搜索结果：Minerva endocrinology

暂无摘要（点击查看详情）

Sarcopenic obesity is closely related to metabolic dysfunction-associated steatotic liver disease (MASLD), but the independent contributions of lean mass and fat mass components to MASLD are not well understood. Our study aimed to evaluate the relationship between the dual-energy X-ray absorptiometry (DXA)-derived soft tissue components and the extent of liver steatosis in patients with MASLD. A cross-sectional study of 118 obese/overweight patients aged 33-78 years, with type 2 diabetes mellitus (T2DM) or prediabetes and MASLD, on oral antidiabetic medication was conducted. Sex-stratified correlation analysis was performed between DXA-derived lean mass and fat mass parameters, (e.g., relative muscle mass [RMM], lean mass/ fat mass [LM/FM] and appendicular lean mass [ALM]), as well as between each of those parameters and the hepatic steatosis index (HSI). Multiple linear regression models were fitted with android fat percentage as the dependent variable, and lean mass indices as independent variables. The models were adjusted for age, sex, the HOMA index, triglyceride and ALT levels. Accordingly, ROC curves were plotted with HSI=36 as a classifier of steatosis. A significant negative correlation was detected between android fat % and RMM (r=-0,96, P≤0.001), between android fat percentage and ALM /BMI (r=-0.70, P≤0.001), between android fat percentage and ALM /height2 (r=-0.28, P≤0.001); between HSI and RMM (r=-0.50, P≤0.001); and between HSI and ALM/BMI (r=-0.39, P≤0.001). The significant positive correlations were as follows: android fat percentage and BMI (r=0.53, P≤0.001); android fat % and ALT (r=0.25, P=0.04); HSI and android fat percentage (r=0.59, P≤0.001); HSI and gynoid fat % (r=0.39, P≤0.001). The AUCs for android fat percentage in the models calculated from LM/FM were as follows: adjusted for the HOMA index, age and sex group, ROC=0.748 (95% CI 0.66-0.83); adjusted for ALT and sex group, ROC=0.743 (95% CI 0.66-0.83). The AUC for android fat percentage in the model calculated from RMM: adjusted for triglycerides, ALT and sex group, ROC=0.741 (95% CI 0.65-0.83). Our findings demonstrate that an increase in android fat distribution and a decrease in lean mass are positively associated with MASLD. The regression models support the utility of DXA-derived indices as practical, indirect markers of liver steatosis for clinical application in patients with TDM2 and MASLD.

Premature ovarian insufficiency (POI) is a critical condition affecting young women before the median age of menopause and consisting of spontaneous oligo-amenorrhea for at least four months associated with follicle stimulating hormone (FSH) levels ≥25 UI/L detected before 40 years of age. Several causes like genetic abnormalities, autoimmune diseases, drugs and/or pelvic surgery may favor this condition that is associated with a deeper clinical impact on women's health compared to physiological menopause. Specifically, cardiovascular and musculoskeletal systems as well as brain could be especially affected by the early loss of ovarian hormones. Therefore, appropriate treatment is necessary to adequately narrow the biological gap with the average age of menopause. Hormone replacement therapy (HRT) is the treatment of choice, regardless of the presence of neurovegetative symptoms. Transdermal high dosage of natural estradiol is generally preferred to guarantee the preservation of cardio-metabolic and bone health. When contraception is required, oral estroprogestins (EPs) maybe considered. A referral to reproductive experts for fertility preservation techniques should be considered case by case.

Papillary thyroid carcinoma (PTC) has classically been considered a sporadic carcinoma. However, a subgroup with familial clustering has been observed, which appears to present a poorer prognosis than the sporadic form. The aim of this study is to analyze the recurrence rates and prognostic factors for familial PTC (FPTC) treated with curative intent. Multicenter national study, endorsed by the Spanish Association of Surgeons. Study population: patients with FPTC (families who have at least 2 first-degree relatives with a confirmed PTC) who meet cure criteria after the treatment. Study endpoints: recurrence rate and risk factors for recurrence. Statistical analysis: Cox regression analysis and survival analysis. The study included 252 cases with a mean follow-up of 90±68,9 months, recurrence in 26.9% (N.=68) and a disease-free survival of 183,46±7,8 months. In the multivariate analysis, the independent factors for the risk of recurrence were: 1) the number of patients with FPTC in the family (OR 1.165); 2) the multifocality (OR 2.525); 3) the vascular invasion (OR 2.770); and 4) TNM staging system (OR 5.128). In the reanalysis that included the American Thyroid Association (ATA) risk of recurrence, this variable was highly predictive of recurrence (OR 12.048). FPTC presents a high recurrence rate, which is related to the number of cases of FPTC in the family, the presence of multifocality and vascular invasion, the TNM staging system and the ATA recurrence risk assessment.

