Reviews in Endocrine & Metabolic Disorders最新文献

Obesity and type-2 diabetes mellitus (T2DM) are interrelated metabolic disorders primarily driven by overnutrition and physical inactivity, which oftentimes entails a transition from obesity to T2DM. Compromised musculoskeletal health consistently emerges as a common hallmark in the progression of these metabolic disorders. Skeletal muscle atrophy and dysfunction can further impair whole-body metabolism and reduce physical exercise capacity, thus instigating a vicious cycle that further deteriorates the underlying conditions. However, the myocellular repercussions of these metabolic disturbances remain to be completely clarified. Insulin signaling not only facilitates skeletal muscle glucose uptake but also plays a central role in skeletal muscle anabolism mainly due to suppression of catabolic pathways and facilitating an anabolic response to nutrient feeding. Chronic overnutrition may trigger different myocellular mechanisms proposed to contribute to insulin resistance and aggravate skeletal muscle atrophy and dysfunction. These mechanisms mainly include the inactivation of insulin signaling components through sustained activation of stress-related pathways, mitochondrial dysfunction, a shift to glycolytic skeletal muscle fibers, and hyperglycemia. In the present review, we aim to delve on these mechanisms, providing an overview of the myocellular processes involved in skeletal muscle atrophy and dysfunction under chronic overnutrition, and their contribution to the progression to T2DM.

Obesity is traditionally defined as "abnormal or excessive fat accumulation that presents a health risk," yet this definition lacks precision and fails to account for individual variability in body composition. The continued reliance on body mass index (BMI) as a diagnostic tool further complicates accurate assessment, as BMI does not differentiate between fat mass and lean mass. Emerging evidence highlights that health risks associated with obesity are not solely determined by fat accumulation, but also by the relative deficiency in fat-free mass, particularly muscle. Despite this, the role of muscle health in obesity management remains underappreciated in clinical practice. With the advent of potent pharmacotherapies for obesity, such as a new class of GLP-1 receptor agonists, there is growing concern about their impact on muscle mass during weight loss. This underscores the need for a more holistic understanding of body composition changes and their implications for long-term health. This special issue of Reviews in Endocrine and Metabolic Disorders addresses these critical gaps, offering diverse perspectives on integrating muscle health into the continuum of obesity care.

Hypothalamic pro-opiomelanocortin (POMC) neurons are classically viewed as mediators of satiety, acting in response to metabolic and hormonal cues and in opposition to Agouti-related protein (AgRP) neurons to maintain energy balance. This model, centered on the appetite-suppressant effects of the POMC-derived neuropeptide α-melanocyte-stimulating hormone (α-MSH) through its activation of melanocortin-4 receptors (MC4R), has shaped our understanding of feeding and body weight regulation for decades. However, recent discoveries have challenged and expanded this traditional view, revealing that POMC neurons are not a uniform population dedicated solely to satiety control. Single-cell transcriptomic analyses have revealed striking molecular heterogeneity, reflected in distinct anatomical distributions, receptor expression profiles, electrophysiological properties, and projection patterns - all supporting the idea of functional specialization within this neuronal population. In this review, we propose a conceptual framework that integrates POMC neuronal heterogeneity with the regulation of appetite, metabolic physiology, and behavior beyond feeding. We highlight emerging evidence showing that discrete POMC neuronal subpopulations respond to specific combinations of interoceptive and environmental cues to orchestrate diverse adaptive responses. This perspective underscores the developmental plasticity and functional versatility of POMC neurons, offering new insights into the mechanisms of obesity and potentially paving the way for novel targeted therapeutic strategies.

The regulation of energy homeostasis is an essential function of every living organism. In mammals a complex interplay of neural networks has evolved to ensure proper adaptation to energy demands, availability, consumption, storage and utilization. While a large set of parallel and redundant brain networks are functionally intertwined in these processes, a specific subset of hypothalamic neurons producing the agonist and antagonist of the anorectic signaling pathway controlled by the melanocortin receptor have been extensively studied. The anorectic/catabolic pro-opiomelanocortin (POMC) producing neurons and the orexigenic/anabolic Agouti-related peptide (AgRP) producing neurons exert opposing functions of various aspects of foraging, ingestive and post-ingestive processes. Located close to circumventricular these two populations integrate circulating reflecting energy status but are dynamically controlled by food-predicting cues. This review will be focusing on recent advances in understanding the role of the hypothalamic AgRP neurons, as critical metabolic sensors and regulators. We explore the intricate mechanisms by which these neurons integrate diverse nutritional signals and coordinate autonomic and behavioral responses to maintain metabolic equilibrium.

