Reviews & Analysis

As not all individuals with obesity respond to lifestyle modification, pharmacotherapy has a key role in tackling the obesity epidemic. Here, Gitanjali Srivastava and Caroline Apovian review the six currently available FDA-approved anti-obesity drugs in terms of safety, efficacy and clinical utility.

A recent report found mutations in the de novo kynurenine pathway and reduced plasma levels of NAD in patients with congenital malformations. In a mouse model, the mutation not only altered the phenotype of the litters but the combination of a homozygous mutation and a niacin-free diet resulted in miscarriages.

The first large-scale, multicentric analysis of long-term results with Gamma Knife (Elekta) radiosurgery in the therapeutically challenging area of Cushing disease shows that, in selected patients, this radiation technique enables hormonal control to be achieved in most patients with relatively few adverse effects but with a significant risk of disease recurrence.

Angiopoietin-like 3 (ANGPTL3) has emerged as an important regulator of plasma lipoprotein levels by its inhibition of the enzyme lipoprotein lipase. Here, Sander Kersten provides an overview of the role of ANGPTL3 in lipoprotein metabolism and discusses why it holds considerable promise as a target for atherosclerosis.

In this Review, Elizabeth Lawson discusses the data that link oxytocin to eating behaviour and metabolism in humans. Although further investigation is required, Lawson suggests that the pathways involving oxytocin can be targeted in the treatment of metabolic diseases such as obesity and diabetes mellitus.

Household dust contaminated with common flame retardants used in everyday household items has been found to be associated with increased risk of developing smaller, as well as more aggressive forms of papillary thyroid cancer in humans. These findings emphasize the need to consider the exposome when evaluating the increased incidence of thyroid cancer.

Dementia is a complication associated with diabetes mellitus. Evidence suggests that patients with diabetes mellitus who have dementia have a unique form of the disease, albeit with similarities to vascular dementia. A recent study by Juraj Secnik and colleagues confirms this suggestion and provides insights into the clinical characteristics and treatment of the disorder.

Results from the Reducing with Metformin Vascular Adverse Lesions (REMOVAL) study show for the first time that metformin has a cardiovascular benefit in patients with type 1 diabetes mellitus (T1DM), although the benefit was limited to tertiary outcomes and was modest. Additional measures are therefore needed to reduce cardiovascular disease in patients with T1DM.

In this Opinion article, Klose and Feldt-Rasmussen posit that the true risk and disease burden of hypopituitarism after traumatic brain injury might have been overestimated in recent years. Possible reasons for this overestimation are discussed, along with current recommendations for diagnosing and treating the condition.

The clinical and metabolic heterogeneity of adult-onset autoimmune diabetes, which encompasses a spectrum of phenotypes, ranging from classic adult-onset type 1 diabetes mellitus to latent autoimmune diabetes in adults, represents a considerable challenge for the management of this disease. In this Review, the authors summarize the definition, pathophysiology and clinical features of adult-onset autoimmune diabetes and discuss their implications for treatment.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by hypercalcaemia and elevated or inappropriately normal serum levels of parathyroid hormone. Here, Walker and Silverberg review the pathogenesis, diagnosis and management of PHPT, focusing on recent advances in the field.

Whether obesity is a cause of type 2 diabetes mellitus and coronary heart disease or a shared risk factor has been an enduring subject of debate. Lyall and colleagues have used Mendelian randomization to conclude that there is a causal relationship between obesity and cardiometabolic disease. However, the analyses fail key inherent assumptions. The article does not negate a large body of data indicating that insulin resistance is the primary mechanism driving the progression of cardiometabolic disease.

Glucocorticoids are essential for adaptation to stressors (allostasis) and in maladaptation resulting from allostatic load and overload. Here, Bruce McEwen and colleagues discuss the mechanisms of glucocorticoid action in the brain and review how glucocorticoids interact with stress mediators.

In addition to controlling cellular lipid metabolism and homeostasis, sterol regulatory element-binding proteins (SREBPs) act as nodes of convergence and divergence within myriad physiological and pathophysiological processes. Here, Shimano and Sato provide a comprehensive overview of the role of SREBPs in health and disease, at the cell, organ and organism levels.

A recent randomized controlled trial has shown that patients with type 1 diabetes mellitus who are treated with multiple daily insulin injections and continuous glucose monitoring (CGM) enjoy a further improvement in glycaemic control when switched to insulin pump therapy with CGM. However, some increase in biochemical hypoglycaemia was evident with pump treatment.

Adipose tissue inflammation is an adaptive response to overnutrition in the early stages of obesity, but later becomes maladaptive. Here, Reilly and Saltiel review the cellular and molecular mechanisms of obesity-induced inflammation in adipose tissue and discuss potential therapeutic approaches.

The osteosarcoma genome has long been known to be complex, with few common features between tumours. However, a growing number of somatic genome studies, including a recent study by Behjati et al., have identified common themes in subsets of these cancers. The data suggest that subsets of somatic signatures could be therapeutically tractable targets.

A new population-based observational cohort study involving more than 1.2 million live births highlights the increased risk of congenital anomalies with increasing degrees of maternal overweight and obesity. However, by only considering data on live-born infants, the full impact of maternal overweight and obesity on this aspect of reproductive and child health is underestimated.

Thyroid dysfunction is associated with adverse obstetric and child development outcomes. Here, Tim Korevaar and colleagues put studies from the past decade on reference ranges, thyroid dysfunction determinants, adverse outcome risks and treatment options into perspective.

The balance of catabolic and anabolic glucose fluxes in the liver is crucial for glucose homeostasis and is disturbed in diabetes mellitus. In this Review, the authors discuss progress in our understanding of the regulation of hepatic glucose metabolism and highlight potential therapeutic targets for decreasing hepatic glucose production in T2DM, including lipid-induced hepatic insulin resistance, hyperglucagonaemia and excessive adipose lipolysis.