Clinical utility of self-reported sleep duration and insomnia symptoms in type 2 diabetes prediction.

Aims/hypothesis: Suboptimal sleep health is linked to higher risks for incident type 2 diabetes. We aimed to assess the clinical utility of adding self-reported sleep traits to a type 2 diabetes prediction model.

Methods: In this cohort study, we used UK Biobank data and Cox proportional hazards models to examine how self-reported sleep duration and insomnia symptoms were associated with incident type 2 diabetes risk.

Randomised trial comparing weight loss through lifestyle and GLP-1 receptor agonist therapy in people with MASLD.

Background & Aims: Glucagon-like peptide 1 receptor agonist (GLP-1RA) therapies deliver histological benefit in people with metabolic dysfunction-associated steatotic liver disease (MASLD). Multiple mechanisms may be important including weight loss, improved glycaemic control and putative direct tissue-specific actions. Following cessation of GLP1-RA therapy, weight regain is common.

Temporal mineralocorticoid receptor activation regulates the molecular clock and transcription of cardiovascular disease modulators in myeloid cells.

Inappropriate mineralocorticoid receptor (MR) activation in monocytes/macrophages promotes cardiac inflammation and fibrosis. However, the specific pathways whereby the MR regulates macrophage phenotype are not fully defined. We recently identified bidirectional regulation of the MR and the molecular circadian clock in cardiac cells.

Is It Possible to Screen for Primary Aldosteronism Effectively in Primary Care?

Objective: Primary aldosteronism (PA) is the commonest secondary cause of hypertension but case-detection remains a challenge. Screening is usually performed in secondary care using an aldosterone:renin ratio (ARR) measurement. Here, we describe the outcomes of screening in primary care, in Oxfordshire, UK.

LRP5 promotes adipose progenitor cell fitness and adipocyte insulin sensitivity.

Background: WNT signaling plays a key role in postnatal bone formation. Individuals with gain-of-function mutations in the WNT co-receptor LRP5 exhibit increased lower-body fat mass and potentially enhanced glucose metabolism, alongside high bone mass. However, the mechanisms by which LRP5 regulates fat distribution and its effects on systemic metabolism remain unclear.

Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis.

Rheumatoid arthritis is a chronic inflammatory disease that shows characteristic diurnal variation in symptom severity, where joint resident fibroblast-like synoviocytes (FLS) act as important mediators of arthritis pathology. We investigate the role of FLS circadian clock function in directing rhythmic joint inflammation in a murine model of inflammatory arthritis. We demonstrate FLS time-of-day-dependent gene expression is attenuated in arthritic joints, except for a subset of disease-modifying genes.

The role of accelerometer-derived sleep traits on glycated haemoglobin and glucose levels: a Mendelian randomization study.

Self-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar observations in small studies using accelerometer-derived sleep traits. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not others, on glycated haemoglobin (HbA1c). To explore potential effects, we used MR methods to assess effects of accelerometer-derived sleep traits (duration, mid-point least active 5-h, mid-point most active 10-h, sleep fragmentation, and efficiency) on HbA1c/glucose in European adults from the UK Biobank (UKB) (n = 73,797) and the MAGIC consortium (n = 146,806).

Self-supervised learning of accelerometer data provides new insights for sleep and its association with mortality.

Sleep is essential to life. Accurate measurement and classification of sleep/wake and sleep stages is important in clinical studies for sleep disorder diagnoses and in the interpretation of data from consumer devices for monitoring physical and mental well-being. Existing non-polysomnography sleep classification techniques mainly rely on heuristic methods developed in relatively small cohorts.

Shift work and evening chronotype are associated with hepatic fat fraction and non-alcoholic fatty liver disease in 282,303 UK biobank participants.

Background And Aims: Non-alcoholic fatty liver disease (NAFLD) has rapidly become the most common liver disease worldwide. Modern lifestyles have been linked to this rise in prevalence with changes in rhythmic human behaviour emerging as a possible mechanism. We investigated how shift working patterns and chronotype were associated with hepatic fat fraction and NAFLD in 282,303 UK Biobank participants.

Circadian regulation of liver metabolism: experimental approaches in human, rodent, and cellular models.

Circadian rhythms are endogenous oscillations with approximately a 24-h period that allow organisms to anticipate the change between day and night. Disruptions that desynchronize or misalign circadian rhythms are associated with an increased risk of cardiometabolic disease. This review focuses on the liver circadian clock as relevant to the risk of developing metabolic diseases including nonalcoholic fatty liver disease (NAFLD), insulin resistance, and type 2 diabetes (T2D).

