APCs) and average annual percent changes (AAPCs). Time-series methods were used to forecast mortality through 2030, with exploratory projections through 2040 . Trend analyses were conducted using observed mortality data from 1999 to 2025, whereas projections extended from 2026 to 2040. A total of 762,802 deaths were attributed to AMI, with DM documented as a contributing cause, among U.S. adults aged ≥ 25 years from 1999 to 2025. Overall mortality significantly declined (AAMR: 18.9 to 9.16; AAPC: -3.05; 95
Hereditary pheochromocytoma and paraganglioma (PPGL) are rare, genetically determined neuroendocrine tumors that often present at a young age. Their multifocal nature poses diagnostic and therapeutic challenges and warrants early genetic testing. A 26-year-old man was referred for cervical and mediastinal paragangliomas. Computed tomography scan revealed multiple cervical and mediastinal paragangliomas and bilateral pheochromocytoma. Plasma normetanephrine was 2616 ng/L (13 times the upper normal limit). Genetic testing confirmed an SDHD mutation. After alpha- and beta-blockade, the patient underwent bilateral adrenalectomy and mediastinal paraganglioma resection under cardiopulmonary bypass. Octreotide therapy was initiated due to inoperability of cervical paragangliomas.However, a loss of therapeutic response was observed one year after the initiation of somatostatin analogue. Radiotherapy was then considered for the cervical paragangliomas. This case underlines the complexity of PPGL management in patients with SDHD mutation. Multifocal disease demands individualized, multidisciplinary strategies and long-term follow-up to minimize morbidity and optimize outcomes in young patients.
Type 2 diabetes mellitus (T2DM) is interconnected disturbances in insulin signaling, pancreatic β-cell function, redox and inflammatory homeostasis, lipid metabolism, mitochondrial function, and signaling mediated by advanced glycation end-product (AGE) and their receptors (RAGE). Although available antidiabetic therapies provide substantial clinical benefit, progressive β-cell dysfunction, and diabetes-associated tissue injury remain important clinical challenges. Ursolic acid (UA), a naturally occurring pentacyclic triterpenoid, has demonstrated broad preclinical metabolic and organ-protective effects, but the supporting evidence remains fragmented across individual pathways and experimental models. This review provides as updated, T2DM focussed in vitro, animal and limited human evidence, integrating UA-specific findings across insulin receptor/PTP1B signaling, β-cell preservation, redox regulation, inflammation, lipid metabolism, mitochondrial homeostasis and AGE-RAGE-associated injury. A key contribution is to stratify the mechanistic evidence rather than treating all pathway associations as equivalent, distinguishing direct or intervention-supported findings from expression-level associations, computational predictions and effects that may occur secondarily to improvements in glycaemia, insulin sensitivity, adiposity or oxidative stress. The review focus is comparatively stronger for the insulin-sensitising, lipid-regulatory, antioxidant and anti-inflammatory effects of UA, whereas direct AGE–RAGE modulation, circadian regulation and some pathway specific β-cell mechanisms remain preliminary. The translational development of UA is constrained by poor aqueous solubility, low oral bioavailability, uncertain dose exposure relationships, limited dose standardisation, insufficient long-term safety data, and lack of robust clinical validation in patients with T2DM. UA represents a multi-target preclinical candidate, rather than a clinically established antidiabetic therapy. Future research should prioritise pathway-specific validation, standardized diabetes-relevant models, pharmacokinetic pharmacodynamic correlation, controlled clinical studies, and long-term safety assessment.
Obesity poses significant challenges for those seeking long-term weight loss through diet and exercise alone. Semaglutide is a GLP-1 receptor agonist approved for chronic weight management in eligible adults. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of semaglutide for treating obesity in adults without diabetes. The protocol was registered in PROSPERO (CRD420261338170). PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched through February 28, 2026. We included randomized controlled trials (RCTs) comparing semaglutide with placebo in adults without diabetes with BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 and at least one obesity-related comorbidity. The Cochrane Risk of Bias 2 Tool, GRADE methodology, RevMan v5.4, and CMA v3 were used for risk-of-bias assessment, certainty-of-evidence assessment, data analyses, and meta-regression analyses respectively. We included 10 RCTs with a total of 7,131 participants. Risk-of-bias was judged at the level of each outcome: all included trials were at low risk-of-bias for the efficacy outcomes and the prespecified safety outcomes, while cardiovascular and psychiatric disorders raised some concerns. Compared to placebo, semaglutide produced significantly greater reductions in percentage change in body weight (WMD -12.29
Premature atherosclerotic cardiovascular disease (ASCVD) is associated with a substantial burden of modifiable cardiovascular risk factors, but the dietary and cardiometabolic characteristics of affected patients remain insufficiently characterized. This study aimed to assess Mediterranean diet adherence, its associated factors, and the sex-specific distribution of cardiometabolic risk factors among patients with premature ASCVD in Iran. In this cross-sectional study, 425 adults with premature ASCVD were recruited from a tertiary cardiovascular referral center in Alborz Province, Iran, using consecutive sampling on two scheduled data-collection days per week. Sociodemographic, lifestyle, anthropometric, and biochemical data were collected using standardized protocols. Mediterranean diet adherence was assessed using a culturally adapted 13-item Mediterranean Diet Adherence Screener (MEDAS). Principal component analysis was used to derive dietary adherence patterns from the MEDAS components, and the standardized score of the first principal component was dichotomized at its sample median (0.33) into lower- and higher-adherence groups. Cardiometabolic risk factors were defined according to established clinical criteria, with treated hypertension, diabetes, and dyslipidemia also identified based on relevant medication use. Sex-specific comparisons and multivariable logistic regression were performed. A sensitivity analysis compared participants with extremely premature ASCVD (< 40 years) with those with premature ASCVD (≥ 40 years). Among the 425 participants, 70.1
