Physical exercise (PE) may be important for glucose metabolism. Therefore, this systematic review and meta-analysis aims to investigate the effect of PE performed in the morning versus afternoon or evening on glycemia parameters in human intervention studies. MEDLINE and Embase.com were searched until February 2023 for intervention studies in the general adult population, examining the effect the timing of PE on glycemia parameters after one or multiple bouts of exercise. Results were meta-analysed using a random-effects models where appropriate or were described using qualitative synthesis. 55,569 publications were screened for a series of reviews, of which 20 studies (680 participants) were included in this review. In studies including one bout of PE (n = 12), glucose levels measured directly after PE were 0.26 mmol/L (95

To assess the clinical value of [18F]fluoroethyl-L-tyrosine PET ([18F]FET-PET) correlated with MRI in patients with functioning pituitary adenoma (FPA) with negative or equivocal conventional MRIs during diagnosis, persistent disease and recurrence. Retrospective observational cohort study of 34 patients with FPAs who underwent a total of 37 [18F]FET-PETs (Cushing’s disease: n = 19, acromegaly: n = 14, prolactinoma: n = 3, and TSH producing adenoma: n = 1) between January 2022 and April 2025. The clinical performance was assessed in the surgically treated cohort, using confirmative histopathology and/or postoperative remission as reference standard. [18F]FET-PET identified a single lesion in 28 scans (76

Abstract Purpose Prader-Willi Syndrome (PWS) is a rare genetic disorder with a heterogeneous phenotype, caused by loss of expression of genes on the paternally inherited chromosome 15q11.2-15q13.3, primarily due to paternal deletion of these genes. PWS with paternal deletion can be categorised into sub-genotype 1 (PWS T1) and sub-genotype 2 (PWS T2), with PWS T1 encompassing a more extensive genetic deletion with distinct clinical manifestations. Neuroimaging studies have shown structural alterations in the hypothalamus and other brain structures of PWS patients, but no distinctions were made between PWS sub-genotypes in patients with a paternal deletion. This study aimed to differentiate between PWS T1 and T2, exploring volumetric differences of the hypothalamus and other brain structures using T1-weighted MRI. Methods Structural T1-weighted MRI images from 6 PWS T1 patients, 6 PWS T2 patients, and 13 controls underwent pre-processing and segmentation. Brain structure volumes were normalised for intracranial volume using the residual method. Right-sided hypothalamic data were excluded due to unreliable segmentation outcomes. Results Total intracranial volume was significantly smaller in PWS patients compared to controls. After adjustment, the left-sided hypothalamus and hypothalamic subunit volumes were smaller in the PWS group. Lateral ventricle, third ventricle, cerebrospinal fluid and total ventricle & choroid plexus volume were significantly larger in the PWS group compared to the control group, whereas mid-posterior corpus callosum volume was smaller. Cerebellar volume was smaller in PWS T2 patients compared to PWS T1 patients. Conclusion Future research should further distinguish PWS sub-genotypes to enhance personalised medicine for PWS patients.

AIMS:This systematic review and meta-analysis aims to summarize the effect of the timing of meal intake on glycaemic outcomes in human intervention studies. DATA SYNTHESIS:Medline and Embase.com were searched for intervention studies in the adult population directly comparing the timing of meal intake on glycaemic outcomes. Results were meta-analysed in random-effects models or qualitatively described using vote counting. Of 55,569 publications screened, 44 studies were included. Study duration was up to one week (n = 37) or 2-12 weeks (n = 7). Shorter studies demonstrated that early meal timing, compared to late meal timing, significantly lowers postprandial 2-h glucose (-1.51 [-2.03, -0.99] mmol/L, I2 = 79%) and postprandial peak glucose (-1.03 [-1.63, -0.44] mmol/L, I2 = 61%). Mean glucose over 24-h, largest glucose peak over 24-h, fasting glucose, fasting insulin and postprandial 2-h insulin also showed the same direction, albeit not significant. In longer studies, fasting glucose seemed lower in early meal timing (-0.05 [-0.13, 0.02] mmol/L, I2 = 27%). Conversely, fasting insulin and HOMA-IR showed no differences. CONCLUSIONS:This systematic review and meta-analysis shows physiological plausibility that early meal intake may be beneficial for glycaemic control, compared to late meal intake. However, this is only seen in studies with a duration of up to one week. Moreover, the high heterogeneity between study designs, interventions, and methods precludes definite conclusions and clinical recommendations. Larger and longer trials, that control for total energy intake, weight loss, and rhythms of other Zeitgebers, are needed before chrono-nutrition principles can be translated into clinical dietary guidelines for glycaemic control.

