Background: Physical performance provides valuable insights into metabolic and cardiovascular health, particularly regarding metabolic dysfunction-associated steatotic liver disease (MASLD) and coronary artery disease (CAD). Objective: This study examined the relationship between longitudinal changes in physical performance, assessed using the Timed Up and Go (TUG) test, and indicators of MASLD, CAD, and body fat distribution over time. Methods: This 3-year longitudinal prospective cohort study included 1,096 older adults. Participants underwent baseline and follow-up assessments. Based on TUG results, participants were categorized into four groups: Normal→Normal (Group 1), Impaired→Normal (Group 2), Normal→Impaired (Group 3), and Impaired→Impaired (Group 4). MASLD indicators (Fibrosis-4 index [FIB-4], MASLD liver fat score, and hepatic steatosis index [HSI]), CAD indicators (coronary artery calcium [CAC] and coronary artery volume [CAV] scores), and body fat distribution (L3 cross-sectional visceral fat area [L3VFA], L3 cross-sectional subcutaneous fat area [L3SFA], and visceral-to-subcutaneous fat ratio [VSR]) were also analyzed. Results: At baseline, groups with impaired TUG exhibited worse MASLD, CAD, and fat distribution profiles. Longitudinally, within-group analyses revealed distinct trajectories based on TUG changes over 3 years. For MASLD, the FIB-4 index significantly increased in participants whose TUG declined from normal to impaired (Group 3) or remained persistently impaired (Group 4)(p<0.05). For CAD, CAC and CAV scores increased significantly across all four groups (p<0.001). Regarding fat distribution, subcutaneous fat (L3SFA) significantly increased in Groups 3 and 4. Additionally, the proportion of individuals with high visceral fat (VFA ≥160 cm²) increased in these impaired groups, whereas it decreased in those who maintained or improved to a normal TUG (Groups 1 and 2). Conclusion: Baseline TUG impairment and within-group longitudinal TUG deterioration were associated with adverse MASLD, CAD, and fat distribution profiles. While causal relationships cannot be established, TUG performance may serve as a functional marker reflecting metabolic and cardiovascular health status in older adults.
Purpose Various predictors of overall mortality like hypopituitarism and treatment have been demonstrated in pituitary adenomas. Whether these predictors are specific to tumor subtype was not studied. We aimed to directly compare predictors of mortality in clinically significant pituitary adenoma subtypes (acromegaly, Cushing's disease, macroprolactinomas and non-functioning pituitary macroadenomas). Methods We retrospectively analyzed all patients with acromegaly ( n =224), Cushing's disease ( n =42), macroprolactinoma ( n =123) and non-functioning pituitary macroadenomas ( n =310) admitted in our department between 2011 and 2025. The following variables were retrieved: sex, age and maximum tumor diameter at diagnosis, hypopituitarism and radiotherapy. Results Age and tumor size at diagnosis and rates of hypopituitarism and radiotherapy varied considerably between 38 and 57 years (macroprolactinomas vs. non-functioning pituitary macroadenomas), 7 and 25 mm (Cushing's disease vs. macroprolactinomas), 25 and 47% (acromegaly vs. non-functioning pituitary macroadenomas) and 6 and 38% (macroprolactinomas vs Cushing's disease), respectively. Univariate analysis showed that age at diagnosis was positively associated with mortality in all pituitary adenoma subtypes while hypopituitarism was both negatively (hazard ratio=0.37, acromegaly) and positively (hazard ratio=2.71, non-functioning pituitary macroadenomas) correlated with mortality. In multivariate analysis, age at diagnosis remained a consistent predictor (hazard ratio between 1.07 and 1.11) of overall mortality across the entire cohort. Cushing's disease was significantly associated with mortality while hypopituitarism predicted mortality only in non-functioning pituitary macroadenomas (hazard ratio=2.71). Sex, tumor size at diagnosis and radiotherapy were not associated with mortality. Conclusion We confirmed that age is the main predictor of mortality in pituitary adenomas with a similar hazard ratio across all subtypes. Hypopituitarism was associated with an increased mortality only in those with non-functioning macroadenomas.
