Nature Reviews Endocrinology最新文献

{"title":"The pathogenesis and intersecting mechanisms of monogenic bone mass disorders","authors":"Raja Padidela, Gretl Hendrickx, Geert Mortier, Outi Mäkitie","doi":"10.1038/s41574-026-01260-x","DOIUrl":"10.1038/s41574-026-01260-x","url":null,"abstract":"Monogenic disorders of bone mass arise from variants in single genes disrupting the intricate processes of bone formation and resorption. Genes underlying bone mass disorders are involved in various intersecting molecular mechanisms in cells of the mesenchymal and haematopoietic lineages. Signalling pathways, including WNT–β-catenin, TGFβ–BMP and NF-κB, have central roles in bone metabolism, and variants in their regulators or effectors can have opposing effects on bone mass. Defects in osteoblast differentiation, collagen biosynthesis and extracellular matrix mineralization primarily drive the pathogenesis of low bone mass (LBM) conditions, exemplified by various forms of osteogenesis imperfecta. Conversely, impaired osteoclast differentiation and function, or enhanced osteoblastic activity underlie high bone mass (HBM) disorders, such as osteopetrosis and osteosclerosis. A subset of genes have pleiotropic effects, contributing to both LBM and HBM disorders depending on the genetic background. Advances in genetics have not only elucidated pathogenic mechanisms, but also enabled the development of targeted therapies, including anti-sclerostin antibodies and enzyme replacement therapies. However, most LBM and HBM conditions still have no cure. Understanding the shared and divergent mechanisms of bone mass regulation will offer insights into future therapeutic strategies. Advances in gene discovery, disease classification and targeted therapies are rapidly reshaping our understanding of monogenic disorders of low and high bone mass. In this Review, Padidela and colleagues discuss the intersecting molecular mechanisms within mesenchymal and haematopoietic cell lineages that disrupt the intricate processes of bone formation and resorption, causing these phenotypes.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 8","pages":"490-506"},"PeriodicalIF":39.1,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in diagnosing and treating diabetic retinopathy","authors":"Sobha Sivaprasad, Stela Vujosevic","doi":"10.1038/s41574-026-01257-6","DOIUrl":"10.1038/s41574-026-01257-6","url":null,"abstract":"Diabetic retinopathy has traditionally been defined as a microvascular complication of diabetes mellitus; however, advances in retinal imaging, digital technologies and mechanistic insights have challenged this narrow view. Increasing evidence indicates that neuronal and glial dysfunction and degeneration, neuroinflammation, capillary non-perfusion and metabolic dysregulation can occur early in the disease process and can precede or coexist with clinically apparent vascular abnormalities. These insights support the emerging concept of diabetic retinal disease (DRD), which encompasses the full spectrum of diabetes mellitus-related retinal pathology, with or without visible microvascular lesions. In this Review, we summarize the evolution of disease classification and advances made within the past 10 years in diagnostic imaging that enable more precise phenotyping and risk stratification of DRD. We also present a framework for a digitally enabled care pathway spanning screening, diagnosis, treatment and post-treatment follow-up. Finally, we discuss current therapies alongside emerging preventive and personalized treatment strategies that target both vascular and neuroretinal components across the full DRD disease continuum. In this Review, the authors discuss advances in imaging and treatment that are improving outcomes for patients with diabetic retinopathy. The authors also discuss technological advances in areas such as remote monitoring and telehealth that could expand access to care for these patients.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 8","pages":"477-489"},"PeriodicalIF":39.1,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highlights from SfE BES 2026","authors":"Olivia Tysoe","doi":"10.1038/s41574-026-01256-7","DOIUrl":"10.1038/s41574-026-01256-7","url":null,"abstract":"","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 7","pages":"386-386"},"PeriodicalIF":39.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical obesity in Asian people: bridging the gap between adiposity and disease","authors":"Soo Lim, Linong Ji, Kwang Wei Tham, Anoop Misra, Takashi Kadowaki","doi":"10.1038/s41574-026-01239-8","DOIUrl":"10.1038/s41574-026-01239-8","url":null,"abstract":"This Perspective argues for a reconceptualization of clinical obesity in Asian populations, moving beyond BMI-centric definitions towards an adiposity-based and function-based framework. Asian populations exhibit a distinctive obesity phenotype, characterized by excess visceral and ectopic adipose tissue accumulation, reduced β-cell reserve, sarcopenic obesity and heightened cardiometabolic risk at lower BMI thresholds than for white European and North American populations, leading to systematic under-recognition of obesity-related disease when conventional criteria are applied. Building