Reviews in Endocrine & Metabolic Disorders最新文献

Diabetic foot ulcers (DFUs) are among the most serious complications of diabetes mellitus, often resulting in infection, amputation, and increased mortality. Early detection is essential but remains difficult due to the complex interaction of neuropathy, vascular disease, and immune dysfunction. This review examines the effectiveness of thermal imaging, including approaches supported by artificial intelligence (AI), as a non-invasive tool for identifying early signs of DFUs. A total of 49 studies published between 1991 and 2024 were analysed, focusing on adult patients and primary research only. Findings show that thermal imaging can detect abnormal skin temperature patterns and early inflammation, key indicators of DFU development. AI techniques, such as machine learning and neural networks, further enhance diagnostic accuracy by identifying subtle patterns and predicting ulcer risk. Despite promising results, several limitations were noted: lack of standardised imaging protocols, inconsistent equipment quality, and small sample sizes in many studies. To improve clinical reliability, future work should focus on developing standard procedures, integrating AI with high-resolution thermal cameras, and validating these systems in real-world hospital and home-care settings. Overall, thermal imaging, especially when combined with AI, shows strong potential as a practical, non-invasive method for early DFU detection and monitoring.

The central nervous system is a key regulator of energy and glucose homeostasis, integrating peripheral signals such as hormones and nutrients to maintain metabolic balance. Among its regions, the hypothalamus plays a central role in monitoring energy status and orchestrating physiological responses via neuronal and glial circuits. Recent research highlights the influence of de novo ceramide synthesis on central nervous system regulation of metabolism. Indeed, ceramides have emerged as critical signalling molecules linking fatty acid sensing to hypothalamic control of feeding, energy expenditure, and glucose regulation. This review details the mechanisms of de novo ceramide synthesis and explores how dysregulation of this pathway in the hypothalamus contributes to obesity and type 2 diabetes. Serine palmitoyl-transferase and specific ceramide synthase isoforms are shown to play roles in mediating neuronal responses to metabolic stress. The findings also emphasize that hypothalamic ceramide metabolism is modulated by both nutritional and hormonal cues and suggest that targeting this pathway may offer new strategies for treating metabolic disorders.

Astrocytes, once viewed primarily as supportive cells in the central nervous system, are increasingly recognized as dynamic regulators in the regulation of systemic metabolism, especially within the hypothalamus. Recent research highlights their capacity to sense and integrate nutrient, hormonal, and circadian signals, modulate hypothalamic circuits, and ultimately influence whole-body energy balance. In this review, we discuss emerging studies that explore how hypothalamic astrocytes regulate glucose and lipid metabolism through neuroendocrine and autonomic pathways that extend their influence to peripheral organs. We examine emerging evidence showing that astrocytes contribute to glycemic control via glucose sensing, intracellular metabolic shifts, and modulation of key neuronal circuits. Similarly, recent investigations have identified roles for astrocytes in the regulation of adipose tissue function and body weight, particularly in the context of high-fat diet exposure, largely through their influence on hypothalamic neuron-astrocyte interactions and sympathetic output. We further consider recent findings implicating astrocytic circadian pathways in the coordination of metabolic rhythms, as well as the long-term consequences of early-life nutritional exposures, that may epigenetically program hypothalamic astrocyte function. New insights also point to region-specific and sex-dependent astrocytic functions. Together, this growing body of work positions hypothalamic astrocytes as integrators of brain-body communication in the control of energy homeostasis and highlights their potential relevance in the pathophysiology of obesity and metabolic disease.

The hypothalamus plays a central role in regulating energy balance, and its dysfunction is a key contributor to the development of metabolic diseases such as obesity and type 2 diabetes. Although peripheral inflammation has been extensively studied, hypothalamic inflammation, termed hypothalamic microinflammation, has emerged as a critical early event in the pathogenesis of these diseases. This localized, moderate, yet sustained inflammatory response involves a complex interplay between different cell types, including microglia, astrocytes, neurons, and tanycytes, which exhibit temporal and dynamic changes. Hypothalamic microinflammation is triggered by various metabolic stressors, including high-fat diets, aging, and glial priming, and occurs even before peripheral tissues show signs of inflammation. In this review, we propose a conceptual framework that divides the progression of hypothalamic microinflammation into three distinct phases: the Initiation Spark, characterized by rapid inflammatory signaling; the Adaptive Transition, where compensatory mechanisms attempt to restore homeostasis; and the Dysfunctional Phase, leading to chronic inflammation and metabolic dysfunction. Despite significant progress in understanding hypothalamic inflammation, several critical questions remain, including the precise triggers of this response, the chronology of molecular and cellular events, and the reversibility of early changes. Additionally, emerging evidence suggests that sex differences influence the susceptibility and progression of hypothalamic microinflammation, further complicating our understanding. This review examines the dynamics of hypothalamic microinflammation, its impact on brain and peripheral insulin resistance, and its role in disrupting energy balance. Understanding these processes is crucial for identifying therapeutic targets and early intervention windows to prevent or reverse metabolic diseases.

