Reviews & Analysis

Typically, our mechanistic understanding about links between exercise and mortality come from epidemiological and short-period training studies. An initial transcriptomic study shows that decades-long endurance training shifts skeletal muscle gene activity to favour cellular respiration, upholding the consilience of evidence for ‘aerobic’ as a central feature of health and longevity.

Bone marrow adipose tissue secretes adipokines and is involved in glucose and lipid metabolism. The confined bone marrow cavity could partially explain the resistance of bone marrow adipose tissue to insulin-mediated glucose uptake and its role in systemic energy regulation.

Most research treats endometriosis as a single entity, potentially obscuring informative subtype-specific associations with risk factors, biomarkers and treatment responses. A 2020 study raises the hypothesis that deep endometriosis oestrogen receptor-α expression might be associated with progestin treatment and the degree of post-surgical excision pain.

For type 1 diabetes mellitus (T1DM), keeping glucose levels within the normal range of 65–150 mg/dl with administered insulin has had limited success. Now, Fussenegger and colleagues have engineered cells to release insulin in response to electrical signals, but can this advance lead to better glucose control?

Thermogenic adipose tissue is a metabolic sink for excess fuel and is a promising target for the treatment of obesity and type 2 diabetes mellitus. However, hurdles exist in activating thermogenic adipose tissue in humans. A new study developed a drug screening platform utilizing human beige adipose tissue and identified non-canonical activators.

Available interventions for adolescents with obesity are based on behavioural therapy and lifestyle modification. A new randomized, controlled trial provides evidence of efficacy of a pharmacological therapy, liraglutide, for weight control in adolescent obesity. The indications for more widespread use of this medication in clinical practice are under discussion.

Neuroendocrine liver metastases often require multiple modes of treatment to attain disease control, which can utilize various forms of radiolabelled agents either delivered systemically or preferentially towards the liver. A recent trial suggested both safety and efficacy of a novel approach of combining the two to provide a radiation ‘boost’ to hepatic deposits.

Available evidence demonstrates a crosstalk between the renin–angiotensin and the parathyroid hormone–vitamin D systems. A new study suggests that vitamin D supplementation can lower systolic blood pressure and plasma aldosterone levels in patients with primary aldosteronism.

Current recommendations for perioperative doses of hydrocortisone in patients with adrenal insufficiency undergoing major surgery with general anaesthesia have been examined in a new paper. Compared with current guidelines, lower doses of hydrocortisone, tapered quickly back to baseline levels of glucocorticoids, were found to be effective and safe.

Effective medical treatment for thyroid eye disease, a debilitating condition that can cause sight loss, has been lacking. A recent phase III trial of teprotumumab, an IGF1R antagonist, reports encouraging results and could be a game changer. Here, the trial is put in the context of current management strategies to address this question.

A new study reveals that a high-sugar diet acutely alters human sperm small RNA profiles after 1 week and that these changes are associated with changes in sperm motility. This rapid response by sperm to nutritional fluctuation raises intriguing questions regarding the underlying mechanisms and the potential effects on offspring metabolic health.

In a cross-sectional study of individuals with type 1 diabetes mellitus, those who were designated to be slow disease progressors had an increased proportion of autoreactive, islet-specific CD8⁺ T cells expressing an ‘exhausted’ phenotype. By contrast, rapid disease progressors had increased numbers of islet-specific CD8⁺ T cells with a transitional memory phenotype.

A discovery metabolomic study was performed in a large cohort of adults to identify circulating biomarkers of frailty. The study found that carnitine and vitamin E pathways were dysregulated in frail compared with non-frail participants. These findings point to dysregulated mitochondrial metabolism as a potential root of age-related frailty.

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.

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.

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.

Alternate day fasting (ADF) has gained considerable popularity as a weight loss intervention. A new study provides data showing that zero-calorie ADF (defined as 36-hour water fast alternating with 12-hour feast) is a safe and effective intervention to lower body weight and metabolic disease risk in participants who did not have obesity.