Obesity has reached epidemic proportions globally, with its prevalence nearly tripling since 1975. It is now recognized as a chronic, relapsing disease associated with increased morbidity and mortality due to its strong relationship with several cardio-renal-metabolic conditions. This narrative review aims to explore the major obesity-related complications - namely obstructive sleep apnea syndrome (OSAS), metabolic dysfunction-associated steatotic liver disease (MASLD), dyslipidemia, and chronic kidney disease (CKD) - highlighting their pathophysiological mechanisms, clinical consequences, and current therapeutic strategies. Obesity contributes to OSAS by increasing upper airway collapsibility and to MASLD through ectopic fat accumulation, insulin resistance, and inflammatory responses. Dyslipidemia in obesity is characterized by elevated triglycerides, small dense LDL particles, and low HDL-C, driven by chronic inflammation and insulin resistance. CKD progression, particularly obesity-related glomerulopathy (ORG), is also mediated by metabolic and hemodynamic derangements, including renin-angiotensin-aldosterone system activation and glomerular hyperfiltration. Therapeutic interventions such as lifestyle modification, pharmacological therapy - including glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) - and bariatric surgery have shown efficacy not only in promoting weight loss but also in improving the clinical course of these obesity-related conditions. In particular, Very Low Energy Ketogenic Therapy (VLEKT) is emerging as a promising approach in improving metabolic parameters, hepatic steatosis, and cardiovascular risk factors. A comprehensive and multidisciplinary approach to obesity is essential, focusing not only on weight loss but also on mitigating associated complications. Effective management can significantly improve patients' quality of life and reduce the long-term burden of obesity on healthcare systems.

暂无摘要（点击查看详情）

PURPOSE: Diabetic kidney disease (DKD) in type 1 diabetes has been shown to be strongly associated with insulin resistance, but this has not been previously explored using the euglycemic-hyperinsulinemic clamp. Therefore, we investigated insulin sensitivity in people with type 1 diabetes with and without DKD using M/I-values (mean glucose disposal rates [GDR]/mean plasma insulin) and compared GDRs to estimated GDR (eGDR)-formulae. METHODS: In this pilot study, we studied 17 adult individuals with type 1 diabetes (ten with and seven without DKD) using euglycemic-hyperinsulinemic clamps and assessed correlations between GDR and eGDR values. RESULTS: M/I-values were 62.5% lower in individuals with type 1 diabetes and DKD compared to those without DKD, albeit not statistically significant (0.16 ± 0.08 vs. 0.10 ± 0.08 mg/kg/min per mIU/L, P = 0.154). In the whole group (n = 17) eGDR by Williams et al. demonstrated the highest correlation with GDR (r = 0.35, P = 0.167), while eGDR by Januszewski et al. had the highest correlation in the DKD group (n = 10, r = 0.46, P = 0.177). CONCLUSION: Our pilot study suggests the possibility of increased insulin resistance in people with type 1 diabetes and DKD.

Hepatology is experiencing major shifts in disease etiologies and raising demand for multidisciplinary care. However, a globally harmonized framework defining core training content remains lacking. We aimed to develop a globally informed expert consensus framework for the content of core hepatology training, in order to provide a structured foundation for curriculum development. A two-round modified Delphi using the RAND/UCLA Appropriateness Method (RAM) was conducted. A comprehensive list of curriculum items was developed from international training standards, refined by a steering committee, and rated by a stratified international panel. Consensus was determined using medians and a disagreement index (DI), which classified curriculum items as essential, desirable, or optional. 456 experts completed Round 1, of whom 78.7% also completed Round 2. Consensus was strongest for foundational knowledge and core diagnostic skills, including interpretation of abnormal liver function and liver screening test results, and non-invasive fibrosis assessment (both DI=0). Management of major liver diseases was consistently prioritized as essential. Procedures with the highest endorsement for independent performance were paracentesis, transient elastography, variceal screening, and endoscopic variceal therapy. Consensus was limited for conventional ultrasonography and advanced interventions, reflecting regional variability in resources and scope of practice. Most experts (79.1%) supported formal training in research methodology, and the median recommended fellowship length was 24 months. Subgroup differences were mainly observed in selected resource-dependent or highly specialized items. This global consensus offers a priority-stratified outline of core hepatology training content providing a practical foundation for curriculum development and staged implementation across diverse health systems. Our study provides a consensus-based, priority-stratified framework for core hepatology training content that may inform curriculum development and local adaptation, given the growing global burden of liver disease and the heterogeneity of training standards. This framework may support curriculum mapping and local adaptation for trainees, program directors, professional societies, and policymakers, including in settings where structured hepatology training pathways are still evolving. In practical terms, these findings may assist educators and institutions in reviewing and refining national curricula and training structures. However, specific implementation decisions, including accreditation requirements and procedural training standards, will need to be adapted to local regulatory and resource contexts. Recognizing that these recommendations are based on expert consensus rather than outcome data and may be variably implementable in resource-limited settings, the next steps are pilot implementation in diverse settings, evaluation of trainee and patient outcomes, and iterative revision, supported by coordinated efforts from societies, governments, and training institutions.

