Reviews in Endocrine & Metabolic Disorders最新文献

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.

The prevalence of obesity is rising around the world, as the number of subjects dieting and experiencing weight loss followed by unintentional weight regain, the so-called weight cycling (WC). In this narrative review we sought to reveal the effects of WC on body composition as well as to evaluate if WC may represent a risk factor for sarcopenia and sarcopenic obesity. The relative changes in lean and fat compartments after WC have been shown to depend on several factors as the degree of energy deficit, the rate of weight loss and baseline body weight, as well as sex, age, physical activity and subject's metabolic or hormonal status. Effects of WC on body compartments may be underestimated depending on body composition measurements, interference of physical exercise, number of WC, age and population characteristics. Studies using the most precise methods to assess body composition changes, as well those with higher number of WC and/or including old subjects, show that with WC, lower fat free mass (FFM) is regained with a mismatch between muscle and fat. In addition, when WC is involuntary in old age, it drives and accelerates the age-related loss of FFM, in particular in frail populations. Finally, an association between WC and sarcopenia or sarcopenia obesity, was also observed when evaluating strength together with WC-related body composition changes. In conclusion WC may act as an accelerator of biological aging, and it could be further investigated as a potential risk factor for sarcopenia or sarcopenic obesity.

This review is to systematically explore the relationship between muscle dysfunction and diabetes in adults, and to examine the impact of glycemic variability on muscle health and the development of diabetes-related complications. The review was conducted using three databases: MEDLINE, Scopus, and EMBASE, targeting peer-reviewed journal articles written in English and published from January 2014 to September 2024. The methodological quality assessment of the eligible studies was conducted using Joanna Briggs Institute Critical Appraisal Checklists. A total of 17 studies were included. Most studies were undertaken in Asian countries (n = 11) and focused on adults with type 2 diabetes (n = 12). There were 8,392 adults with diabetes, and their mean age ranged from 52 to 75 years old. The measurements for muscle function and glycemic variability varied across studies. The research findings regarding the relationship between muscle dysfunction and glycemic variability metrics among adults with diabetes, both with and without complications were inconsistent. For adults with diabetes and sarcopenic obesity, poor glycemic control was identified as an independent risk factor for sarcopenic obesity. Additionally, all included studies were rated as moderate or high quality in relation to their methodology. In conclusion, this review underscores the complex and inconsistent relationship between glycemic variability and muscle dysfunction in older adults with diabetes. Poor glycemic management is a significant risk factor for sarcopenic obesity, highlighting the need for tailored interventions to improve glycemic control and muscle health in this population.

Tirzepatide, a dual GIP and GLP-1 receptor agonist, has shown significant metabolic benefits and weight reduction, but its anti-inflammatory effects have been less studied. This study was conducted in accordance with PRISMA guidelines, including observational (cohort) studies and randomized clinical trials that evaluated tirzepatide use and reported percentage changes in high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). A random-effects model was used. Seven randomized clinical trials and one observational study were included (six studies were eligible for meta-analysis). Compared to placebo, tirzepatide reduced hsCRP (mean difference [MD]: -32.9; 95% confidence interval [CI]: -33.6 to - 32.2; I²=15.3%) and IL-6 (MD: -17.8; 95% CI: -24.3 to - 11.3; I² = 1.6%). Levels of hsCRP were significantly reduced with tirzepatide at 15 mg (MD: -32.9; 95% CI: -33.6 to - 32.2; I²=4.4%), 10 mg (MD: -33.9; 95% CI: -50.3 to - 17.6; I²=41.8%), and 5 mg (MD: -20.3; 95% CI: -35.2 to - 5.3; I²=0%). Similarly, IL-6 levels were significantly reduced with tirzepatide at 5 mg (MD: -18.8; 95% CI: -32.9 to - 4.6; I²=17.2%), 10 mg (MD: -17.9; 95% CI: -28.2 to - 7.7; I²=2.1%), and 15 mg (MD: -16.8; 95% CI: -31.1 to - 2.6; I²=47.4%). This study demonstrated that tirzepatide use is associated with a significant reduction in inflammatory markers, regardless of the population studied or treatment regimen.

The development of drugs targeting Nutrient Stimulated Hormone receptors has ushered in a dramatic change in our approach to weight management because of their ability to achieve weight losses of 10%, 20%, even 30% in significant numbers of patients. Additionally, disease modifying properties of these medications are compelling. Indications now include cardiovascular risk reduction, obstructive sleep apnea and diabetes management, and emerging evidence supports efficacy for heart failure and chronic kidney disease. These medications would need to be taken long term and the population being treated will be older than the traditional weight management patient. Emerging evidence cautions that the loss of excessive lean mass with some of the newer medications may be problematic. This is not a concern for most patients who will need the medications, but it is a concern in an older population, since loss of muscle and bone accelerates and progresses past age 60. Of weight lost with semaglutide, approximately 45% is from lean mass, while with tirzepatide, it is 25%. Going forward, combining another NuSH such as glucagon or amylin with the GLP-1 receptor agonists may lessen loss of lean mass. Another approach under study is the use of MAPi - myostatin-activin pathway inhibitors. Promising results with bimagrumab are spurring investigaton in this area. For the full potential of disease modification to be achieved, it's a given that we must demonstrate safe, long term body composition improvement when the new medications are deployed, especially in the older population. This narrative review discusses the justification for focus on lean mass preservation and reviews the status of relevant drugs in development.

Obesity is a global health concern that impacts health, quality of life, and longevity in affected individuals. Comorbid cardiovascular disease, type 2 diabetes, cancer, and other conditions often accompany obesity, and researchers are actively investigating therapeutic strategies to treat obesity and mitigate the health risks associated with excess adiposity. Restrictive nutritional intake and body weight reduction through lifestyle behavioral interventions, bariatric procedures, and highly effective anti-obesity medications are all recommended treatments for obesity. Meanwhile, the caloric restriction that comes with very low-calorie diets can result in changes in body composition, most notably a progressive loss of muscle mass and/or functionality, a process that can be accelerated by aging, underlying metabolic disease, or inadequate protein intake seen with many dietary patterns. While muscle loss was previously understood as a condition only affecting older individuals, this outcome is common in patients with obesity. The term sarcopenic obesity has been used to refer to this condition, and it is now recognized as an important potential complication in all patients with obesity. Dietary challenges that influence overall body composition also have drawn attention to the gut microbiome, a topic of growing interest as there is an increasingly recognized interplay between diet, the metabolic actions of microorganisms in the gut that impact macronutrient and micronutrient production and absorption, and human health. This article will review the current understanding of obesity as a chronic disease, the impact of diet and nutritional therapy on body composition, and the potential relevance of the gut microbiome in this setting.

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.