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.

A landmark article by The Cancer Genome Atlas Research network describes the genetic landscape of papillary thyroid carcinoma (PTC). This study identifies oncogenic driver lesions, highlights molecular pathways that drive cancer formation and defines clinically relevant disease subtypes. These findings have far-reaching implications with respect to molecular diagnosis and targeted therapies for PTC.

Vitamin D deficiency is a global health concern, which might affect the pathogenesis of diabetes mellitus. Previous studies suggest vitamin D has some potential in the treatment of type 2 diabetes mellitus. A new combined genetic study and meta-analysis reveals conflicting results regarding the effects of circulating levels of vitamin D on type 2 diabetes mellitus risk.

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.

Familial hypercholesterolaemia is caused by mutations in genes that code for proteins involved in cholesterol metabolism. Patients heterozygous for mutations in LDLR respond to statin treatment, whereas individuals with homozygous LDLR mutations do not. PCSK9 inhibitors have been developed for treating familial hypercholesterolaemia, and results are promising for patients with either heterozygous or homozygous familial hypercholesterolaemia.

Numerous studies have evaluated the use of low-dose aspirin (LDA) to reduce rates of pre-eclampsia and adverse perinatal outcomes in women considered at risk of pre-eclampsia. A new study recommends that these women should receive LDA after 12 weeks of gestation to reduce the rates of pre-eclampsia, preterm birth and fetal growth restriction.

Endocrine and metabolic pathways are a rich ground in which to examine the prognostic significance of biomarkers of cardiovascular risk. Whereas numerous biomarkers for prediction of cardiovascular disease have emerged in the past decade, far fewer have transitioned into clinical practice. Will growth hormone fulfill its potential?

The race to generate β cells from stem cells has taken another big turn. We can already generate definitive endoderm from human embryonic stem cells and functional insulin-producing cells from transplanted pancreatic progenitors. Now, differentiating glucose-responsive insulin-producing cells in vitro that function like adult human β cells has been achieved.

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.

The treatment of patients with acromegaly has progressed to encompass multimodal strategies that can include selective transsphenoidal adenomectomy, radiotherapy and somatostatin analogues. As a result, disease control and survival of these patients has improved.

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.