Background: Cardiovascular complications are a leading cause of death in patients with type 2 diabetes (T2D). The GLP-1 receptor agonist (GLP-1RA) semaglutide has shown cardiometabolic benefits in individual studies, but a comprehensive analysis of its effects in both oral and subcutaneous formulations is lacking. Objective: This study aimed to systematically evaluate the impact of semaglutide, in oral and subcutaneous formulations, on major adverse cardiovascular events (MACE) in patients with T2D. Methods: This review adhered to the PRISMA guidelines and included a comprehensive search of PubMed, MEDLINE, and Google Scholar from November 2016 to June 2025. High-quality randomized controlled trials (RCTs) comparing semaglutide with placebo in patients with T2D were included. The primary endpoint was MACE, defined as cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Hazard ratio (HR) and 95% confidence intervals (CIs) were pooled using a random-effects model. Results: Of the 127 articles screened, 3 trials involving 16,130 participants met the inclusion criteria. The pooled HR for MACE across the SOUL, SUSTAIN-6, and PIONEER-6 trials was 0.83 (95% CI: 0.76–0.92; I2 = 25%), indicating a 17% relative risk reduction with low heterogeneity. Adverse event profiles were comparable between the semaglutide and placebo groups. Conclusions: Semaglutide use was associated with a significant and consistent reduction in MACE in patients with T2D, supporting its role as a valuable therapeutic option for combined glycemic control and cardiovascular risk reduction.

Objectives: This study aimed to evaluate adherence to therapy in hypoparathyroidism and related endocrine–metabolic disorders and to assess its association with biochemical outcomes, hypocalcemia episodes, and health-related quality of life (HRQoL). Methods: In accordance with PRISMA 2020 guidelines, PubMed, Scopus, Google Scholar, and the Cochrane Library were searched until September 2025. The eligible studies were randomized controlled trials, cohort, case–control studies, cross-sectional, and observational studies that reported adherence to calcium/vitamin D or recombinant parathyroid hormone therapy. Results: twenty-three studies were included in the qualitative synthesis, and 11 studies were included in the quantitative meta-analysis. Pooled medication adherence compliance was 70–82% and improved with simplified regimens and the use of recombinant PTH. Additionally, this was also associated with an improvement in HRQoL (p < 0.0001) and a lower risk of hypocalcemia (p < 0.0001). Conversely, multifactorial regulation was observed as the level of adherence had no significant effect on serum calcium levels (p = 0.7116). Sensitivity analyses demonstrate the strength of findings and indicate no significant publication bias. Conclusions: Medication adherence is a key factor in determining patient-centered outcomes in hypoparathyroidism. Better adherence is linked to a higher quality of life and fewer episodes of hypocalcemia, while its effect on biochemical parameters seems minimal. Educational programs, simple treatment regimens, and wider access to rhPTH therapy can be used to improve patient management of the disease over time.

Background/Objectives: The association between gestational weight gain (GWG) and adverse outcomes in individuals with gestational diabetes mellitus (GDM) and obesity remains unclear. This study aimed to evaluate the relationship between total GWG and maternal, obstetric, and neonatal outcomes in patients with GDM, stratified by obesity class. Methods: This retrospective cohort included 695 pregnant individuals with GDM treated at a tertiary university hospital in Brazil between 2007 and 2021. GWG was categorized as insufficient, adequate, or excessive per National Academy of Medicine guidelines. Outcomes included maternal, obstetric, and neonatal events. Analyses were conducted for the entire cohort and stratified by obesity class (I and II/III), using multivariate regression models adjusted for maternal age, parity, and pre-pregnancy BMI. Results: The mean age was 33.6 (SD 5.7) years. GWG was insufficient in 33.2%, adequate in 28.2%, and excessive in 37.8%. Excessive GWG was associated with increased odds of cesarean delivery (OR 1.69; 95% CI 1.15–2.48) and large-for-gestational-age newborns (OR 3.29; 95% CI 1.61–6.46). As a continuous variable, GWG was positively associated with cesarean delivery (OR 1.04), LGA (OR 1.10), and birthweight (β = 0.02). Lower GWG was independently associated with reduced preeclampsia risk (OR 1.09 per kg). Insufficient GWG was not linked to increased risk of small-for-gestational-age newborns or other adverse outcomes and was associated with lower insulin requirement. Results remained consistent across obesity subgroups, except for cesarean delivery in class II/III obesity. Conclusions: In individuals with GDM and obesity, insufficient GWG was not associated with increased adverse outcomes, while excessive GWG was consistently linked to unfavorable maternal and neonatal risks. Stricter GWG control may be safe and beneficial in this population.

