Reviews & Analysis

Graves orbitopathy has a negative impact on a patient’s quality of life. This Review provides an overview of the field and outlines the optimal management of Graves orbitopathy. The authors also highlight future research questions to direct future clinical trials.

The dominant immune cell type causing pancreatic islet inflammation in individuals with obesity and/or type 2 diabetes mellitus is the macrophage. In this Review, we focus on the characteristics of inflammation in obese or type 2 diabetes mellitus islets and the consequences of this with respect to β-cell function.

Personalized, or precision, medicine in type 2 diabetes mellitus is becoming a reality with new insights into the contributions of subgroup analyses. The roadmap to future implementation must take into account individual and subgroup variability in genetic architecture, environment, clinical measures, lifestyle, cost-effectiveness and treatment burden.

Multikinase inhibitors are effective treatments for thyroid cancers, acting primarily as antiangiogenic agents. This year, advances have been made in selective targeting of RET and BRAF in patients with medullary and anaplastic thyroid cancers, respectively. However, Hürthle cell carcinomas have a unique genomic landscape with no dominant truncal drivers, precluding simplistic approaches to therapeutic targeting.

In this Review, the authors highlight findings from genome-wide association studies and studies using various omics technologies individually to identify mechanisms of osteoporosis, which is a highly heritable condition. They also summarize current studies of data integration to understand, diagnose and inform the treatment of osteoporosis.

In this Perspectives, Lean and colleagues discuss harnessing social movements to address the obesity epidemic.

This Review provides an up-to-date overview of the lipolytic effects of growth hormone (GH), setting current knowledge into the context of historical data. In addition, the molecular mechanisms of GH-induced lipolysis and insulin resistance as well as the actions of GH on different adipose tissue depots and adipocyte subsets are discussed.

This Review provides an overview of the extensive crosstalk between adipocytes, resident innate immune cells and the sympathetic nerves that innervate adipose tissue, as well as the changes that occur in these secretory and signalling pathways in obesity.

Feeding is regulated by defined neuronal pathways and circulating factors that ensure homeostatic balance is maintained. However, many emotion-affective pathways are also involved in communicating positive and negative valence on feeding behaviour. In 2019, several seminal discoveries were made that illuminate the complex interaction between homeostatic and hedonic feeding control mechanisms.

Pancreatic islets, which are critical for glucose homeostasis, are endocrine microorgans embedded in the exocrine pancreas; their location has often limited studying their function. In 2019, advances in islet biology were achieved with new technologies extending findings from several decades ago and with conceptual advances built on findings from other fields.

Bariatric surgery results in sustained weight loss and improvement in many obesity-related comorbidities. However, the effects of bariatric surgery on long-term mental health are less clear. A recent longitudinal cohort study shows that patients undergoing bariatric surgery seek mental health services at higher rates after surgery than before surgery and identifies specific risk factors for increased psychiatric service use.

Exercise is a potent modulator of intestinal microbiota composition and function. In 2019, several studies uncovered biologically important links between skeletal muscle and the gut microbiota, revealing how the gut bacteria respond to an exercise challenge and have reciprocal roles in fuel availability, muscle function and endurance performance.

Although dietary protein is crucial for human health, excessively high protein intake could have negative health consequences. This Perspective serves as a word of caution against the trend of protein-enriched diets and provides an evidence-based counterpoint that underscores the potential adverse public health consequences of high protein intake.

A cross-sectional study shows that proxies of circadian misalignment, such as late chronotype and social jet lag, are associated with increased adiposity in adolescent girls but not adolescent boys, highlighting a potential sex-specific effect of circadian misalignment. Interventions targeting sleep timing should be considered in the prevention of adolescent obesity.

In this Expert Consensus Statement, the authors define 10 key characteristics (KCs) for endocrine-disrupting chemicals. They further describe the logic by which these KCs are identified and the assays that could be used to assess several of these KCs.

Early and intensive glycaemic control protects patients with type 2 diabetes mellitus (T2DM) from the development of late cardiovascular complications. The authors of the VERIFY trial now show that a more durable attainment of HbA_1c <7% is observed by adding vildagliptin to metformin as starting therapy in newly diagnosed patients with T2DM.

A nationwide study conducted in the USA demonstrated that an intervention combining gamification with social incentives, conducted within the context of a behavioural economics platform, can result in a moderate yet significant increase in physical activity in adults with obesity over a period of 24 weeks with an additional 12 week follow-up.

Metformin is the mainstay therapy for type 2 diabetes mellitus. A new study shows that metformin acts directly on gut bacteria to elevate cAMP-induced agmatine production, thereby increasing lipid metabolism and lifespan in model organisms. These data identify links between metformin and gut microbiota that might be important for increasing longevity.

Sodium–glucose cotransporter 2 (SGLT2) inhibitors are a fairly new class of treatment for diabetes mellitus. Some data suggest SGLT2 inhibitors are associated with a risk of severe urinary tract infections. However, meta-analyses of trials and a large population-based cohort study show no increased risk, which provides important reassurance for patients and prescribers.

This Review outlines the mechanisms by which bile acids regulate glucose homeostasis and the settings in which endogenous bile acids are altered, and provides suggestions for future research.