Amylin is a peptide hormone co-secreted with insulin from pancreatic β-cells that plays a crucial role in glucose homeostasis. Amylin by inhibiting glucagon secretion, slowing gastric emptying, and reducing food intake improves blood glucose and insulin sensitivity. However, emerging evidence suggests that amylin may also contribute to β-cell dysfunction and the development of insulin resistance (IR) in type 2 diabetes (T2D). This review explores the dual roles of amylin in T2D pathogenesis and management, highlighting its therapeutic and pathogenic implications. High amylin levels are associated with amyloid fibril formation, β-cell cytotoxicity, and progression of T2D complications. Conversely, amylin analogues have been shown to improve glycemic control, promote weight loss, and enhance energy balance via dual activation of amylin and calcitonin receptors in the hypothalamus. Experimental and clinical data demonstrate that both detrimental and protective effects of amylin are depending on concentration, duration, and receptor interaction. Amylin and its analogues exhibit paradoxical actions in T2D, acting as both pathogenic and protective effects. While preclinical and limited clinical studies support their role in improving metabolic control, concerns about amyloidogenic toxicity persist. Therefore, further robust clinical trials are needed to clarify amylin's long-term safety and optimize its therapeutic potential in T2D management.

Advanced and progressive thyroid cancer (TC) such as radioiodine-refractory thyroid cancer (RAIR-TC), presents a significant clinical challenge due to its poorer prognosis and limited therapeutic options. Lenvatinib is an oral multi-targeted tyrosine kinase approved as first line for the treatment of RAIR-TC. We provide a comprehensive review of lenvatinib in the management of advanced thyroid cancer including RAIR-TC, poorly differentiated (PDTC), anaplastic (ATC) and medullary thyroid carcinoma (MTC). A search was carried out on PubMed up to July 2024 to identify all relevant studies. The research was performed using the terms "thyroid neoplasms" (MeSH Terms) AND "lenvatinib" (MeSH Terms). Lenvatinib demonstrated beneficial outcomes in treating RAIR-TC with most patients achieving either partial response or stable disease, which led to its approval by regulatory agencies worldwide. In PDTC, lenvatinib demonstrated potential therapeutic usefulness, whereas its efficacy as a monotherapy in ATC has yielded less consistent outcomes. However, in ATC the combination of lenvatinib with immune check point inhibitors (such as pembrolizumab) seem promising. In MTC, the available data is limited to phase II studies. Adverse effects of any grade occur in almost all lenvatinib-treated patients and mostly have a time specific sequence of occurrence. Therapy discontinuations due to adverse events are not uncommon, and in some cases, drug-related fatalities may occur. Lenvatinib demonstrated clinical efficacy and safety in both clinical trials and real-world studies for the treatment of patients with different types of thyroid cancer.

The aim of this study was to investigate the association of gestational weight gain with carotid artery intima-media thickness (IMT) during late pregnancy, and the association with metabolic parameters, pregnancy outcome and placental histological assessment. Pregnant patients admitted with signs of labor were prospectively recruited and categorized into two groups: Group 1 included women with excessive weight gain during pregnancy; Group 2 included women with gestational weight gain within recommended range. IMT of the carotid arteries was measured sonographically. Placental histopathology was assessed by an experienced pathologist. The study group included 59 women, 32 in group 1 and 27 in group 2. Mean carotid artery IMT was thicker in group 1 compared with group 2 (0.7 vs. 0.6 mm, P=0.028). Metabolic parameters including blood glucose and insulin resistance, using the homeostasis model assessment-insulin resistance (HOMA-IR) were also significantly higher in women with excessive weight gain during pregnancy as compared with group 2 (P=0.026 and P=0.045, respectively). Gestational age at delivery was similar in the two groups, while birthweight and the rate of macrosomia were significantly higher in group 1 than in group 2 (P=0.033 and P=0.014, respectively). Placental lesions consistent with fetal thrombo-occlusive disease were more prevalent in group 1 than in group 2. Excessive weight gain during pregnancy is associated with increased IMT of the carotid arteries that correlate with abnormal metabolic parameters, adverse pregnancy outcome and abnormal placental findings.

