Comment in 2025

Neurodegeneration is not merely determined by local cues but is also influenced by systemic signals, such as factors released by peripheral tissues. Muscle-to-brain communication via muscle-secreted signalling factors is increasingly recognized as an important signalling axis. Collectively, muscle-to-brain signalling could be harnessed to impede neurodegeneration and delay cognitive decline during ageing.

FDA approval of the selective HIF2α inhibitor belzutifan for advanced phaeochromocytoma and paraganglioma (PPGL) is an important milestone in precision oncology. This achievement underscores the power of scientific collaboration in establishing HIF2α as a central driver of PPGL pathogenesis and offers hope for a historically underserved group of patients.

Future treatment targets for type 1 diabetes mellitus will be truly normal blood levels of glucose with a minimum of exogenous insulin and no hypoglycaemia. Here, we present some of the landmark trials from the past 20 years that are driving progress to that goal.

Molecular biology and omics-based approaches over the past 20 years have rapidly advanced the discipline of exercise metabolism. Here, we examine three innovative human metabolic studies that have increased our understanding of exercise’s complex molecular landscape in skeletal muscle and beyond, and highlight key future directions.

Aside from a few days around Halloween, the skeleton tends not to have a positive image. However, at least in the biomedical field, this view is changing as bone is now identified as an endocrine organ that positively regulates a broad range of key functions, including several aspects of energy metabolism.

Thyroid cancer management has evolved from a uniform, surgery-centric approach to a paradigm of precise diagnosis and personalized therapy. Transformative advances have occurred in the past two decades; however, global inequities in accessing these innovations are a key challenge.

Over the past two decades, polycystic ovary syndrome (PCOS) has been redefined from a symptom-based condition to a biologically complex disorder with distinct genetic, developmental and phenotypic features. Translating these advances into precision diagnostics, early interventions and equitable care is essential to improve outcomes.

Over the past 20 years, obesity research has resulted in a better understanding of the complex disease mechanisms underlying the condition, including biological, behavioural, societal and environmental factors. Although obesity research in the past 10 years has resulted in very effective and safe obesity treatments, more research is needed to improve the lives of people with obesity.

Immediate attention is paramount for addressing the escalating prevalence of severe insulin resistance during pregnancy. A collaborative and multidisciplinary approach involving clinical care, public health initiatives and advanced technologies is essential for enhancing care, improving maternal and fetal outcomes, and mitigating long-term metabolic risks.

Imaging has a growing role in the evaluation of obesity-related disorders and the effects of weight loss, especially given the increasing use of glucagon-like peptide 1 agonists. New imaging biomarkers are emerging. Artificial intelligence applications for automated quantification of body composition underline future capabilities of whole-body MRI to comprehensively assess patients with obesity.

Rapid weight loss with GLP1 receptor agonists can come at the cost of skeletal muscle, potentially undermining metabolic and functional outcomes. This Comment highlights emerging evidence and advocates for clinical strategies that prioritize muscle preservation to ensure the long-term success and safety of pharmacological weight management.

As healthcare professionals, scientists and educators, our intent is to empower people affected by diabetes mellitus; however, if our language is stigmatizing, our impact might be disempowerment. If we do not choose our words with care, we risk undermining the very autonomy we seek to promote.

Adult-onset type 1 diabetes mellitus differs from the early onset form in terms of residual endogenous insulin secretion, comorbidities and baseline cardiorenal risk. Adjunct therapy with glucagon-like peptide 1 receptor agonists could offer benefits in this population of patients by preserving β-cell mass and function while also contributing to cardiorenal risk mitigation.

Obesity-related subfertility is an increasingly recognized concern. Pharmacotherapies (particularly glucagon-like peptide 1 receptor agonists and combination therapies), alongside lifestyle intervention, enable meaningful and sustainable weight loss in people with and without type 2 diabetes mellitus. Weight loss can benefit sperm parameters, but the optimal amount and rate of weight loss requires further study.

Precision nutrition is often used interchangeably with personalized nutrition, creating confusion and limiting progress. This Comment proposes a working definition of precision nutrition, outlines enabling frameworks such as artificial intelligence and highlights the need for consistent research standards and clinical validation to support and maximize precision nutrition’s potential in healthcare.

Body mass index (BMI), as its name indicates, is a marker of total body mass and not a specific marker of adipose tissue mass. Here, we position relative fat mass (RFM) as an ideal alternative to BMI by highlighting the superior performance of RFM in assessing cardiometabolic risk.

The growing population of older adults with type 1 diabetes mellitus presents unique challenges, including frailty, comorbidities and polypharmacy. A holistic multidisciplinary approach is crucial to address this population’s complex needs, improve care delivery, and ensure their independence and quality of life amid the realities of ageing with this lifelong condition.

Over the past decade, academies have emerged as transformative platforms, bridging traditional PhD programmes and professional development. By supporting PhD students and postdoctoral researchers, they foster interdisciplinary collaborations, build resilient research communities and sustain global scientific talent to address complex challenges in endocrinology, metabolism, neurology, data science and beyond.

Anti-PIT1 hypophysitis is a form of paraneoplastic autoimmune hypophysitis. The condition is attributable to the ectopic expression of pituitary-specific positive transcription factor 1 (PIT1) in tumour tissues, which leads to autoimmunity against PIT1-positive anterior pituitary cells. In the past few years, it has been reported that anti-PIT1 hypophysitis can occur as an immune checkpoint inhibitor-related hypophysitis.

Pituitary neuroendocrine tumours (PitNETs) exhibit notable sex-related differences, particularly in prolactinomas and corticotroph tumours. Findings from the past 5 years in other cancers suggest that interactions between sex hormones and the immune system, as well as epigenetic modifications specific to sex chromosomes, could influence sex differences in tumour development.