Abstract Context Immunohistochemistry (IHC) of cell lineage-specific transcription factors (TFs) has been added to the histopathological classification of pituitary adenomas since 2017, resulting in new histopathological subtypes of TF+/hormone- non-functioning pituitary adenomas (NFPAs) and a reduction in the prevalence of null cell adenomas (NCAs). Objective To evaluate associations between expression of cell lineage-specific TFs by IHC and radiological invasion and prognosis of NFPAs. Data sources A literature search in Medline, Embase, and CENTRAL was performed from inception up to July 11th 2023. Study selection Eligible studies were cohort studies reporting on radiological invasion, recurrence and/or radiotherapy in patients with NFPAs who tested positive for one cell lineage-specific TF or negative for all three. Finally, 27 out of 1985 studies were included. Data extraction Two authors independently extracted data and critically appraised risk of bias using the QUIPS tool. Data synthesis Random-effects inverse variance models were used to pool effect sizes. Prevalence rate ratios (PRR) were calculated using the Mantel-Haenszel method. Cavernous sinus invasion was more prevalent in NCAs and TPIT+ NFPAs compared with SF1+ NFPAs (PRR 1.60, 95% confidence interval (CI) 1.22-2.08, I2 10%, 95% prediction interval (PrI) 1.23-2.06, p=0.0036, and PRR 1.43, 95% CI 1.21-1.70, I2 0%, 95% PrI 1.17-1.76, p=0.0017, respectively), and in NCAs compared with PIT1+ (PRR 1.44, 95% CI 1.01-2.06, I2 0%, 95% PrI 0.83-2.50, p=0.0454). Limited number of studies precluded data syntheses of recurrence and radiotherapy. Conclusions The use of cell lineage-specific TFs by IHC enables to detect histopathological subtypes of NFPAs with distinct clinical behaviour.

INTRODUCTION:The circadian timing system regulates diurnal sleep-wake rhythm. Previously, we showed that, in patients undergoing elective surgery, sleep-wake timing is altered and post-operative sleep quality is reduced. However, how the timing of the surgical procedure affects the disturbance and what other factors affect this disturbance remain unknown. METHODS:Single-centre prospective observational study investigating the influence of surgery timing on post-operative sleep in adult patients (≥18 years) undergoing elective surgery. Sleep-wake timing was measured from three nights before until seven nights after surgery with a daily sleeping log. Primary outcome was post-operative midpoint of sleep shift between patients undergoing morning and afternoon surgeries. Secondary outcomes included factors affecting sleep timing disturbance and changes in subjective sleep quality. RESULTS:We included 259 patients: 144 patients underwent morning procedures (08:00 h-12:00 h) and 115 underwent afternoon procedures (12:00 h-17:00 h). Both groups had significant phase advance of midpoint of sleep on the night after surgery when compared with three nights before surgery (mean - 00:41 h, 95% CI -00:27 h to -00:54 h, p < .001, for morning surgery and mean - 00:28 h, 95% CI -00:09 h to -00:46 h, p = .003, for afternoon surgery). However, there was no between-group difference (mean - 00:13 h, 95% CI -00:35 h-00:09 h, p = .25). Reduction of sleep quality was also similar. Phase advance was larger for patients with an evening chronotype or with lower pre-operative sleep quality. Decline of sleep quality after surgery was larger for patients with an evening chronotype, longer procedures or better pre-operative sleep quality. CONCLUSION:Our results suggest that the timing of surgery between 08:00 h and 17:00 h does not modulate the effect of anaesthesia and surgery on phase of the sleep-wake rhythm in patients undergoing elective surgery with a low pre-operative risk of delirium. EDITORIAL COMMENT:Timing of surgery may impact post-operative sleep. However, in this prospective cohort study of elective surgical patients, sleep-wake timing and post-operative sleep quality did not differ between those undergoing morning versus afternoon surgery.

