Volume 12 Issue 12, December 2016

Treatment of type 2 diabetes mellitus with GLP1 receptor agonists can result in long-term glycaemic control or can fail over time, in which case insulin can be used as an alternative or as an additive treatment. New research shows that the latter is more likely to achieve glycaemic targets than the former.

In a recent study by Cosman and colleagues, romosozumab — a humanized monoclonal antibody targeting sclerostin — is shown to reduce the risk of vertebral and clinical fractures at 12 months compared with placebo. However, the low fracture risk of study participants necessitates the completion of an on-going clinical trial before romosozumab can be fully adopted into clinical practice.

In the Steno-2 trial, 160 individuals with type 2 diabetes mellitus, mostly in their 50s, were randomly assigned to multifactorial interventions or conventional care. Whereas microvascular and macrovascular complications were reduced during the 7.8 years of the trial period with intensive therapy, the observational follow-up data at 13.3 years and, now, 21 years demonstrate a benefit on mortality.

In this Review, Heiko Lickert and colleagues discuss β-cell heterogeneity, placing a particular emphasis on the role of islet architecture in defining phenotypic and functional plasticity among β cells. The potential to exploit β-cell heterogeneity and plasticity for diagnostic and therapeutic purposes in the context of regenerative therapies for diabetes mellitus is also discussed.

Hepatic steatosis is prevalent in individuals with obesity and is a risk factor for type 2 diabetes mellitus. In this Review, the authors discuss the disruption of endoplasmic reticulum function in hepatic steatosis and how cellular stress responses to lipid accumulation can promote or inhibit progression to severe liver pathologies.

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.