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Extracellular danger-associated molecular patterns signal to NOD-like receptors, but the exact signalling pathways remain unclear. The inflammasomes, a subgroup of these receptors, translate danger signals into inflammatory responses by maturing IL-1 and IL-18. In 2017, researchers reported novel functions of the mutual interaction between metabolism and the inflammasomes in health and disease.
Studies of rare growth disorders taken together with large-scale genetic studies of adult height variability have uncovered a large genetic network regulating childhood growth. Advances in technology and experimental model systems will help decipher the molecular mechanisms of this complex network and lead to novel treatment approaches for growth disorders.
This Review focuses on the adverse effect of nonalcoholic fatty liver disease (NAFLD) on the risk of chronic vascular complications of diabetes mellitus. The putative pathophysiological mechanisms by which NAFLD might contribute to the development and progression of chronic vascular complications of diabetes mellitus are also discussed, and the principles of NAFLD treatment are critically evaluated.
Nutraceuticals are gaining legitimacy and their potential clinical role is expanding. Data from 2017 provides evidence for their possible use in type 2 diabetes mellitus, the metabolic syndrome, obesity, dyslipidaemia and osteoporosis. Ongoing high-quality research in this area might justify future selective implementation of nutraceuticals into general health practice.
The artificial pancreas — the automated closed-loop control of diabetes mellitus — made its first outpatient strides in 2011. In 2017, the results of long-term clinical trials on the artificial pancreas were published, the first hybrid commercial artificial pancreas system was approved and the artificial pancreas was tested under increasingly demanding conditions. Thus, artificial pancreas technology is here to stay.
The global epidemic of type 2 diabetes mellitus (T2DM) and its complications is a major threat to public health. This Review provides an updated view of the global epidemiology of T2DM and the dietary, lifestyle and other risk factors for T2DM and its complications.
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.
The incidence of adolescent obesity is increasing, which has serious long-term implications for the affected individuals and wider society. Here, Thomas Reinehr outlines the effects of adolescent obesity and discusses how the epidemic could be addressed.
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 HbA1c, 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 hypothalamus is the main integrator of endocrine regulation. Glia–neuron interactions contribute to physiological processes such as puberty, the maintenance of bodily homeostasis and ageing. Here, Vincent Prevot and Jerome Clasadonte discuss glia–neuron interactions in the control of hypothalamic neuroendocrine function.
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.
Targeting thermogenesis in brown fat and skeletal muscle to expend energy and reduce fat mass is a promising therapeutic strategy for treating obesity and related metabolic diseases. Here, Betz and Enerbäck discuss the different molecular pathways regulating thermogenesis in these organs and discuss how they can be therapeutically exploited.
Populations of African descent are at the forefront of the worldwide epidemic of type 2 diabetes mellitus (T2DM). Here, Anne Sumner and colleagues discuss issues related to the diagnosis and prevention of T2DM in these populations, including screening test efficacy, prevention strategies and the relative paucity of genomic data.
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?
