Articles in 2015

Antisense oligonucleotides have proven effective at preventing protein synthesis as a result of their on-target specificity. Recent data from several clinical trials including a phase I trial targeting Lp(a), published in The Lancet, highlight the therapeutic potential of antisense oligonucleotides in regulating plasma lipid levels.

Our understanding of bone biology and the subsequent development of therapies to treat bone diseases have both expanded greatly in the past 30 years. This article reviews some of the key advances made in these fields during the past decade.

Over the past decade, the growing epidemic of type 2 diabetes mellitus (T2DM) and its associated complications has presented both challenges and opportunities. Progress has been made in incretin-based therapies, bariatric surgeries and inhibiting renal glucose reabsorption; however, long-term safety and efficacy studies are required. Advances in the prevention of macrovascular complications of T2DM from ongoing clinical trials are expected soon.

Long-chain acylcarnitines (LCACs) are widely used as diagnostic markers in several metabolic disorders; however, research into the potential effects of excessive accumulation of LCACs or the roles of acylcarnitines as physiological modulators of cell metabolism is lacking. This Review, therefore, aims to provide a theoretical framework for the potential consequences of tissue build-up of LCACs among individuals with metabolic disorders.

Parathyroid hormone/parathyroid hormone-related peptide receptor (PTHR1) is a family B G-protein-coupled receptor and is involved in the regulation of skeletal development, bone turnover and mineral ion homeostasis. This Review discusses fundamental aspects of ligand-binding and signalling mechanisms at PTHR1, highlighting the relationship between ligand structural modification and variation in PTHR1 signalling responses. The action of these signalling mechanisms in disease states in which PTHR1 function has an important role are also discussed.

In a new study published in The Lancet Diabetes & Endocrinology, metformin use is associated with significantly increased all-cause mortality in patients with type 2 diabetes mellitus and stage 5 chronic kidney disease (CKD). The findings support current recommendations that metformin should not be used in patients with stage 5 CKD.

In a new trial, provision of antenatal dietary and lifestyle advice to pregnant women who are obese is associated with modest improvements in maternal diet. This intervention is, however, inadequate to affect pregnancy and birth outcomes, and challenges the notion that limiting gestational weight gain can improve pregnancy outcomes.

For individuals with diabetes mellitus, the lifetime risk of developing a foot ulcer can be as high as 25%, but these complications are preventable. Here, Bowling and colleagues discuss the mechanisms that lead to foot ulcers in patients with diabetes mellitus. The authors emphasise the need for a multidisciplinary management strategy to prevent and treat diabetic foot complications.

Paget's disease is a disorder of bone that manifests in one or several bones and is initiated by osteoclast-induced osteolytic lesions. In addition to a genetic cause, environmental factors, including measles virus, have been proposed to have a role in the pathogenesis of Paget's disease. Here, Frederick R. Singer discusses the present knowledge and controversies surrounding the aetiology of Paget's disease.

A recent study shows that preceding teriparatide treatment with 2 years of denosumab treatment leads to lower BMD after 4 years than either administering these interventions in the opposite order or combining them initially. However, BMD measurements could be biased in favour of using teriparatide first, owing to the time required for completion of secondary mineralization.

Liraglutide is an agonist of glucagon-like receptor-1, which is a component of an important biological system that inhibits food intake and enhances insulin secretion from the pancreas in the presence of glucose. This drug can therefore facilitate weight loss and glucose control at the same time.

Fatty acid-binding proteins (FABPs) improve the solubility of fatty acids. Here, Hotamisligil and Bernlohr describe the structure and function of FABPs in the control of fatty acid metabolism and obesity. The authors focus on FABP4 and FABP5, the most abundant FABPs in adipose tissue, and discuss how targeting these proteins might be exploited to treat metabolic diseases.

Short-chain fatty acids (SCFA) are produced by the gut microbiota from indigestible food stuffs, and might have beneficial effects on metabolism and insulin sensitivity. Here, Canfora and colleagues discuss how SCFA can modulate energy homeostasis and metabolism in adipose tissue, muscle and the liver. The authors also discuss whether SCFA might be used to modulate glucose homeostasis in humans.