Women with type 1 diabetes experience changes in insulin requirements in pregnancy and throughout the menstrual cycle. It remains to be explored whether women with type 1 diabetes perceive changes in glucose regulation during and after the menopausal transition, another period of marked hormonal change in a woman’s life. We conducted a cross-sectional survey to investigate whether women with type 1 diabetes perceive changes in glucose regulation after their final menstrual period. The online questionnaires were distributed through advertisements in hospitals and through online platforms for people living with type 1 diabetes in the Netherlands. Postmenopausal women (≥1 year of amenorrhoea) with type 1 diabetes, aged 45–65 years, were included. Participants with primary amenorrhoea, premenopausal hysterectomy or a postmenopausal diabetes diagnosis were excluded from the study. The primary outcome was the extent to which participants perceived changes in their glucose regulation following their final menstrual period, assessed using a five-point Likert scale. Menopausal symptom severity was estimated using the Greene climacteric scale (GCS). Questionnaires from a total of 159 women were eligible for inclusion. Participants had a mean age of 54.9 years (SD 3.8), a mean diabetes duration of 30.3 years (SD 12.8), and had their final menstrual period at a mean age of 50.1 years (SD 5.0). Overall, 67.4 https://doi.org/10.34894/84QJOO .

Time-restricted eating has shown great promise for improving metabolic health in humans with obesity, but its mechanism is still not completely resolved. In this study, we investigated how time-restricted feeding (TRF) affects microglial immunometabolism using Wistar rats. High-fat diet (HFD)-fed animals became obese, but restricting food intake to the active phase reduced fat mass, reinforced the rhythmicity of the microglial transcriptome, and prevented an increase in hypothalamic microglial cell numbers. However, TRF failed to reverse HFD-induced microglial immune dysfunction and metabolic disturbances, including suppressed electron transport chain activity, increased lipid metabolism gene expression, and impaired metabolic flexibility. These findings suggest that obesity-driven microglial immunometabolic reprogramming persists despite TRF-induced weight loss and may contribute to obesogenic memory and weight regain after weight loss induced by dietary interventions.

The hypothalamic suprachiasmatic nucleus (SCN), the circadian pacemaker of the mammalian brain, integrates both environmental and endogenous information to modulate various physiological and behavioral processes. Both light and physical activity entrain SCN circadian rhythmicity, but the underlying molecular mechanisms for physical activity remain elusive. Repetitive neuronal stimulation results in accumulation of the stable transcription factor ΔFOSB, that has been implicated in long-term brain plasticity, altered neuronal excitability, and changes in behavior. In rodents, voluntary wheel running (VWR) mimics aspects of exercise training and increases ΔFOSB in several brain regions. Whether VWR also alters ΔFOSB in the SCN is unexplored. Here, young-adult male and female Wistar rats were housed sedentary or allowed to run for four weeks followed by quantification of ΔFOSB in the SCN. VWR lowered SCN ΔFOSB-positive cell numbers in males and females compared to sedentary housing. Total running distance did not correlate with ΔFOSB suppression. Analysis taking estrous cycle into account revealed that ΔFOSB-positive cell numbers were cyclic in sedentary females, being lowest during proestrus and highest during diestrus. Remarkably, this cyclicity was absent in runners, where ΔFOSB-positive cell numbers remained comparable to those observed during proestrus in sedentary controls. Finally, estradiol replacement following ovariectomy in sedentary females lowered SCN ΔFOSB-positive cell numbers. Thus, VWR and estrous cycle, via, at least in part, estradiol, modulate SCN ΔFOSB. Given its role in long-term plasticity and behavioral adaptations, ΔFOSB may provide a molecular link between VWR and/or estrous cycle and the output of the SCN and its related behavioral adaptations.

