Reviews & Analysis

The effects of the gut microbiota on human health are tremendous. Now, a study on the microbiota of wild mice sheds light on how the microorganisms that inhabit the gut between birth and weaning determine resistance to weight gain during adulthood.

A new paper reports that the protein isthmin 1 is secreted by mature adipocytes and triggers a signalling cascade similar to that of insulin. The novel adipokine acts through an unidentified receptor tyrosine kinase and, at pharmacological doses in mice, isthmin 1 ameliorates metabolic disturbances associated with type 2 diabetes mellitus, including hyperglycaemia and liver steatosis.

Immune checkpoint inhibitor therapies induce potent anti-tumour immunity as well as immune-related adverse events that manifest as autoimmune disease — particularly thyroiditis. Translational studies and preclinical models are beginning to unravel the molecular processes that mediate these adverse events; this knowledge might enable the development of ICIs with anti-tumour efficacy and improved safety margins.

Adipose tissue macrophages (ATMs) have important roles in the regulation of inflammatory responses and insulin resistance in obesity. A new study reports that a subpopulation of ATMs, TIM4⁺ resident ATMs, modulate adipocyte size via platelet-derived growth factor-CC production during development and diet-induced adipose tissue expansion.

Pancreatic β-cell dysfunction contributes to type 2 diabetes mellitus (T2DM) pathogenesis. However, human islet studies have revealed few consistent molecular changes in T2DM, owing partly to technical and biological confounding factors. A new multi-omics study of islets from well-phenotyped living donors attempts to overcome these limitations to catalogue T2DM-associated molecular changes.

Harnessing the thermogenic, energy-expending capacity of adipocytes has the potential to combat metabolic disorders. Although β₃-adrenergic receptor agonists are the best-known activators of thermogenesis, they carry considerable cardiovascular risks. A new study demonstrates the ability of G protein-coupled receptor 3 to intrinsically drive adipose thermogenesis independent of β₃-adrenergic receptor signalling.

Metabolically healthy obesity (MHO) describes the presence of obesity with limited or no features of poor metabolic health. MHO might be a transient state associated with long-term health complications. A recent study highlights that MHO is associated with an increased risk of heart failure. Obesity, in all forms, requires intervention.

A new study has reported genetic evidence that MEK–ERK signalling is needed by β-cells, both for maintenance of β-cell mass and for optimization of insulin release. Their results point towards a new challenge of disentangling ERK signalling across multiple time scales.

A new study investigates brown adipose tissue (BAT) volume in young, metabolically healthy adults. The focus is on the associations between BAT volume and BMI, waist circumference, whole-body adipose tissue mass, visceral adipose tissue mass and cold-induced BAT activity. Of note, the reported associations differed in men and women.

COVID-19 has been described as a syndemic of COVID-19 and chronic diseases. Obesity has been identified as a contributing factor to morbidity and mortality associated with COVID-19; however, sedentary behaviours and lack of physical activity should also be targeted by health authorities to reduce the risk of severe COVID-19 outcomes.

The poor prognosis in patients with diabetes mellitus who contract COVID-19 urged physicians to question routine drug treatment for people with type 2 diabetes mellitus. What treatment should we prioritize? So far only observational studies are available, although complementary interventional studies are needed to address this issue.

Exercise training can induce robust changes in mitochondria that are beneficial for a range of metabolic health outcomes. However, a recent study suggests there might be an upper limit to the amount of high-intensity training that can be tolerated before disruptions to mitochondrial function and whole-body metabolic homeostasis occur.

Limited pharmacological treatments for uterine leiomyomata (fibroids) are available. Now, two phase III trials lasting 24 weeks showed marked reduction in leiomyoma-related heavy menstrual bleeding with relugolix, a new orally active gonadotropin-releasing hormone antagonist with add-back oestrogen (to limit bone loss) and progestin (to limit endometrial changes from unopposed oestrogen).

It is commonly accepted that dietary habits and cardiometabolic disorders are connected to the composition of the gut microbiota. However, can we really generalize and predict health by screening faecal microorganisms? A study has taken the plunge and identified a vast range of correlations supporting this possibility.

Complex phenotypic and genetic clustering of individuals who are potentially at increased risk of type 2 diabetes mellitus (T2DM) can enable the identification of individuals who are likely to develop T2DM and vascular complications. Precision medicine for prediabetes should improve prevention programmes and reduce mortality.

It is well established that marketing of unhealthy food is highly prevalent and has a detrimental effect on children’s eating behaviours and diet. A new study highlights how a new type of social media influencer — children themselves — is contributing to this phenomenon.

U-shaped or J-shaped relationships have been demonstrated between BMI and all-cause or cardiovascular mortality. Now, a study has demonstrated the correlation of increased waist circumference, high adipose tissue mass and low adipose tissue-free mass with all-cause and cardiovascular mortality in an Asian population.

In two phase III trials, surufatinib, a novel oral tyrosine kinase inhibitor targeting immune cells and angiogenesis, was effective for treating pancreatic and extra-pancreatic neuroendocrine tumours. These findings further expand the therapeutic options for patients with gastro–entero–pancreatic, thymic and lung neuroendocrine tumours.

A large fraction of patients with diabetes mellitus require insulin treatment to control glucose metabolism; however, this treatment brings risks of hypoglycaemia and provides suboptimal metabolic control. Transplantation of stem cell-derived pancreatic islet cells could be an ideal solution, which is approaching clinical translation.

A need exists for rapid, cheap and noninvasive diagnostic tests for type 2 diabetes mellitus (T2DM). Now, a smartphone-based photoplethysmography screening test has been reported to detect T2DM based on a novel digital vascular biomarker, distinct from blood glucose, analysed with deep learning.