Background: Obesity has been proposed as a risk factor for differentiated thyroid carcinoma (DTC), though findings in the literature remain conflicting. While some studies suggest an association between elevated body mass index (BMI) and thyroid malignancy, others attribute this link to diagnostic bias. The Calabria region in Southern Italy, historically affected by iodine deficiency and endemic goiter, offers a valuable population for investigating this relationship. Objective: This study aimed to evaluate the association between obesity and clinical, sonographic, and cytological characteristics of thyroid nodules in a Calabrian cohort undergoing fine-needle aspiration biopsy (FNAB). Methods: This retrospective observational study included 1192 patients evaluated at a single endocrine referral center between 2015 and 2024. Patients were stratified by BMI (<30 vs. ≥30 kg/m2). Demographic, biochemical, ultrasound, and cytological data were collected and analyzed. Cytological results were classified according to the SIAPEC 2014 system. Results: Obese patients had significantly larger thyroid nodules in terms of anteroposterior and transverse diameters, as well as overall volume (p < 0.05). However, the distribution of high-risk cytological categories (TIR 3B, TIR 4, and TIR 5) did not differ significantly between obese and non-obese patients (9.4% in both groups). Multivariate analysis confirmed that BMI was not an independent predictor of malignancy risk (OR 0.988; p = 0.723), whereas younger age was inversely associated with malignancy. Conclusions: Obesity appears to influence thyroid nodule size but does not constitute an independent risk factor for cytological malignancy. BMI should not influence indications for FNAB or subsequent treatment decisions. Thyroid nodule management should instead rely on ultrasound risk stratification and cytological findings. Special attention should be given to younger patients as they may carry a higher malignancy risk.

Background/Objectives: Adequate sleep has a fundamental role in human health, mainly in cognitive and physiological functions. However, the daily demands of modern society have led to a constant pursuit of better living conditions, requiring more active hours at the expense of sleeping hours. This sleep deprivation has been associated with human health deterioration, namely an increase in Diabetes Mellitus incidence. This metabolic disease is a chronic pathology that imposes a big burden on health systems and is associated with the rise in insulin resistance. In this sense, the aim of this review is to analyze the relation between sleep deprivation and insulin resistance, emphasizing the metabolic parameters and hormones that may be involved in the subjacent mechanism. Methods: A literature review of the last 10 years was performed with specific terms related to “sleep deprivation” and “insulin resistance”. Results: Overall, the studies analyzed showed a decrease in insulin sensitivity in cases of sleep deprivation, even with different study protocols. In addition, an association between sleep deprivation and increased non-esterified fatty acids was also noticeable; however, other parameters such as cortisol, metanephrines, and normetanephrines showed no consistent results among the studies. Conclusions: This review allowed us to confirm the relationship between sleep deprivation and insulin resistance; however, despite the difficulties to monitor sleep, more research is needed to understand the related mechanisms that have not yet been clarified.

Remnant cholesterol, contained within triglyceride-rich lipoproteins such as VLDL and IDL, has emerged as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in both the general population and individuals with diabetes. Unlike LDL cholesterol, remnant cholesterol has not traditionally been a therapeutic target, despite growing evidence of its role in the pathophysiology of atherosclerosis. These particles exhibit high atherogenic and pro-inflammatory potential, and their metabolism is altered in states of insulin resistance and hepatic dysfunction, both common in diabetes. Epidemiological studies have shown its association with ischemic heart disease, peripheral artery disease, progression of nephropathy, and cardiovascular events in type 2 diabetes. In individuals with type 1 diabetes (T1D), the evidence is more recent but relevant: elevated levels of remnant cholesterol have been linked to persistent hyperglycemia, diabetic nephropathy, diabetic foot, subclinical myocardial dysfunction, and carotid atherosclerosis, even when LDL-C levels are within target range. Moreover, lifestyle factors such as physical activity and a healthy diet are associated with lower levels of remnant cholesterol, suggesting opportunities for non-pharmacological interventions. Despite this, treatments targeting remnant cholesterol have shown limited efficacy in reducing clinical events, and individuals with T1D remain underrepresented in clinical trials. Overall, this review highlights the need to incorporate remnant cholesterol into the assessment of residual cardiovascular risk and into personalized therapeutic strategies, especially for vulnerable populations such as those with T1D.