Childhood obesity is a global health problem, with its prevalence having tripled since 1975. The increase in its prevalence has been predominantly in developing countries, but also in those with high economic status. Nowadays, there are multiple obesity definitions, however, one of the most accurate is the one which defines obesity as the accumulation of excessive body adiposity and not as an body weight excess. Nevertheless, the body mass index (BMI) is the most frequently used tool for its classification, according to the cut-off points established by the Center for Disease Control and World Health Organization tables. In children and adolescents an adiposity excess is related to the appearance of cardiovascular disease in adulthood and with many comorbidities such as metabolic syndrome, insulin resistance, type 2 diabetes, hypertension and metabolic dysfunction-associated steatotic liver disease, among others. Currently, there is still controversy about which is the ideal indicator for measuring overweight and obesity. BMI is still used as a standardized measure but may miss cases in which body composition is pathological despite a BMI within the normal-weight category. An adequate knowledge of the impact on health of dysfunctional adiposity as well as its accurate diagnosis will allow health professionals to address this condition in a more precise and comprehensive manner, and substantially improve the associated cardiometabolic risk and prognosis.

Neuroendocrine tumors (NET) are frequently associated with glycemic disorders, such as prediabetes or diabetes, which may result from either surgical or medical treatments or hormonal hypersecretion by the tumor itself. Moreover, pre-existing diabetes is a known risk factor for NET development, with metabolic control and antidiabetic therapies potentially influencing tumor progression. The complex interplay between diabetes and NET, which share several molecular pathways, has spurred interest in the anti-cancer effects of antidiabetic medications. This is particularly relevant as new antidiabetic drugs continue to emerge, including sodium-glucose cotransporter-2 (SGLT2) inhibitors and incretin-based therapies, such as dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor (GLP-1R) agonists and dual GIP/GLP- 1 R agonists. This review explores the impact of these novel pharmacological options on NET development and progression through a comprehensive analysis of pre-clinical and clinical studies, with the purpose to evaluate safety and feasibility of introducing these drugs in the treatment of NETs patients. We conducted a comprehensive search of online databases, including PubMed, ISI Web of Science, and Scopus, for studies assessing the therapeutic effects and potential mechanisms of action of incretins and SGLT2 inhibitors in patients with NET. These novel antidiabetic drugs exhibit promising anticancer properties, potentially inhibiting tumor cell proliferation and inducing apoptosis, though concerns about certain cancer risks remain. Based on current evidence, the benefits of incretin-based therapies outweigh any potential cancer risks, leading to the proposal of tailored management algorithms for diabetes in NET patients, factoring in the diabetes aetiology, comorbidities, and life expectancy.

Thyroid inflammation during pregnancy, particularly Hashimoto's thyroiditis (HT) and postpartum thyroiditis (PPT), has a strong genetic and epigenetic basis. Susceptibility to these conditions is associated with specific HLA haplotypes (HLA-DR3, DR4, DR5) and immune-regulatory genes, including CTLA-4, PTPN22, FOXP3, as well as thyroid-specific genes such as TSHR, TG, and TPO. CTLA-4 polymorphism (CT60) is linked to increased thyroid autoantibody production, while PTPN22 R620W variant disrupts immune tolerance, exacerbating autoreactive lymphocyte activation.Epigenetic modifications play a crucial role in HT and PPT pathogenesis. Dysregulation of microRNAs (miRNAs), including miR-146a, miR-142, miR-301, and miR-155, affects immune pathways by modulating T-cell responses and inflammatory cytokine production. Aberrant DNA methylation in genes regulating immune function, such as FOXP3 and CTLA-4, contributes to altered immune tolerance and disease progression.Oxidative stress further modulates disease severity by inducing DNA damage and enhancing inflammatory responses, particularly in pregnancy. Reactive oxygen species (ROS) promote thyroid autoimmunity by affecting placental function and fetal neurodevelopment. Understanding the interplay between genetic susceptibility, epigenetic regulation, and oxidative stress is essential for developing personalized management strategies. This review highlights the molecular mechanisms underlying HT and PPT and the potential of epigenetic biomarkers for early diagnosis and targeted therapies.

