News & Views in 2017

Three cardiovascular outcome trials failed to show superiority of DPP4 inhibitors compared with placebo in patients with type 2 diabetes mellitus and high cardiovascular risk, a rather disappointing finding. Now, a post hoc subgroup analysis suggests that patients treated with metformin at baseline might benefit from DPP4 inhibitors in contrast with metformin non-users.

In the current era of immunotherapy successes, Min and colleagues report the promising preclinical development and efficacy of a CAR T cell therapy that recognizes ICAM-1, which is highly expressed in advanced thyroid cancers. Herein, we discuss the feasibility of this approach and its implications for future therapies to treat thyroid cancer.

A recent study reports that the global prevalence of paediatric obesity increased to >5% between 1975 and 2016. This increase occurred even as the prevalence of paediatric underweight decreased slightly but remained >8%. These average prevalence changes blur the remarkable regional variations in how prevalence has changed. There is a pressing need to address both underweight and obesity worldwide.

Although the favourable effects of high-intensity resistance and impact training (HiRIT) on bone strength have been demonstrated, it is generally considered unsuitable for older adults. A recent study reports that 8 months of HiRIT was efficacious and induced no adverse effects in older postmenopausal women with, or at risk of, osteoporosis.

Rodent studies have indicated that low-carbohydrate diets prevent age-related cognitive decline and extend lifespan due to increased circulating levels of ketone bodies. A possible physiological mechanism for how ketone bodies exert this effect might be by improving central nervous system insulin resistance, which makes this finding interesting with regards to the prevention of cognitive decline and dementia in patients with type 2 diabetes mellitus.

The concept of metabolically healthy obesity (MHO) suggests that obesity might be a benign condition. This view has been challenged by a recent study demonstrating that, among 3.5 million individuals, those with MHO still have a higher risk of cardiovascular diseases than individuals who are metabolically healthy and normal weight.

A recent study has shown that evolocumab, an injectable monoclonal antibody directed against proprotein convertase subtilisin/kexin type 9 (PCSK9), robustly reduces levels of LDL cholesterol and decreases the risk of cardiovascular disease in patients with and without diabetes mellitus. When given on top of statins, evolocumab does not induce diabetes mellitus.

Two phase III trials using the selective SGLT2 inhibitor dapagliflozin or the dual SGLT2/SGLT1 inhibitor sotagliflozin in patients with type 1 diabetes mellitus show similar clinical benefit (reduction of HbA_1c, body weight, blood pressure and insulin dose). The risk of hypoglycaemia and diabetic ketoacidosis with these inhibitors can be managed by careful adjustment of insulin therapy.

The patient-centred approach to the management of hyperglycaemia, encouraged by current guidelines, requires the availability of tools to quantify the benefits and harms of intensive glucose control. Although several scores enable estimation of the long-term risk of developing diabetes-related complications, there are very few validated models to predict the risk of severe hypoglycaemia.

Romosozumab, a recently developed sclerostin inhibitor, stimulates bone formation and inhibits bone resorption, thereby markedly increasing bone mass and reducing fracture risk. But will a red flag regarding possible adverse cardiovascular events derail this promising new drug for osteoporosis?

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.

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.

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.

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.

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.

Recent reports suggest that molecular therapies targeting ANGPTL3 and its encoded protein angiopoietin-like protein 3 have clinical potential comparable to therapies targeting PCSK9 and its encoded protein proprotein convertase subtilisin/kexin type 9. By mainly affecting triglyceride-rich lipoproteins, ANGPTL3 inhibition might prove complementary to LDL cholesterol lowering with PCSK9 blockade.