pH changes are a cardinal feature in metabolic disorders. Based on published literature, chronic metabolic acidosis is a major finding in type 2 diabetes (T2D), which is recently described as CMAD (chronic metabolic acidosis of T2D). Several disorders characterized by overt metabolic acidosis are recognized as T2D co-morbidities or are dual risk factors that pertain to their unique signs and symptoms in T2D. Over time, many terms were used for chronic metabolic acidosis (CMA) in different disorders. However, the lack of a unified term for CMA, delayed the recognition of CMAD as a prime feature of T2D, and the setting of the diagnostic criteria and management protocol for this disorder. Other than the classical diabetic complications, CMAD contributes to non-classical organ-specific local diabetic complications. Here we described the likely clinical features of CMAD in general, such as fatigue, tiredness, cramps, and aches, as well as organ/system-specific symptoms of T2D related to the liver, skeletal muscles, bones and joints, lungs, nervous system, eyes, kidneys and urinary tract, oral cavity and teeth, gastrointestinal tract, immune system, and skin. Diagnostic criteria and confirmatory tests are enlisted together with the laboratory tools used for pH estimation in different body compartments. Finally, a management protocol is proposed, which covers: 1) lifestyle (exercise, stress management); 2) nutrition (drinks, foods, and supplements); and 3) therapeutic pH correction: general proton pump inhibitor (PPI) and alkaline minerals; and organ-specific therapies with different modalities of action. In addition, the therapeutic potentials of nanomedicine and immune and gene therapies for pH correction are raised.

Reliable tools to quantify nutrition knowledge are crucial for planning education and prevention. We developed the Questionario delle Conoscenze Alimentari Italiano (QCAI) for Italian adults and assessed its reliability. A convenience sample of 165 participants (18-89 years; 70.9% women) completed a self-administered, 69-item questionnaire organized into four content sections (experts' recommendations; nutrient content of foods; healthy choices; meal frequency and labels) plus demographics. Participants completed the questionnaire at baseline (T0) and again after seven days (T1) under identical conditions. Internal consistency was evaluated with Cronbach's alpha (and KR-20 for dichotomous items). Temporal stability was assessed with intraclass correlation coefficients (ICC<inf>(2,1)</inf>) for section and total scores, Cohen's kappa (&#x3ba;) for items, and Bland-Altman analysis. Total-scale internal consistency was acceptable (Cronbach's &#x3b1;=0.757 for available items), but domain-level &#x3b1; values were heterogeneous and in some sections low (&#x3b1;: 0.307-0.638), indicating limited coherence of some subscales. Test-retest stability for the total score was moderate (ICC<inf>(2,1)</inf>=0.62), and 64.29% of items showed at least moderate agreement (&#x3ba;&#x2265;0.40). Age-stratified analyses showed no linear trend in the total score across groups (18-39, 40-59, &#x2265;60; P<inf>trend</inf>=0.26). QCAI is a low-cost instrument that shows moderate temporal stability and acceptable reliability for the total score in Italian adults. However, the low internal consistency observed in some domains limits the interpretability of section scores and highlights the need for item refinement and formal validation (content, construct, and criterion validity) against established measures before routine clinical or public-health use.

暂无摘要（点击查看详情）

Prenatal exposure to dioxin, a known endocrine disruptor, after the Seveso accident of 1976 has been associated with thyroid dysfunction, metabolic syndrome and semen quality reduction. Experimental exposure to dioxin in utero produced epigenetic endocrine modifications associated with reduction of semen quality, while in men epigenetic effects are not known. Our objective was to study, by a case control approach, the long-term epigenetic effects of prenatal dioxin exposure in 38 men whose mothers had been exposed to high doses of dioxin, serum median 52.0 ppt at exposure, and therefore who were exposed in utero, median 24.7 ppt at pregnancy, vs. 41 unexposed men. Bisulfite-converted DNA was hybridized onto illumina Infinium Methylation EPIC BeadChip and methylation differences were studied at both individual probe (DMPs) and gene region (DMRs) levels. We identified hypomethylation of the SPAG1 gene region and a slightly hypermethylated region containing genes of the HOXA family associated with thyroid and skeletal development. An elevated level of epigenetic drift was noted in the exposed group potentially contributing to disease risk. Epigenetic age acceleration did not show significant association with in-utero dioxin exposure. Additionally, we found heightened neutrophils and diminished natural killer cells in blood of dioxin exposed men. These observations are the first in the literature and align with the long-term semen quality reduction and alteration of thyroid homeostasic mechanisms reported in children exposed in utero to dioxin in Seveso. The actual dioxin background serum levels, 1.0-2.0 ppt, are much lower than those associated to these effects.