Over the past five decades, clinical and experimental data have established that iron metabolism, lipid metabolism, and obesity are intricately linked and differentially influence one another through complex metabolic pathways. Iron dyshomeostasis is now recognized as a key modulator of lipid metabolism, with profound implications for obesity and related metabolic disorders. Likewise, lipid metabolism and obesity significantly impact iron absorption and recycling. Although this interplay between iron metabolism, lipid metabolism, and obesity is complex, modulation of hepcidin synthesis seems to be the core link between these variables. As the global prevalence of metabolic disorders continues to escalate, understanding their multifactorial etiology has become a public health priority. Emerging evidence highlights the dysregulation of lipid metabolism as a central driver in the onset and progression of these conditions, with iron metabolism playing a crucial regulatory role. This review explores the relationship between iron metabolism on one hand and lipid metabolism and obesity on the other with specific emphasis on the molecular mechanisms underlying this relationship. The review also explores the bi-directional relationship between iron metabolism and mitochondrial functions, mainly energy production. It concludes by outlining the pathophysiological consequences of disrupted iron metabolism, vis-a-vis lipid metabolism, obesity, and diabetes. By synthesizing current knowledge, this review aims to provide new insights that could guide the development of novel therapeutic strategies to manage obesity, diabetes, and related metabolic disorders.

The global prevalence of obesity among elderly patients continues to rise. Despite the availability of new antiobesity medications, bariatric surgery remains an effective treatment option for carefully selected candidates. However, it is not risk-free, especially in a vulnerable population, predisposing to falls, fractures and sarcopenia. Following bariatric surgery, there is rapid loss of muscle mass, particularly within the first 3 months. Muscle quality, on the other hand, characterized by functionality and indirectly assessed through strength tests, appears to be preserved. This is attributed to reductions in ectopic intramuscular fat deposits. Strategies to mitigate muscle loss and functional impairment include combined exercises (resistive and aerobic training), adequate protein and vitamin D intake, beta-hydroxy-beta-methylbutyrate (HMB) supplementation, and testosterone replacement therapy for men with confirmed hypogonadism. It is important to emphasize that, to date, no specific trial has evaluated the current sarcopenia criteria in elderly patients undergoing bariatric surgery. Therefore, future studies are needed to assess this particularly vulnerable population, not only to monitor changes in muscular health, but also to develop strategies for preventing therapeutic inertia.

People with type 2 diabetes (T2D) have a 2-3-time higher risk of developing sarcopenia, a musculoskeletal disease marked by a progressive loss of skeletal muscle mass and strength, compared to people without T2D. This narrative review examines the effectiveness of lifestyle interventions in enhancing muscle mass and strength in people with T2D, emphasizing their growing importance with advancements in obesity treatments. PubMed and Google Scholar were utilized to identify the most relevant published studies based on the authors' knowledge. The maintenance of skeletal muscle strength and mass in people with T2D is becoming more prominent due to the advent of weight loss therapies such as low-energy diets, bariatric surgery and pharmacotherapies. Although the weight loss is to be commended, a large proportion (20-50%) of the weight loss comes from lean mass, indicative of a loss in muscle mass. There are currently no pharmacotherapies to increase, or mitigate the loss of, lean mass, with lifestyle strategies prominent in this arena. Resistance exercise is the most effective method to increase muscle mass and strength in people with T2D, but there is some evidence of an anabolic resistance. Aerobic exercise and increased dietary protein intake may result in small increases in muscle mass and strength, with no evidence of an anabolic resistance to these stimuli. Exercise and protein supplementation can increase, or aid in the retention of, muscle strength and mass in individuals with T2D, but further research is needed to explore their benefits in patients undergoing concomitant pharmaceutical and surgical treatments.