The purpose of our study was to evaluate the efficacy and safety of partial adrenalectomy (PA) in the management of pheochromocytomas. A systematic review and metanalyses of all randomized controlled trials and observational studies (comparative and non-comparative studies), including case series with at least 5 cases, reporting efficacy and safety outcomes of PA in the treatment of bilateral and/or inherited pheochromocytomas was performed. A total of 33 articles were included in this systematic review, including 22 observational comparative and 11 single-arm studies. The pooled rates of biochemical and clinical cure after PA were 99.7% (95%CI: 98.7-100) and 99.8% (95%CI: 98.8-100), respectively. The pooled complication rate was 5.9% (95%CI: 0.8-10.9). Tumor recurrence and metastatic rates were 4% (95%CI: 0-1.6) and 0% (95%CI: 0.00-0.6), respectively. Steroid supplementation was required in 7.6% (95%CI: 2.8-12.5) of patients. No significant difference was detected in acute adrenal crisis (odds ratio [OR] 0.44, 95%CI: 0.16-1.22), biochemical (OR 0.42, 95%CI: 0.05-3.85) and clinical cure (OR 0.42, 95%CI: 0.05-3.85), complication (OR 1.59, 95%CI: 0.28-9.13) and metastatic rate (OR 1.56, 95%CI: 0.59-4.15) between the group of partial and total adrenalectomy. Nevertheless, recurrence rate (OR 2.55, 95%CI: 1.24-5.23) was higher with PA, while the need for supplementation rate (OR 0.01, 95%CI: 0.00-0.01) was significantly lower than in the total adrenalectomy group. The conclusion of the study is that the probability of biochemical cure and the rate of complications is similar between the group of patients who underwent total and partial adrenalectomy, but PA is associated with a lower rate of adrenal insufficiency and a higher recurrence rate than total adrenalectomy.

Insulin icodec is a novel once-weekly basal insulin analog subcutaneous injection seeking approval by the United States Food and Drug Administration (FDA) for use in both type 1 and type 2 diabetes mellitus. The mission of this manuscript is to provide a thorough overview of insulin icodec's clinical trials that were involved in its approval as well as review its pharmacology, pharmacokinetics, adverse effects, drug interactions, dosage recommendations, and regulatory issues. This article includes a thorough review of insulin icodec's safety and efficacy in type 1 and type 2 diabetes mellitus including its pharmacokinetic and pharmacodynamic profile. A systematic search of the electronic database of PubMed from inception until December 2024 using MeSH keywords was completed. Keywords used were icodec, insulin, type 1 diabetes, and type 2 diabetes. Overall, 14 clinical trials were identified and reviewed. The majority of the trials reviewed showed decreases in A1C as primary endpoints and non-inferiority and superiority with insulin icodec versus the comparator. In select studies, mild hypoglycemia was more evident in subjects taking insulin icodec versus the comparator but no other concerns were identified. The reviewed literature showed similar and sometimes improved glycemic control when insulin icodec was compared to other long-acting insulins both in insulin-naive and previously insulin-treated patients. Hypoglycemia was similar or slightly increased with insulin icodec when compared to other long acting insulins. Overall, icodec is a useful, new formulation of basal insulin that allows for less injections, improved compliance, and potentially improved glycemic control providing a new tool to practitioners managing patients with diabetes who need to be on insulin.

Despite bioelectrical impedance analysis (BIA)-derived phase angle (PhA) being recognized as a global marker of health, reflecting both cellular integrity and fluid distribution, its biological determinants still need to be described in youth. This narrative review provides a comprehensive framework examining to what extent dielectric properties shaping PhA are influenced by qualitative and quantitative determinants at multiple levels of body composition in healthy and clinical pediatric populations. At the atomic-molecular level, water content, glycogen, lipids, and ionic concentrations are expected to influence PhA by affecting electrical conductivity and/or capacitance. While the increase in the absolute values of intracellular (ICW) and extracellular water (ECW) enhances electric conductivity, an increase in the relative portion of ECW is expected to reflect hydration imbalances with an impact on electrical pathways. At the cellular level, body cell mass is a key determinant of PhA, mainly due to the presence of skeletal muscle cells favoring conductive and capacitive properties. At the tissue level, skeletal muscle architecture and orientation strongly influence conductivity, while increases in skeletal muscle mass positively impact PhA by enhancing electric conductivity and capacitance. Beyond the theoretical insights presented in this review, careful interpretation of dielectric data remains crucial due to the lack of methodological standardization. Future research should prioritize validated reference methods, investigate longitudinal changes, integrate localized BIA, and explore additional BIA models to refine the interpretation of PhA.