Survodutide represents an innovative approach to obesity management and metabolic-associated fatty liver disease (MAFLD). These conditions, often closely linked with type 2 diabetes (T2DM) and cardiovascular diseases, demand effective treatment strategies. Survodutide acts by targeting both GLP-1 and glucagon receptors. This new dual agonist offers potential transformative benefits, with early clinical trials showcasing significant weight loss and improvements in metabolic markers. Survodutide's mechanism of action includes appetite regulation, enhanced glucose metabolism, and increased energy expenditure, making it a promising option for those struggling with obesity and related health issues. This review assesses Survodutide's pharmacology, efficacy, and safety in MASH and obesity, while also outlining its broader metabolic and cardiovascular benefits. It compares Survodutide's dual-agonist mechanism and clinical performance with single-target incretin therapies to clarify its potential role in the evolving treatment landscape. While the initial results are promising, the review emphasizes the importance of continued research to fully understand Survodutide's long-term safety and effectiveness. Ongoing trials will provide critical insights into its overall impact, side effects, patient response, and cost considerations. This article highlights Survodutide's potential in the treatment of obesity and metabolic disordersand evaluates its place in therapy for seeking improved outcomes.

Real-time continuous glucose monitoring (RT-CGM) is widely used in patients with type 1 diabetes (T1D) to improve glycemic control by reducing postprandial glucose peaks and hypoglycemic episodes. In addition, traditional biomarkers such as glycated hemoglobin (HbA1c), glycated albumin, and fructosamine provide retrospective estimates of glucose regulation over varying timeframes. This study aimed to evaluate the correlation between these biomarkers and glycemic metrics obtained from two types of RT-CGM systems: an implantable sensor (Eversense E3) and subcutaneously inserted sensors (Dexcom G6 and Guardian 4). We analyzed data from 35 patients with T1D: 13 used the Eversense E3 system, and 22 used Dexcom G6 or Guardian 4. Mean blood glucose (MBG) and time in range (TIR) were assessed at multiple time points and correlated with HbA1c, glycated albumin, and fructosamine levels. In the Eversense group, no significant correlation was observed between CGM-derived metrics and any of the biomarkers. Conversely, in the Dexcom/Guardian group, MBG and TIR demonstrated significant correlations with all biomarkers, showing large effect sizes for HbA1c and fructosamine, and medium for glycated albumin. These findings suggest that the Dexcom G6 and Guardian 4 systems more reliably reflect established biochemical markers of mid- to long-term glucose control, while Eversense may be less consistent in this regard. This highlights the importance of sensor selection when interpreting CGM data for clinical or research applications in diabetes management.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a public health threat in Europe. With an estimated 30.4% prevalence among the adult population in the European Union and United Kingdom, it is the most common chronic liver disease and is closely linked to obesity and type 2 diabetes, which can be considered as indicator conditions. Despite the scale of the burden, the spectrum of MASLD, including its advanced form, metabolic dysfunction-associated steatohepatitis (MASH), is weakly represented-or even absent-from health policy and development agendas. Further, the extent to which regional and national clinical practice guidelines (CPGs) on other liver diseases and related fields incorporate information on MASLD/MASH prevention or management is unclear. In this Series paper, we reviewed policy attention to MASLD/MASH across the European Union and the United Kingdom. We report low policy readiness across European countries to address MASLD/MASH. Only two (7.1%), Romania and Sweden, had a subnational strategy, while 13 (46.4%) referenced MASLD/MASH in other national or subnational action plans, predominantly those for liver disease and obesity. No country included MASLD/MASH in its priority non-communicable disease list. Additionally, 15 (53.6%) countries had national MASLD/MASH CPGs, while 25 (89.3%) mentioned MASLD/MASH in other national CPGs, most often those for obesity, diabetes, cirrhosis, liver transplantation, and primary care, respectively. We conclude that MASLD/MASH remains insufficiently addressed from a policy perspective, which contributes to low readiness to address this public health threat.

暂无摘要（点击查看详情）