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  • News & Views |

    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.

    • Lauren Gerard Koch
    •  & Steven Loyal Britton
  • News & Views |

    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.

    • Wei Shen
    •  & Steven B. Heymsfield
  • News & Views |

    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.

    • Amy L. Shafrir
    •  & Stacey A. Missmer
  • News & Views |

    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?

    • Gordon C. Weir
  • News & Views |

    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.

    • Anthony R. P. Verkerke
    •  & Shingo Kajimura
  • News & Views |

    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.

    • Roya Kelishadi
  • News & Views |

    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.

    • Andrea Frilling
    •  & Ashley Kieran Clift
  • News & Views |

    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.

    • Gian Paolo Rossi
    •  & Livia Lenzini
  • News & Views |

    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.

    • Robert J. Weil
  • News & Views |

    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.

    • Marian Ludgate
  • News & Views |

    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.

    • Ying Zhang
    •  & Qi Chen
  • News & Views |

    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.

    • F. Susan Wong
    •  & Li Wen
  • News & Views |

    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.

    • Luigi Ferrucci
    •  & Marta Zampino
  • News & Views |

    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.

    • Sanjeev Sockalingam
  • News & Views |

    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.

    • Jingyi Qian
    •  & Frank A. J. L. Scheer
  • News & Views |

    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 HbA1c <7% is observed by adding vildagliptin to metformin as starting therapy in newly diagnosed patients with T2DM.

    • Francesco Prattichizzo
    • , Lucia La Sala
    •  & Antonio Ceriello
  • News & Views |

    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.

    • John M. Jakicic
    •  & Renee J. Rogers
  • News & Views |

    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.

    • Lesley T. MacNeil
    • , Jonathan D. Schertzer
    •  & Gregory R. Steinberg
  • News & Views |

    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.

    • John Wilding
  • News & Views |

    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.

    • Krista A. Varady
    •  & Kelsey Gabel
  • News & Views |

    A study in Danish adults over the period 1997–2016 reports a 50% reduction in thyrotoxicosis caused by multinodular toxic goiter, solitary toxic adenoma or Graves disease after the introduction of mandatory salt iodization. During the same period, there was no significant increase in overt hypothyroidism.

    • Michael B. Zimmermann
  • News & Views |

    A large registry-based study found that maternal overweight and obesity are associated with incident type 2 diabetes mellitus in offspring. The results align with those of prospective cohort studies and emphasize a need for interventions that target maternal weight during very early gestation, to optimize maternal and offspring health.

    • Wei Perng
    •  & Emily Oken
  • News & Views |

    Faecal microbiota transplantation (FMT) has been suggested to be a therapeutic strategy for inflammatory diseases and it is known that regular physical activity can alter the composition of the gut microbiota. Now, a study proposes that FMT might increase exercise performance in athletes, raising the possibility of ‘faecal doping’.

    • Sarah M. Turpin-Nolan
    • , Michael J. Joyner
    •  & Mark A. Febbraio
  • News & Views |

    Psychological problems such as depression and anxiety can hamper self-management in patients with type 2 diabetes mellitus (T2DM). A new prospective study reported that adults with T2DM and diagnosed anxiety disorder had a higher number of emergency visits and a higher cost status, but not total hospitalization costs, than those without diagnosed anxiety disorder.

    • Frans Pouwer
    •  & Giesje Nefs
  • News & Views |

    Bariatric surgery often produces remission of hyperglycaemia in patients with coexistent obesity and type 2 diabetes mellitus, but the hyperglycaemia is prone to return years later. A prospective study demonstrates that therapy with a glucagon-like peptide 1 receptor agonist can reinstate normal glycaemic control in many of these patients.

    • Clifford J. Bailey
  • News & Views |

    A comprehensive systematic review has recommended decreasing the number of individuals who receive treatment for subclinical hypothyroidism; however, data included in the study are extremely limited for young individuals. Extrapolating data from older individuals is perhaps unwise; therefore, the onus should be on the urgent need for further research.

    • Peter Taylor
    •  & Antonio C. Bianco
  • News & Views |

    Exercise is the elixir of health. However, timing can boost or blunt exercise performance and health benefits. Two complementary studies used transcriptomic and metabolomic tools to dissect how time of day affects the impact of exercise. The findings open new avenues for optimizing timing of physical activity to boost its benefits further.

