Reviews & Analysis

2014 was a good year for developments in automated insulin delivery systems for patients with diabetes mellitus. Clinical trials shifted from research units to the outpatient setting, included both adult and adolescent individuals and were conducted over periods from overnight to 24 h, with improvements seen in time spent in the target glycaemic range and reduced risk of hypoglycaemia.

Observational studies suggest that statin treatment has a fracture-preventive effect; however, there is only limited supporting evidence from randomized controlled trials. Now, results from the JUPITER trial show that rosuvastatin treatment does not reduce the risk of fractures and, further, that levels of high sensitivity C-reactive protein are not associated with fracture risk.

In 2014, many articles focusing on pituitary tumours were published, including studies on genetics, surgery, radiotherapy and medical treatment. This commentary highlights advances in the management of patients with acromegaly, Cushing disease and TSH-secreting tumours. Together, these advances will benefit the care and management of patients with pituitary tumours.

2014 has seen advances in our understanding of benign and malignant tumours of the adrenal cortex, particularly in Cushing syndrome. Modern genetics has generated a flurry of data. The challenge is to give sense to them; however, the difficulties of collecting the clinical data must not be underestimated.

In 2014, numerous noteworthy papers focusing on adipose tissue physiology were published. Many of these articles showed the promise of adipose-tissue-targeted approaches for therapeutic intervention in obesity and type 2 diabetes mellitus. Here, we highlight advances in the development and maintenance of brown and/or beige adipocytes and the metabolic implications of inflammation in adipose tissues.

Aromatase inhibitors are the most effective agents for preventing breast cancer; however, their use is associated with bone loss and an increased risk of fractures. Sestak and colleagues show that administration of an oral bisphosphonate prevents aromatase-inhibitor-induced bone loss in postmenopausal women with osteopenia or osteoporosis who are at high risk of breast cancer.

In 2014, two phase II clinical studies reported rapid, impressive increases in BMD in women with low bone mass who were treated with sclerostin inhibitors for 1 year. The antifracture efficacy and tolerability of these new, bone-building therapies are currently being investigated in phase III clinical trials.

Studies published in 2014 have helped in our understanding of the epigenetic mechanisms by which suboptimal nutritional exposures during in utero development are transmitted to subsequent generations through the maternal and the paternal germlines. Advances include identification of common genetic loci that are vulnerable to the effects of in utero undernutrition and overnutrition, as well as those that are epigenetically modified tissue-wide.

Colonization of an infant with their microbiota in early life is important for normal development of host metabolism. In this Perspectives article, Cox and Blaser posit that exposure to antibiotics that disrupt either vertical transmission or colonization and maturation of the microbiota in the infant can lead to adverse consequences such as obesity in adulthood.

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.