on the Lancet Commission’s framework for defining and diagnosing clinical obesity, we propose an integrated approach that combines anthropometric measures, body composition assessment, metabolic and organ-specific markers and emerging biomarkers to distinguish preclinical obesity from clinical obesity on the basis of organ dysfunction and functional impairment. This approach improves risk stratification, supports earlier and more precise diagnosis and informs stage-specific management, including lifestyle intervention, pharmacotherapy and metabolic surgery, particularly in Asian populations. We discuss implications for clinical practice, prevention strategies and public health policy, emphasizing the need to align clinical guidelines, reimbursement systems and education with a function-based definition of obesity. Finally, we highlight key research priorities, including validation of biomarker-driven classifications, assessment of long-term clinical and economic outcomes and development of scalable diagnostic tools, to advance precision care and metabolic health equity across diverse Asian populations. The need to consider factors beyond BMI to accurately assess metabolic dysfunction when diagnosing and treating obesity is increasingly recognized. In this Perspective, Lim and colleagues advocate for an approach to assessments for obesity in Asian populations that takes ethnicity-specific factors into account.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 10","pages":"615-624"},"PeriodicalIF":39.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147753252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathophysiology, diagnosis and management of secondary osteoporosis","authors":"Julien Paccou, Elena Tsourdi, Athanasios D. Anastasilakis, Willem F. Lems, Juliet Compston","doi":"10.1038/s41574-026-01252-x","DOIUrl":"10.1038/s41574-026-01252-x","url":null,"abstract":"Age-related decline in sex hormones is the most frequent cause of primary osteoporosis; however, secondary causes contribute to osteoporosis in a substantial proportion of cases. These causes are diverse and often overlooked, ranging from endocrine diseases to chronic inflammatory conditions and medication use. The identification and exclusion of secondary causes of osteoporosis is crucial, because treatment typically begins by addressing the underlying condition. Investigation to exclude common secondary causes is recommended for everyone presenting with fractures indicative of osteoporosis. Advanced investigations are reserved for premenopausal individuals and those aged <50 years, and for older people in whom common risk factors, comorbidities or drugs predisposing to osteoporosis are absent. The risk of fracture can be underestimated by bone mineral density in some chronic diseases and overestimated in others. Specific adjustments can be made to the criteria in the online fracture risk FRAX calculator to provide a more accurate estimation of fracture risk in people with some forms of secondary osteoporosis. The response to conventional anti-osteoporosis treatments can be suboptimal if the underlying condition remains unrecognized and untreated. In most conditions, the evidence for antiresorptive or anabolic therapy is based on changes in bone mineral density rather than fracture. This Review covers the aetiology, pathogenesis, diagnosis and management of secondary osteoporosis, together with key areas for future research. Secondary osteoporosis, in which medication use and chronic medical conditions contribute to bone fragility, is a common but under-recognized form of the disease. In this Review, Paccou et al. discuss the aetiology, pathogenesis, diagnosis and management of secondary osteoporosis, together with key areas for future research.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 8","pages":"452-462"},"PeriodicalIF":39.1,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147726029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision medicine in low-income settings and small island developing states","authors":"Sushant Saluja, Fahmida Mannan, Guillaume Pare, Sonia S. Anand, Neil A. Hanchard, Claudia Langenberg, Simon G. Anderson","doi":"10.1038/s41574-026-01250-z","DOIUrl":"10.1038/s41574-026-01250-z","url":null,"abstract":"Precision medicine tailors prevention, diagnosis and treatment of cardiometabolic diseases to individual genetic, environmental and lifestyle determinants, with the potential to fundamentally change healthcare. However, low-income and middle-income countries (LMICs) and small island developing states (SIDS) experience severe implementation barriers: inadequate healthcare infrastructure, prohibitive costs, under-representation in genomic datasets and additional SIDS-specific constraints. This Perspective advances three specific contributions beyond generic equity calls. First, it delineates distinct precision medicine pathways for larger LMICs versus SIDS, highlighting SIDS opportunities for regional consortia, shared sequencing and/or biobanking hubs and technological leapfrogging via mobile health platforms and digital phenotyping. Second, it emphasizes practical and high-impact entry points that are financially sustainable. Additionally, it