Across the spectrum of weight regain, ranging from cachexia rehabilitation and catch-up growth to obesity relapse, the recovery rate of body fat is often disproportionate relative to lean tissue recovery. Such preferential 'catch-up fat' is in part attributed to an increase in metabolic efficiency and embodied in the concept that 'metabolic adaptation' or 'adaptive thermogenesis' in response to large weight deficits can persist during weight regain to accelerate fat stores recovery. This paper reviews the evidence in humans for the existence of this thrifty metabolism driving catch-up fat within the framework of a feedback loop between fat stores depletion and suppressed thermogenesis. The search for its effector mechanisms suggests that whereas adaptive thermogenesis during weight loss results primarily from central suppression of sympathetic nervous system and hypothalamic-pituitary-thyroid axis, its persistence during weight regain for accelerating fat recovery is primarily mediated through peripheral tissue resistance to the actions of this systemic neurohormonal network. Emerging evidence linking it to an upregulation of skeletal muscle type 3 deiodinase (D3), the main thyroid hormone inactivating enzyme, along with slowed muscle metabolism and altered contractile properties, suggest that D3-induced muscle hypothyroidism is a key feature of such peripheral resistance. These findings underlying a role of skeletal muscle hypothyroidism in adaptive thermogenesis driving catch-up fat, but which can also concomitantly compromise muscle functionality, have been integrated into a mechanistic framework to explain how weight cycling and large weight fluctuations across the lifespan can predispose to sarcopenic obesity.

Poor muscle quality (MQ) is a hidden health condition in obesity, commonly disregarded and underdiagnosed, associated with poor health-related outcomes. This narrative review provides an in-depth exploration of MQ in obesity, including definitions, available assessment methods and challenges, pathophysiology, association with health outcomes, and potential interventions. MQ is a broad term that can include imaging, histological, functional, or metabolic assessments, evaluating beyond muscle quantity. MQ assessment is highly heterogeneous and requires further standardization. Common definitions of MQ include 1) muscle-specific strength (or functional MQ), the ratio between muscle strength and muscle quantity, and 2) muscle composition (or morphological MQ), mainly evaluating muscle fat infiltration. An individual with obesity might still have normal or higher muscle quantity despite having poor MQ, and techniques for direct measurements are needed. However, the use of body composition and physical function assessments is still limited in clinical practice. Thus, more accessible techniques for assessing strength, muscle mass, and composition should be further explored. Obesity leads to adipocyte dysfunction, generating a low-grade chronic inflammatory state, which leads to mitochondrial dysfunction. Adipocyte and mitochondrial dysfunction result in metabolic dysfunction manifesting clinically as insulin resistance, dyslipidemia, and fat infiltration into organs such as muscle, which in excess is termed myosteatosis. Myosteatosis decreases muscle cell function and insulin sensitivity, creating a vicious cycle of inflammation and metabolic derangements. Myosteatosis increases the risk of poor muscle function, systemic metabolic complications, and mortality, presenting prognostic potential. Interventions shown to improve MQ include nutrition, physical activity/exercise, pharmacology, and metabolic and bariatric surgery.

Obesity adversely impacts musculoskeletal health, contributing to functional limitations and an increased risk for falls, fractures and disability. Weight loss can mitigate these effects, but strategies that neglect to incorporate evidence-based dietary and/or exercise approaches can exacerbate musculoskeletal and functional declines. Sustainable weight loss requires a personalised approach that prioritises adequate protein intake and essential nutrients to preserve musculoskeletal health. To enhance adherence and long-term success, dietary strategies should be practical, nutritionally balanced and cost-effective. Similarly, exercise programmes should be individually tailored and progressive, with resistance training central to any program prescribed in the context of weight loss, due to its critical role in maintaining muscle and bone mass and strength. When prescribing weight loss strategies involving lifestyle behaviour changes, clinicians must consider their patient's readiness to change. We have used the transtheoretical model of change framework as an example to identify a patient's level of readiness and provided associated motivational interviewing-based strategies to enhance adherence and engagement. This review outlines evidence-based, practical diet and exercise recommendations and behavioural strategies that can facilitate effective and sustainable weight loss, which is particularly important for at-risk populations such as older adults.