Background/Objectives: Anthropometric indices based on height (H), weight (W), waist circumference (WC) and hip circumference (HC) can identify incident and future health risks. While BMI provides a standard for relative W (adjusted for H), there is no standard for indices using WC and HC. A body shape index (ABSI) and hip index (HI) have been proposed to extend to respectively WC and HC the same allometric power-law approach used to derive BMI to be independent of H. Here, we compared the mutually independent allometric set H, BMI, ABSI, HI with other proposed indices. Methods: We examined the formulas and rationales of published indices, and used Third National Health and Nutrition Examination Survey (NHANES III) cohort data to investigate their inter-correlations and association with mortality. Results: Many of the proposed indices are based on geometric (isometric) similarity, which does not match human body variability patterns. Unlike ABSI and HI, most proposed indices showed large correlations with BMI, complicating interpretation when considered together with BMI. Indices’ association with mortality risk were generally consistent with their correlations with BMI and ABSI. Combining the separable mortality risks associated with BMI and ABSI, even in a simplified way, outperformed any single index. Conclusions: With calls for incorporating additional indices incorporating WC and HC to supplement BMI in defining obesity, only ABSI and HI are independent of BMI. Additionally, separate risk estimates from these allometric indices can be readily combined to optimize overall risk assessment.

Background: Plastic pollution driven by human activities has become a critical global issue for human health. A growing literature demonstrates that micro- and nanoplastics (MNPs) contain endocrine-disrupting chemicals (EDCs) and other harmful compounds that enter the body easily, acting as agonists or antagonists for a wide range of hormonal receptors, and promoting endocrine toxicity. Endocrine disruption induced by MNPs occurs through the aberrant activation/inhibition of different signaling pathways that in addition to directly interfering with hormonal balances, trigger apoptosis, oxidative stress, and inflammation in endocrine cells. However, to date, the molecular mechanisms of these contaminants remain not completely elucidated. Furthermore, given the unanimous consensus on the negative impact of MNPs on human health, several methodologies have been developed to detect MNPs and contaminants not only in the environment but also in biological fluids and human tissues. Results: This review comprehensively summarizes the emerging experimental and clinical evidence explaining the mechanisms underlying the toxicity related to chronic plastic pollution in relation to the endocrine system. In addition, the review illustrates the new methodological approaches to detect MNPs in human biological samples, highlighting that employing complementary methods enables the precise characterization and quantification of MNPs. Conclusions: Future studies employing experimental, epidemiological, epigenetic, and multi-omics approaches are essential for understanding the short and long-term effects of MNPs on endocrine glands and developing effective strategies to mitigate their impact on human health.

Background: Oncocytic adenomas (OAs) of the thyroid, previously referred to as Hürthle cell adenomas, are uncommon tumors, particularly in pediatric populations, where they represent a minority of thyroid nodules. Due to their rarity and the potential difficulty in distinguishing benign from malignant forms on cytology, these adenomas present unique diagnostic and management challenges. Here, we report a pediatric case of a large OA of the thyroid, managed with surgical resection following inconclusive fine-needle aspiration (FNA) results. Case Presentation: A 13-year-old girl presented with an enlarging thyroid nodule. An ultrasound examination showed a large (26 × 16 mm), solid, isoechoic nodule with a hypoechoic halo. The FNA findings were inconclusive, indicating a follicular neoplasm with oncocytic features, classified as Bethesda IV. The patient underwent a hemithyroidectomy, and a histopathological examination confirmed an encapsulated OA without evidence of capsular or vascular invasion. The postoperative recovery was uneventful, and follow-up assessments showed no recurrence. Conclusions: OAs in pediatric patients are rare and may pose diagnostic challenges. This case highlights the importance of a comprehensive approach, including surgical resection, for definitive diagnoses in cases where FNA results are inconclusive. Further studies are warranted to establish guidelines for the management of oncocytic thyroid neoplasms in pediatric patients, as well as to understand their clinical behavior in this population.

Introduction: Early-life neurological and inflammatory disorders significantly affect long-term cognitive, social, and emotional development. The ‘Developmental Origins of Health and Disease’ hypothesis states that an adverse intrauterine environment may predispose offspring to chronic health conditions due to altered growth and development. Factors measured in umbilical cord blood can provide information about the status of the in utero environment during development. Evidence indicates that umbilical cord blood adipokines, namely leptin and adiponectin, may influence fetal programming and could be useful in predicting offspring health outcomes. Leptin and adiponectin are crucial in energy homeostasis, immune response, and placental function, and some studies suggest that altered concentrations may increase the risk of developing inflammatory and neurological disorders in later life. Further, limited studies have demonstrated sex-specific differences in adipokine concentrations and disease risk. Conclusions: Understanding the role of umbilical cord blood adipokines in fetal programming could offer new insights into early risk prediction and intervention strategies, promoting better health outcomes for children at risk of neurological and inflammatory diseases due to an adverse maternal environment during pregnancy.