    • Amandine Chaix
    •  & Satchidananda Panda
  • News & Views |

    Lifestyle interventions in patients with prediabetes can delay the onset of type 2 diabetes mellitus, but long-term data on diabetes complications are lacking. A new report from the Da Qing Study provides data on the effect of lifestyle interventions on diabetes mellitus complications and mortality in patients with prediabetes who were followed up for 30 years.

    • Samuel Dagogo-Jack
  • News & Views |

    High post-challenge glucose plasma concentrations that are observed during pregnancy screening can help to identify women who are at an increased likelihood of later health issues, predominantly cardiovascular diseases. This finding offers a unique opportunity to improve the health of women, but further work is required to translate into clinical benefits.

    • Rosa Corcoy
  • News & Views |

    A positive association between topical corticosteroid use and risk of type 2 diabetes mellitus has been reported in a large European population-based study. However, the increase in risk is small and should not influence the prescribing of topical corticosteroids when clinically indicated.

    • E. C. Johns
    •  & R. M. Reynolds
  • News & Views |

    Thyroid ultrasonography is an important element of clinical thyroid diagnostics. Unfortunately, the results of this technique can vary based on the skill and experience of the operator. A new study suggests that assessment of ultrasound images using artificial intelligence has similar sensitivity and improved specificity compared with the judgement of experienced radiologists.

    • Frederik Verburg
    •  & Christoph Reiners
  • News & Views |

    Alterations in lipid metabolism are closely linked to disorders such as cardiovascular disease, type 2 diabetes mellitus and non-alcoholic fatty liver disease. A multi-omics study on a mouse genetic reference panel uncovers regulatory networks and potential biomarkers of hepatic lipid metabolism.

    • Joel T. Haas
    •  & Bart Staels
  • News & Views |

    By combining genetic, metagenomic and metabolic data in humans, a recent study has identified causal relationships between the capacity of gut microorganisms to produce short-chain fatty acids, such as butyrate and propionate, and metabolic traits of the host, including insulin response during an oral glucose tolerance test and susceptibility to type 2 diabetes mellitus.

    • Matteo Serino
  • News & Views |

    The quality of carbohydrate-rich foods rather than quantity has the strongest effect on major health outcomes. Systematic reviews and meta-analyses of prospective studies report lower mortality and reduced incidence of cardiovascular diseases, type 2 diabetes mellitus and colorectal cancer in people who habitually consume diets rich in fibre and whole grain.

    • Gabriele Riccardi
    •  & Giuseppina Costabile
  • News & Views |

    Jae-Wook Jeong and colleagues report that histone deacetylase 3 (HDAC3) is downregulated in the endometrium of women with endometriosis. In addition, they show that the loss of HDAC3 is associated with aberrant hormonal signalling and increased fibrosis in the endometrium and impaired endometrial receptivity.

    • Sun-Wei Guo
  • News & Views |

    The causes of type 1 diabetes mellitus (T1DM) are unclear; however, a general consensus exists that T1DM is a T cell-mediated autoimmune disease characterized by the selective destruction of insulin-secreting β-cells. Now, two imaging mass cytometry studies of human pancreatic tissue illuminate new biology in the pathogenesis of T1DM.

    • Paolo Pozzilli
    •  & Alberto Signore
  • News & Views |

    Long-term exercise is an important lifestyle factor that can substantially improve the health of older individuals. A new meta-analysis and systematic review builds on previous studies and provides further evidence that exercise interventions can prevent fall-related injuries and fractures in people aged >60 years.

    • Stephen Lord
  • News & Views |

    A recent study shows that a history of rotating night-shift work and an unhealthy lifestyle are associated with increased risk of type 2 diabetes mellitus (T2DM), both independently and synergistically. This is the first large-scale, prospective study to quantify how a healthy lifestyle might partially offset T2DM risk in shift workers.

    • Céline Vetter
    •  & Frank A. J. L. Scheer
  • News & Views |

    As the global increase in type 2 diabetes mellitus has a steep upward slope, meeting the worldwide demand for insulin is an international challenge. Sanjay Basu and colleagues used microsimulation to create scenarios that can inform the design of health-care strategies and insulin requirements for governments and the national and international organizations responsible for formulating treatment guidelines.