Background Transgenic mice expressing the C414A-mutant cryptochrome 1 (CRY1 C414A) develop diabetes with progressive beta-cell senescence and the formation of mucinous intra-islet ductal lesions. These lesions exhibit features resembling metaplasia; however, their molecular basis and the potential involvement of endocrine cells remain unclear. This study aimed to define the metaplasia-like program in intra-islet ducts and to characterize endocrine cell phenotypes in this context. Methods Gene expression microarrays were analyzed using islets from aged CRY1 C414A transgenic and wild-type mice. Histological analyses included Alcian blue staining, lectin labeling, and immunostaining for markers of mucin production, metaplasia, and endocrine differentiation. Marker expression in intra-islet ductal lesions was evaluated to assess their progression and cellular composition. Results Transgenic islets exhibited upregulated expression of metaplasia-associated genes, including mucin 6, trefoil factor 2, and gastrokine 3. Intra-islet ducts, particularly smaller lesions, showed strong mucin production and co-expression of metaplasia-related markers. Tuft cell-associated markers were detected in both intra-islet lesions and pancreatic duct glands. In addition, subsets of insulin-positive cells adjacent to lesions exhibited reduced insulin granularity and expression of metaplasia markers, while glucagon-positive cells were prominent in early lesions. Conclusion Intra-islet ductal lesion formation in CRY1 C414A transgenic mice is associated with activation of a pyloric/spasmolytic polypeptide-expressing metaplasia-like metaplastic program and endocrine cell plasticity. These findings provide a framework linking intra-islet duct formation to established metaplastic processes and suggest a potential relationship beta-cell dedifferentiation and broader endocrine cell plasticity under chronic islet stress.
Aim Insulin resistance is a central pathological feature underlying various metabolic disorders, involving complex mechanisms and multi-organ dysfunction. This study investigates the role of the acute-phase protein orosomucoid in systemic glucose homeostasis. Methods This study utilized high-fat diet-induced obese mice to model insulin resistance. The genetic deletion of orosomucoid 1 was applied, and the metabolic effects of exogenous orosomucoid administration were examined. Molecular analysis included assessing protein kinase B phosphorylation. The dependency of observed benefits on specific receptors was tested using pharmacological inhibition of C-C chemokine receptor type 5 and evaluation of the leptin receptor's role. Results We demonstrate that genetic deletion of orosomucoid 1 induces insulin resistance, whereas exogenous orosomucoid administration improves glucose tolerance and insulin sensitivity in high-fat diet mice. At the molecular level, orosomucoid augments insulin-induced protein kinase B phosphorylation. Notably, these metabolic benefits are independent of the leptin receptor but are critically dependent on the C-C chemokine receptor type 5, as demonstrated by pharmacological inhibition. Conclusion Our findings establish orosomucoid as an endogenous insulin sensitizer via the C-C chemokine receptor type 5/protein kinase B pathway, coordinately ameliorating insulin resistance across multiple metabolic organs and highlighting its therapeutic potential as a novel target for metabolic disorders.
Objective Mild autonomous cortisol secretion is the most prevalent hormonal disorder identified in adrenal incidentalomas. Previous studies suggest a potential correlation between adrenal adenoma size and cortisol secretion. The aim of this study was to evaluate the associations of maximum adenoma diameter and adenoma volume with 24-hour urinary free cortisol levels and post-1-mg dexamethasone suppression test cortisol levels in patients with mild autonomous cortisol secretion. Subjects and methods This cross-sectional observational study included 48 patients aged 18-65 years diagnosed with mild autonomous cortisol secretion. Mild autonomous cortisol secretion is defined as a serum cortisol level of >= 1.8 & micro;g/dL after the 1-mg dexamethasone suppression test and a low morning adrenocorticotropic hormone. The 24-hour urinary free cortisol level was measured using liquid chromatography-tandem mass spectrometry. A radiologist blinded to hormonal test results assessed the maximum adenoma diameter and adenoma volume. Results The study population comprised 48 patients (women/men=43/5) with a mean age of 56.79 +/- 8.81 years. The mean maximum adenoma diameter and adenoma volume were 31.39 +/- 9.43 mm and 10.00 +/- 7.71 cm 3 , respectively. The mean 24-hour urinary free cortisol level was 25.34 +/- 18.21 & micro;g/24 h. The 24-hour urinary free cortisol levels were positively correlated with both the maximum adenoma diameter and adenoma volume ( rho =0.518, p <0.001 and rho =0.520, p <0.001, respectively), whereas no significant correlations were observed between post-1-mg dexamethasone suppression test cortisol levels and either the maximum adenoma diameter or adenoma volume. Conclusion In patients with mild autonomous cortisol secretion, 24-hour urinary free cortisol levels were positively associated with maximum adenoma diameter and adenoma volume, whereas no significant associations were observed for post-1-mg dexamethasone suppression test cortisol levels. The clinical significance of these cross-sectional associations requires further investigation in large prospective longitudinal studies.
