Review Articles in 2014

People with severe mental illness are at increased risk of developing diabetes mellitus. This Review examines the epidemiological association between severe mental illness and diabetes mellitus and the mechanisms underlying this association. The clinical implications of this comorbidity are also explored.

Alterations in neural-stem-cell (NSC) homeostasis can contribute to the consequences of neurodegenerative diseases, healthy ageing and tissue repair after damage. This Review discusses emerging information on the function of insulin-like growth factors (IGFs) and IGF and/or insulin receptor signalling in the context of NSC regulation. The authors also propose a model for IGF-II in which the choroid plexus is a major component of the NSC niche.

Disordered gastric emptying (also known as gastroparesis) is a complication frequently associated with long-standing type 1 diabetes mellitus and type 2 diabetes mellitus. In this Review, Phillips and colleagues discuss the underlying pathophysiology of gastroparesis in patients with diabetes mellitus. In addition, diagnosis, symptom management and emerging therapies are addressed.

During the past 15 years, our understanding of phaeochromocytoma and/or paraganglioma and the management of affected patients and their relatives have been revolutionized. Particular progress has been made in our understanding of the genetic changes underlying these tumours. This Review discusses the key advances that have occurred over this period.

Abdominal obesity is associated with an increased risk of cardiovascular disease, insulin resistance, type 2 diabetes mellitus and all-cause mortality, whereas gluteofemoral obesity has opposing associations. In this Review Fredrik Karpe and Katherine Pinnick discuss the developmental and functional differences between upper-body and lower-body fat depots and provide mechanistic insight into the disease-protective effects of lower-body fat.

In this Review, the authors discuss the clinical features of patients with sporadic pituitary adenomas that are associated withAIP or MEN1mutations, and discuss the molecular mechanisms potentially involved in pituitary adenoma tumorigenesis. They also discuss genetic screening of patients with sporadic pituitary adenomas and investigations of relatives of these patients who also have the same genetic mutations.

Collectively known as the thyroid transcription factors (TTFs), expression of NKX2-1, FOXE1, PAX8 and HHEX is essential for normal development and maintenance of the adult thyroid gland. In this Review, the authors discuss the roles of each of TTFs in the developing and adult thyroid gland, as well as in non-thyroid tissues. Mutations in the genes encoding TTFs can result in a spectrum of phenotypes, such as thyroid dysgenesis and thyroid cancer, which are also addressed.

In this Review, the authors explore the interactions between obesity, haematopoiesis and the immune system through systemic effects and changes to the primary haematopoietic environment—the bone marrow niche. They also discuss the effects of adipocytes and adiposity on haematopoietic stem cell and progenitor cell populations, with the goal of understanding how obesity might compromise the core haematopoietic system.

Despite the availability of a wide range of different dietary strategies for weight loss, unhealthy weight gain and obesity are growing problems. This Review discusses the efficacy of changes in dietary macronutrient content for healthy weight loss and weight management. The underlying causes of interindividual variations in response to the same dietary approach are also discussed and the feasibility and potential implications of personalized weight loss strategies is considered.

Branched-chain amino acid (BCAA) levels are increased in individuals with obesity and are associated with worse metabolic health and future insulin resistance. In this Review, Christopher Lynch and Sean Adams discuss whether and how impaired BCAA metabolism might occur in obesity and how perturbations in BCAA levels reflect the insulin resistant and type 2 diabetes mellitus pathophenotypes.

Stem cells have an important role in the embryogenesis and homeostasis of the adrenal gland. Walczak and Hammer discuss the molecular networks that regulate the establishment and maintenance of the stem cell population in the fetal and definitive adrenal glands and how genetic defects that perturb these pathways contribute to the development of adrenal disease.

Hypoglycaemia is a frequent adverse effect of some therapies for diabetes mellitus, and can have serious consequences. This Review describes the epidemiology of hypoglycaemia in adults with diabetes mellitus, principally in those treated with insulin. The consequences of hypoglycaemia are discussed, with particular focus on the cardiovascular and neurological morbidities that can occur.

The prevalence of obesity has increased to epidemic proportions. In the past few years, whether patients with obesity can be metabolically healthy has been debated. This Review discusses the controversy regarding metabolically healthy obesity, as well as the debate regarding the relative importance of fatness versus fitness for overall, and particularly cardiovascular, health.

Determination, differentiation and development of the gonads are important processes in early mammalian development. This article is focused on the genetic networks underlying these processes, whose disruption in humans can lead to disorders of sex development. The authors discuss the pathways controlling sex-specific gonadal development, from the bipotential gonad to the fully differentiated ovary or testis.

Mitochondria have a fundamental role in regulating metabolic pathways and in maintaining energy balance. In this Review, Carole Nasrallah and Tamas Horvath discuss the contribution of mitochondrial function, in particular mitochondrial dynamics, to central metabolism from the hypothalamic perspective and describe how mitochondrial dysfunction can lead to the development of metabolic diseases.

Although important risk factors for coronary heart disease (CHD) are well known, advances in research might facilitate improved risk stratification of patients. This Review discusses the latest developments in metabolic biomarkers of cardiovascular disease, including lipoproteins, homocysteine, calcium metabolism and glycaemic markers. It also discusses whether these biomarkers' associations with CHD are sufficient to improve current risk-stratification metrics.

Mutations in the genes that encode the thyroid hormone receptors (THRs),THRA and THRB, result in resistance to thyroid hormone disorders, RTHα and RTHβ, respectively. In this Review, the authors discuss mutations that have been identified in patients with RTH and mouse models of these disorders that have contributed to understanding the physiology and functions of THRs.

Gynaecomastia is a common condition that is generally benign. However, the condition can cause localised pain and might be the result of a serious underlying illness or medication. In this Review, the latest advances in the pathophysiology, evaluation and management of gynaecomastia are discussed.

Disorders of sex development (DSDs) arise when the tightly regulated process of sex determination in the developing bipotential gonads is disrupted. In this Review, the authors discuss mutations in sex determining genes that are associated with DSDs, as well as classification of the disorders and the psychosexual differentiation of individuals with DSDs.

The rate of osteoporotic fractures seems to be stabilizing, but is still associated with considerable disability, costs and an increased risk of mortality. This Review summarizes the evidence regarding osteoporosis-related fractures and their link with mortality and examines data on the effects of treating osteoporosis on mortality in patients with this condition.