Associations between sleep health and grey matter volume in the UK Biobank cohort ( = 33 356).

As suggested by previous research, sleep health is assumed to be a key determinant of future morbidity and mortality. In line with this, recent studies have found that poor sleep is associated with impaired cognitive function. However, to date, little is known about brain structural abnormalities underlying this association.

Self-supervised learning of accelerometer data provides new insights for sleep and its association with mortality.

Background: Sleep is essential to life. Accurate measurement and classification of sleep/wake and sleep stages is important in clinical studies for sleep disorder diagnoses and in the interpretation of data from consumer devices for monitoring physical and mental well-being. Existing non-polysomnography sleep classification techniques mainly rely on heuristic methods developed in relatively small cohorts.

Timing of energy intake and the therapeutic potential of intermittent fasting and time-restricted eating in NAFLD.

Non-alcoholic fatty liver disease (NAFLD) represents a major public health concern and is associated with a substantial global burden of liver-related and cardiovascular-related morbidity and mortality. High total energy intake coupled with unhealthy consumption of ultra-processed foods and saturated fats have long been regarded as major dietary drivers of NAFLD. However, there is an accumulating body of evidence demonstrating that the timing of energy intake across a the day is also an important determinant of individual risk for NAFLD and associated metabolic conditions.

Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad?

It is estimated that 2% to 3% of the population are currently prescribed systemic or topical glucocorticoid treatment. The potent anti-inflammatory action of glucocorticoids to deliver therapeutic benefit is not in doubt. However, the side effects associated with their use, including central weight gain, hypertension, insulin resistance, type 2 diabetes (T2D), and osteoporosis, often collectively termed iatrogenic Cushing's syndrome, are associated with a significant health and economic burden.

Consequences of collagen induced inflammatory arthritis on circadian regulation of the gut microbiome.

The gut microbiota is important for host health and immune system function. Moreover autoimmune diseases, such as rheumatoid arthritis, are associated with significant gut microbiota dysbiosis, although the causes and consequences of this are not fully understood. It has become clear that the composition and metabolic outputs of the microbiome exhibit robust 24 h oscillations, a result of daily variation in timing of food intake as well as rhythmic circadian clock function in the gut.

Determining the temporal, dose, and composition effects of nutritional substrates in an in vitro model of intrahepatocellular triglyceride accumulation.

Pathological accumulation of intrahepatic triglyceride underpins the early stages of nonalcoholic fatty liver disease (NAFLD) and can progress to fibrosis, cirrhosis, and cancer of the liver. Studies in humans suggest that consumption of a diet enriched in saturated compared to unsaturated fatty acids (FAs), is more detrimental to liver fat accumulation and metabolism. However, the reasons for the divergence remain unclear and physiologically-relevant cellular models are required.

Chronovaccination: Harnessing circadian rhythms to optimize immunisation strategies.

Vaccination, as a public health measure, offers effective protection of populations against infectious diseases. Optimising vaccination efficacy, particularly for higher-risk individuals, like the elderly whose immunocompromised state can prevent the development of robust vaccine responses, is vital. It is now clear that 24-hour circadian rhythms, which govern virtually all aspects of physiology, can generate oscillations in immunological responses.

Circadian Rhythm and Nuclear Receptors.

All life of Earth has evolved mechanisms to track time. This permits anticipation of predictable changes in light/dark, and in most cases also directs fed/fasted cycles, and sleep/wake. The nuclear receptors enjoy a close relationship with the molecular machinery of the clock.

HaloChIP-seq for Antibody-Independent Mapping of Mouse Transcription Factor Cistromes .

Chromatin immunoprecipitation (ChIP) maps, on a genome-wide scale, transcription factor binding sites, and the distribution of other chromatin-associated proteins and their modifications. As such, it provides valuable insights into mechanisms of gene regulation. However, successful ChIP experiments are dependent on the availability of a high-quality antibody against the target of interest.

Circadian rhythms in psoriasis and the potential of chronotherapy in psoriasis management.

The physiology and pathology of the skin are influenced by daily oscillations driven by a master clock located in the brain, and peripheral clocks in individual cells. The pathogenesis of psoriasis is circadian-rhythmic, with flares of disease and symptoms such as itch typically being worse in the evening/night-time. Patients with psoriasis have changes in circadian oscillations of blood pressure and heart rate, supporting wider circadian disruption.