advocates for integrating polygenic risk-based stratification into existing non-communicable disease care pathways rather than establishing separate specialist services. Third, it delineates a staged implementation framework that prioritizes ethical oversight and robust data governance, underscoring the importance of privacy safeguards, data sovereignty, equitable benefit sharing, community consent mechanisms and alignment with the Sustainable Development Goals to minimize associated risks of exploitation. Equitable partnerships between LMICs and high-income countries, expansion of diverse genomic data and community-driven innovation will ensure that precision tools effectively target metabolic phenotypes in LMICs and SIDS while advancing global health equity. Precision medicine has the potential to radically improve diagnosis and treatment of cardiometabolic diseases in low-income and middle-income countries (LMICs) and small island developing states (SIDS). This Perspective discusses the challenges and complexities as well as the opportunities and advantages of implementing precision medicine in LMICs and SIDS.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 9","pages":"554-564"},"PeriodicalIF":39.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of hypoglycaemia on neurodevelopment: insights from congenital hyperinsulinism","authors":"Pamela Bowman, Jonna M. E. Männistö, Sarah E. Flanagan","doi":"10.1038/s41574-026-01253-w","DOIUrl":"10.1038/s41574-026-01253-w","url":null,"abstract":"Infants exposed to hypoglycaemia are at risk of neuroglycopenia and long-term neurodisability. Individuals with congenital hyperinsulinism provide a unique opportunity to gain insights into relevant biological pathways and outcomes. Such insights could transform clinical care for infants at risk of hypoglycaemia from a variety of genetic and environmental aetiologies.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 6","pages":"319-320"},"PeriodicalIF":40.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurokinin receptor antagonists for vasomotor symptoms: from KNDy neurons to clinical translation","authors":"Encarnación Torres, Ellen G. Wall, Víctor M. Navarro","doi":"10.1038/s41574-026-01247-8","DOIUrl":"10.1038/s41574-026-01247-8","url":null,"abstract":"Vasomotor symptoms (VMS), including hot flushes and night sweats, affect approximately 70% of people experiencing menopause and have a notable effect on quality of life. Until the past few years, the underlying neuroendocrine mechanisms remained poorly understood, limiting therapeutic options beyond menopausal hormone therapy. The discovery that neurons expressing kisspeptin, neurokinin B and dynorphin (KNDy neurons) in the hypothalamic arcuate nucleus trigger VMS through modulation of neurons expressing neurokinin 3 receptor (NK3R) in the median preoptic area has revolutionized our understanding of VMS pathophysiology. During oestrogen withdrawal, hyperactivated KNDy neurons release excessive levels of neurokinin B, inappropriately triggering heat dissipation responses that are characteristic of hot flushes. This mechanistic insight has enabled the development of NK3R antagonists as the first non-hormonal therapeutic specifically targeting VMS neurobiology. These new treatments offer promise for populations in which hormone therapy is contraindicated. This Review synthesizes the current understanding of VMS neurobiological pathways, examines translational approaches from preclinical animal models to clinical studies, and discusses the evolution of treatments and mechanism-based interventions that might fundamentally transform the management of menopausal symptoms. Treatments are now available that target the specific neurobiological pathways underlying vasomotor symptoms, which is an important advance in the management of menopause. This Review outlines the current understanding of these pathways, charts the translation of preclinical work to clinical studies and discusses how mechanism-based interventions have evolved.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 7","pages":"387-403"},"PeriodicalIF":39.1,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NKX6.1 expression is linked to successful pancreatic islet transplantation","authors":"Senegal Carty","doi":"10.1038/s41574-026-01255-8","DOIUrl":"10.1038/s41574-026-01255-8","url":null,"abstract":"","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 6","pages":"321-321"},"PeriodicalIF":40.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causes of sarcopenia and frailty in people taking GLP1RAs","authors":"Henning T. Langer, Aniket S. Joshi, Ursula Müller-Werdan, Kristina Norman","doi":"10.1038/s41574-026-01254-9","DOIUrl":"10.1038/s41574-026-01254-9","url":null,"abstract":"Medications based on glucagon-like peptide 1 pathways are an efficient drug treatment for people with obesity, often eliciting rapid and pronounced weight loss. However, concerns have been raised regarding accelerated muscle wasting and sarcopenia. Here, we discuss some of the latest research in this area.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 7","pages":"383-384"},"PeriodicalIF":39.1,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}