CONTEXT:Immunohistochemistry (IHC) of cell lineage-specific transcription factors (TFs) has been added to the histopathological classification of pituitary adenomas since 2017, resulting in new histopathological subtypes of TF+/hormone-non-functioning pituitary adenomas (NFPAs) and a reduction in the prevalence of null cell adenomas (NCAs). OBJECTIVE:This work aimed to evaluate associations between expression of cell lineage-specific TFs by IHC and radiological invasion and prognosis of NFPAs. DATA SOURCES:A literature search in Medline, Embase, and CENTRAL was performed from inception up to July 11, 2023. STUDY SELECTION:Eligible studies were cohort studies reporting on radiological invasion, recurrence, and/or radiotherapy in patients with NFPAs who tested positive for one cell lineage-specific TF or negative for all 3. Finally, 27 out of 1985 studies were included. DATA EXTRACTION:Two authors independently extracted data and critically appraised risk of bias using the Quality In Prognostic Studies (QUIPS) tool. DATA SYNTHESIS:Random-effects inverse variance models were used to pool effect sizes. Prevalence rate ratios (PRRs) were calculated using the Mantel-Haenszel method. Cavernous sinus invasion was more prevalent in NCAs and TPIT+ NFPAs compared with SF1+ NFPAs (PRR 1.60; 95% CI, 1.22-2.08, I2 10%, 95% prediction interval [PrI] 1.23-2.06; P = .0036, and PRR 1.43; 95% CI, 1.21-1.70, I2 0%, 95% PrI 1.17-1.76; P = .0017, respectively), and in NCAs compared with PIT1+ (PRR 1.44; 95% CI, 1.01-2.06, I2 0%, 95% PrI 0.83-2.50; P = .0454). A limited number of studies precluded data syntheses of recurrence and radiotherapy. CONCLUSION:The use of cell lineage-specific TFs by IHC enables to detect histopathological subtypes of NFPAs with distinct clinical behavior.

Excess caloric intake and insufficient physical activity are the two major drivers underlying the global obesity and type 2 diabetes mellitus epidemics. However, circadian misalignment of caloric intake and physical activity, as commonly experienced by nightshift workers, can also have detrimental effects on body weight and glucose homeostasis. We have previously reported that combined restriction of eating and voluntary wheel running to the inactive phase (i.e., a rat model for circadian misalignment) shifted liver and muscle clock rhythms by ~12 h and prevented the reduction in the amplitude of the muscle clock oscillation otherwise induced by light-phase feeding. Here, we extended on these findings and investigated how a high-fat diet (HFD) affects body composition and liver and muscle clock gene rhythms in male Wistar rats while restricting both eating and exercise to either the inactive or active phase. To do this, we used four experimental conditions: sedentary controls with no wheel access on a non-obesogenic diet (NR), sedentary controls with no wheel access on an HFD (NR-H), and two experimental groups on an HFD with simultaneous access to a running wheel and HFD time-restricted to either the light phase (light-run-light-fed + HFD, LRLF-H) or the dark phase (dark-run-dark-fed + HFD. DRDF-H). Consumption of an HFD did not alter the daily running distance of the time-restricted groups but did increase the running intensity in the LRLF-H group compared to a previously published LRLF chow fed group. However, no such increase was observed for the DRDF-H group. LRLF-H ameliorated light phase-induced disturbances in the soleus clock more effectively than under chow conditions and had a protective effect against HFD-induced changes in liver clock gene expression. Together with (our) previously published results, these data suggest that eating healthy and being active at the wrong time of the day can be as detrimental as eating unhealthy and being active at the right time of the day.

The circadian timing system controls glucose metabolism in a time-of-day dependent manner. In mammals, the circadian timing system consists of the main central clock in the bilateral suprachiasmatic nucleus (SCN) of the anterior hypothalamus and subordinate clocks in peripheral tissues. The oscillations produced by these different clocks with a period of approximately 24-h are generated by the transcriptional-translational feedback loops of a set of core clock genes. Glucose homeostasis is one of the daily rhythms controlled by this circadian timing system. The central pacemaker in the SCN controls glucose homeostasis through its neural projections to hypothalamic hubs that are in control of feeding behavior and energy metabolism. Using hormones such as adrenal glucocorticoids and melatonin and the autonomic nervous system, the SCN modulates critical processes such as glucose production and insulin sensitivity. Peripheral clocks in tissues, such as the liver, muscle, and adipose tissue serve to enhance and sustain these SCN signals. In the optimal situation all these clocks are synchronized and aligned with behavior and the environmental light/dark cycle. A negative impact on glucose metabolism becomes apparent when the internal timing system becomes disturbed, also known as circadian desynchrony or circadian misalignment. Circadian desynchrony may occur at several levels, as the mistiming of light exposure or sleep will especially affect the central clock, whereas mistiming of food intake or physical activity will especially involve the peripheral clocks. In this review, we will summarize the literature investigating the impact of circadian desynchrony on glucose metabolism and how it may result in the development of insulin resistance. In addition, we will discuss potential strategies aimed at reinstating circadian synchrony to improve insulin sensitivity and contribute to the prevention of type 2 diabetes.

