Population-based incidence data on young-adult-onset type 1 diabetes and type 2 diabetes are limited. We aimed to examine secular trends in the incidence of diagnosed type 1 diabetes and type 2 diabetes with an age of onset between 15 and 39 years.

Despite the diverse nature of obesity, there is compelling genetic, clinical, and experimental evidence that endorses the important contribution of brain circuits to this condition. The hypothalamus contains major regulatory circuits for bodyweight homoeostasis, the deregulation of which can lead to obesity. Although functional perturbation of hypothalamic pathways could lie at the basis of common forms of obesity, the term hypothalamic obesity has been created to define those rare forms of severe obesity where a clear hypothalamic substrate can be identified, either of genetic or acquired origin. An in-depth understanding of the pathogenesis, clinical presentation, and therapeutic targets of hypothalamic obesity relies on the comprehension of the physiological basis of hypothalamic pathways governing bodyweight control, the mechanisms (either genetic or acquired) whereby they are perturbed, and the consequences of such perturbation. In this Review, we provide a synoptic overview of hypothalamic obesity, from basic mechanisms to clinical perspectives, with a major focus on current developments and new avenues for the diagnosis and precise treatment of these rare forms of obesity.

Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, has been shown to reduce hunger and weight in patients aged 6 years and older with proopiomelanocortin (POMC) deficiency (including biallelic variants in proprotein convertase subtilisin/kexin type 1 [PCSK1]), leptin receptor (LEPR) deficiency, or Bardet-Biedl syndrome (BBS). No approved therapies for patients younger than 6 years old currently exist. The phase 3, open-label VENTURE trial aimed to evaluate the efficacy and safety of setmelanotide in patients aged 2-5 years with POMC or LEPR deficiency or BBS.

Morbidities related to obesity are usually associated with its severity and duration. Yet, the onset of serious morbidities in early adulthood among otherwise healthy adolescents with obesity is understudied. We aimed to investigate the association between adolescent BMI and serious morbidities before age 25 years.

The promotion of continuous glucose monitoring (CGM) to standard of care for type 1 diabetes and insulin-treated type 2 diabetes reflects a robust and wide evidence base for the technology's effectiveness supported by real-world efficacy data. Multiple CGM devices are available worldwide and are marketed, in part, based on accuracy data. In this Viewpoint, we argue that accuracy metrics are no longer a point of difference between CGM devices as almost all exceed an acceptable threshold. We also argue that domains of standardisation, clinical outcomes, and sustainability should now be given primacy as CGM devices seek to be implemented for new indications. These domains are key for the success of the next generation of CGM devices. Additionally, we discuss the need to address inequalities in accessing clinically impactful technologies.

Findings from the Women's Health Initiative studies led to menopausal hormone therapy (MHT) guidelines generally recommending the initiation of MHT be limited to women within 10 years of their menopause or before the age of 60 years. This recommendation has led to women who experience troublesome menopausal symptoms and who have not commenced MHT within these limits often being denied this type of therapy. Similarly, the majority of women who might benefit from the protective effects of MHT against bone loss and fracture are not offered this treatment option if they do not fit with these criteria. Based on review of the evidence that led to the conditional initiation of MHT, and subsequent studies, we propose that the recommendations regarding the initiation of MHT need to change to be more inclusive of women outside these chronological limits.

Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder characterised by extremely high concentrations of LDL cholesterol, leading to early-onset atherosclerosis. Lomitapide is an orally administered microsomal triglyceride transfer protein (MTP) inhibitor that effectively lowers LDL cholesterol and is approved for adults with HoFH. We aimed to investigate the efficacy and safety of lomitapide in paediatric patients with HoFH receiving standard-of-care lipid-lowering therapy.

Younger-onset type 2 diabetes is associated with accelerated complications. We assessed whether complications and mortality rates differed for younger age compared with older age at diagnosis over 30 years of follow-up.

The subjective experiences of individuals living with diabetes is commonly assessed with patient-reported outcomes (PROs; eg, depression symptoms, wellbeing, health-related quality of life [HRQOL], and diabetes-related distress). Cluster analyses have identified novel diabetes subtypes differing in phenotypic and metabolic characteristics. We aimed to investigate associations between these subtypes and PROs and whether subtype predicted PROs 5 years later.