Reviews & Analysis

In this Perspectives article, Paul Zimmet and colleagues outline how current estimates of the prevalence diabetes mellitus and of related mortality are imprecise. They call for international consensus on uniform standards and criteria for reporting national data on diabetes mellitus.

In this Review, Lício Velloso and colleagues describe the main components involved in the proteostasis network and consider how defects in these components might interfere with the correct function of the hypothalamus in obesity and ageing.

This Review focuses on the diagnosis, natural history and management of children with subclinical hypothyroidism, as well as the controversy regarding treatment. The latest data on health outcomes, metabolic issues and the risk of cardiovascular disease are outlined.

Animal models of human congenital infection are needed to understand when, how and why Zika virus (ZIKV) is transmitted to the fetus. The recent development of mouse models of ZIKV placental transmission, which results in high rates of pregnancy loss, alongside fetal brain and ocular malformations, have started to unravel the mysteries of placental infection and transmission.

Several classes of glucose-lowering therapies are now available for treatment of type 2 diabetes mellitus. In this Review, the current knowledge relating to mechanisms of action, pharmacokinetics, pharmacodynamics and safety profiles is presented for members of each of these drug classes.

Gestational diabetes mellitus (GDM) is associated with considerable risks to both the mother and developing baby. In this article, the authors review the evidence from randomized controlled trials for strategies designed to prevent GDM, such as lifestyle modification, dietary supplementation and pharmacological approaches.

In this Review, Romain Barrès and Juleen Zierath outline the current understanding of the mechanisms underlying how lifestyle factors affect epigenetic changes involved in the risk of type 2 diabetes mellitus. The latest findings on the mechanisms by which diet and exercise affect the epigenome are also discussed.

In this Review, Weitzmann and Ofotokun examine the evolution of the field of osteoimmunology and how advances in our understanding of the immuno–skeletal interface might lead to novel approaches to prevent and treat bone loss, and avert fractures.

Patients with adrenoleukodystrophy have a complex, X-linked peroxisomal disease, which is characterized by the development of adrenal insufficiency, myelopathy and progressive cerebral white matter lesions. In this Review Stephan Kemp and colleagues discuss the clinical presentation, natural history, diagnosis and treatment of this disease.

Despite effective treatments for pituitary tumours, chronic syndromes can occur in patients during long-term follow-up. This Review describes these syndromes, which result from the effects of the initial disease, such as hormonal excess or pituitary insufficiency, and the effects of treatment modalities.

Susceptibility to impaired metabolic health in relation to obesity is not necessarily mediated by overall fatness, but is largely dependent on the distribution of body fat and the ability to sufficiently expand adipose tissue depots. A recent study published in Diabetes provides genetic evidence to support the concept of a 'metabolically healthy obese' phenotype.

The sequenced genomes of individuals aged ≥80 years, who were highly educated, self-referred volunteers and with no self-reported chronic diseases were compared to young controls. In these data, healthy ageing is a distinct phenotype from exceptional longevity and genetic factors that protect against disease might be enriched in this population.

Here, Mark Tarnopolsky and colleagues propose that the systemic benefits of exercise are mediated by exosomes containing peptides and nucleic acids (exerkines) that act in an autocrine, paracrine and/or endocrine manner. They also discuss the therapeutic potential of using exerkine-enriched native or modified exosomes to treat metabolic diseases such as obesity and type 2 diabetes mellitus.

Osteocytes have a central role in bone homeostasis, integrating the effects of mechanical and hormonal stimuli on bone. Here, Lilian Plotkin and Teresita Bellido discuss the potential of osteocytic signalling pathways as therapeutic targets to improve bone health and maintain musculoskeletal integrity.

In a new estimate, the global incidence of diabetes mellitus has quadrupled since 1980 and now affects nearly as many individuals as the 'Spanish flu' pandemic of the early 20^th century. With such an increasing burden on healthcare systems, what can be done to limit the devastating impact of this disease?

An elaborate neural network integrating many internal homeostatic and external signals governs the onset of puberty and subsequent fertility. Here, Allan Herbison provides an update on the morphology and function of the gonadotropin-releasing hormone neurons, focusing on their role in the onset of puberty and fertility.

Activation of AMP-activated protein kinase (AMPK) is dependent on adenosine nucleotides levels in the cell, which vary according to the energy status; AMPK is therefore described as an energy sensor. This Review discusses the role of hypothalamic AMPK in controlling energy balance, and how this knowledge might be used to develop new antiobesity drugs.

In this Review, screening and treatment recommendations are compared for familial hypercholesterolaemia, familial combined hyperlipidaemia and elevated lipoprotein(a); common, inherited disorders of lipoprotein metabolism that are associated with atherosclerotic cardiovascular disease. New treatments are considered alongside established therapeutic strategies.

The NADPH oxidase family of enzymes produce hydrogen peroxide (H₂O₂), a critical substrate for thyroid hormone synthesis. However, H₂O₂is also a potent oxidant that can cause DNA damage, which might lead to thyroid carcinogenesis. Here, the authors discuss the physiological attributes of thyroid NADPH oxidases and their pathological involvement in thyroid cancer.

Rapid, minimally invasive control of explicit neural activity would be a major advance for basic and clinical research in the neuroscience and neuroendocrinology fields, and could have applications for the potential treatment of neurological disorders. A new study by Stanley et al. brings us closer to this goal.