Background The circadian timing system coordinates daily cycles in physiological functions, including glucose metabolism and insulin sensitivity. Here, the aim was to characterise the 24-h variation in glucose levels in critically ill patients during continuous enteral nutrition after controlling for potential sources of bias. Methods Time -stamped clinical data from adult patients who stayed in the Intensive Care Unit (ICU) for at least 4 days and received enteral nutrition were extracted from the Medical Information Mart for Intensive Care (MIMIC) -IV database. Linear mixed -effects and XGBoost modelling were used to determine the effect of time of day on blood glucose values. Findings In total, 207,647 glucose measurements collected during enteral nutrition were available from 6,929 ICU patients (3,948 males and 2,981 females). Using linear mixed -effects modelling, time of day had a significant effect on blood glucose levels (p < 0.001), with a peak of 9.6 [9.5 - 9.6; estimated marginal means, 95% CI] mmol/L at 10:00 in the morning and a trough of 8.6 [8.5 - 8.6] mmol/L at 02:00 at night. A similar impact of time of day on glucose levels was found with the XGBoost regression model. Interpretation These results revealed marked 24-h variation in glucose levels in ICU patients even during continuous enteral nutrition. This 24-h pattern persists after adjustment for potential sources of bias, suggesting it may be the result of endogenous biological rhythmicity.

Background Chronotype, an individual’s preferred sleep-wake timing, is influenced by sex and age. Men report a later chronotype than women and age is associated with earlier chronotype. The sex-related changes in chronotype coincide with puberty and menopause. However, the effects of sex hormones on human chronotype remain unclear. Aim To examine the impact of 3 months of gender-affirming hormone therapy (GAHT) on chronotype in transgender persons. Methods This study used data from 93 participants from the prospective RESTED cohort, including 49 transmasculine (TM) participants starting testosterone and 44 transfeminine (TF) participants starting estrogens and antiandrogens. Midpoint of sleep and sleep duration were measured using the ultra-short Munich ChronoType Questionnaire (µMCTQ). Results After 3 months of GAHT, TM participants’ midpoint of sleep increased by 24 minutes (95%CI: 3 to 45), whereas TF participants’ midpoint of sleep decreased by 21 minutes (95%CI: −38 to −4). Total sleep duration did not change significantly in either group. Conclusion This study provides the first prospective assessment of sex hormone use and chronotype in transgender persons, showing that GAHT can change chronotype in line with cisgender sex differences. These findings provide a basis for future studies on biological mechanisms and clinical consequences of chronotype changes.

AIMS:Alterations in sleep timing can lead to disturbances in glycaemic control, although the evidence is inconsistent. Therefore, this systematic review summarizes results from human intervention studies of altered sleep timing on glycaemic outcomes. MATERIALS AND METHODS:As part of a broader search on the effect of altering timing of sleep, physical activity and dietary intake, Medline and Embase were searched from inception to February 2023, and subsequent reference searches were done. With the help of a machine learning-aided program 'ASReview', we selected any type of intervention study in the general adult population, which acutely delayed sleep by ≥2 h for at least one night, while the total time in bed was the same between early and late sleep. Quality assessment was done using the quality assessment tool for quantitative studies. RESULTS:In total, 14 studies (159 adults with normal or increased weight) were identified. Methodological quality was high (n = 4), moderate (n = 7) or low (n = 3). Acute delays of sleep onset showed unfavourable effects in 10 out of 27 measured glycaemic outcomes (one-six studies reported on each outcome) with outcomes mostly measured in the postprandial period, compared to (early) nighttime sleep. CONCLUSIONS:Acutely delaying sleep timing might have unfavourable effects on glycaemic outcomes, compared to (early) nighttime sleep. Future research does however need better controlled trials, also measuring and controlling sleep quantity, sleep quality, physical activity and dietary intake, with longer follow-up periods, consistent outcomes and designs and more diverse populations to provide targeted advice regarding the optimal timing for sleep. PROTOCOL REGISTRATION:This review is part of a larger search 'The effect of altering timing of physical activity, sleep and energy intake on glycaemia and Type 2 Diabetes risk in humans', of which the protocol was registered in the PROSPERO database on 27 November 2021 under number: CRD42021287828.