    • Margrethe F. Horlyck-Romanovsky
    •  & Anne E. Sumner
  • News & Views |

    A recent study has shown that obesity and ageing induce T cell dysfunction and an upregulation of programmed cell death 1 (PD-1) on T cells across species, which is partially mediated by leptin. However, the polarization of T cells towards an exhaustive phenotype correlated with improved response rates to anti-PD-1 therapy in the setting of obesity.

    • Joanne Lysaght
  • News & Views |

    The recently released physical activity guidelines for Americans advise that adults should do at least 150–300 minutes of moderate intensity aerobic physical activity per week. The scientific evidence clearly shows benefits of physical activity for a wide variety of health outcomes. However, are these guidelines also sufficient to prevent unhealthy weight gain?

    • Ulf Ekelund
    •  & I-Min Lee
  • News & Views |

    Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy are currently the most popular bariatric procedures worldwide; however, there is ongoing debate regarding which is more effective. A new study involving a large multicentre cohort demonstrates significantly more weight loss with RYGB than with sleeve gastrectomy, but with almost double the rate of complications.

    • Jerry T. Dang
    •  & Shahzeer Karmali
  • News & Views |

    In a longitudinal study that tracked BMI from early life, most children with obesity at age 3 years had overweight or obesity by adolescence. Of adolescents with obesity, ~50% were affected by overweight or obesity from age 5 years onwards, and the most rapid increase in BMI had occurred between 2 and 6 years of age.

    • Louise A. Baur
    •  & Sarah P. Garnett
  • News & Views |

    Evidence for the predictive value of IADPSG/WHO2013 diagnostic gestational diabetes mellitus criteria for long-term maternal and offspring outcomes is missing. Recently, William L Lowe Jr and colleagues report a high risk of maternal glycaemic disorders and childhood adiposity 10 to 14 years after untreated gestational diabetes mellitus in the HAPO Follow-up Study.

    • Alexandra Kautzky-Willer
    •  & Jürgen Harreiter
  • News & Views |

    Replacements for the chemical bisphenol A (BPA) have become commonplace in plastics labelled BPA free. However, many of these chemicals have similar structures and properties to BPA. A new study reports that replacement bisphenols, which were discovered as laboratory contaminants, are reproductive toxicants and that their effects might persist for multiple generations.

    • Genoa R. Warner
    •  & Jodi A. Flaws
  • News & Views |

    Pharmacotherapy for obesity, as an adjunct to targeted behavioural modifications, can facilitate weight loss. Previous serotonergic candidates have been withdrawn owing to undesirable cardiovascular effects. A new study in a large sample of high-risk patients shows lorcaserin treatment leads to no greater increase in cardiovascular problems than placebo — what does this result mean for personalized pharmacotherapy for obesity?

    • Carl A. Roberts
    •  & Jason C. G. Halford
  • News & Views |

    Transplanting pancreatic islets in immune-isolating capsules might cure type 1 diabetes mellitus while avoiding the immunosuppression that is normally needed to protect transplanted islets from rejection. A recent study demonstrates that allogeneic islets can survive in capsules with improved biocompatibility without immunosuppression in non-human primates, bringing us one step closer to applying this therapy in humans.

    • Tejal A. Desai
    •  & Qizhi Tang
  • News & Views |

    Intravenous steroid therapy in thyroid eye disease has limitations and is potentially harmful at high doses. A steroid-sparing approach is a reasonable option, but combination therapy must be tested in randomized clinical trials designed to establish the efficacy and the potentially increased risk of adverse effects of combined immunosuppressive treatment.

    • Mario Salvi
  • News & Views |

    The neurotransmitter GABA has been shown to induce the transdifferentiation of α-cells into β-cells, restoring normoglycaemia in a mouse model of diabetes mellitus. A recent paper by Amanda Ackermann and colleagues, however, failed to reproduce these findings. Here, we discuss the discrepant findings and propose a systematic approach to solve the controversy.

    • Decio L. Eizirik
    •  & Esteban N. Gurzov
  • News & Views |

    Detailed profiles of fluctuations in glucose obtained via continuous glucose monitoring highlight the complexity of glucose regulation and underscore that the definition of type 2 diabetes mellitus as a homogeneous disease is an oversimplistic approximation for a heterogeneous metabolic disorder. Whether better phenotyping would ultimately result in improved interventions and outcomes, however, remains largely unproven.

    • Francesco Zaccardi
    •  & Kamlesh Khunti