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Exercise is recommended in the treatment of type 2 diabetes and can improve insulin sensitivity. However, previous evidence suggests that exercise at different times of the day in people with type 2 diabetes may have opposing outcomes on glycaemia. Metformin is the most commonly prescribed initial pharmacological intervention in type 2 diabetes, and may alter adaptions to exercise. It is unknown if there is an interaction between metformin and diurnal exercise outcomes. We aimed to investigate glycaemic outcomes of moderate intensity morning vs. evening exercise in people with type 2 diabetes being prescribed metformin monotherapy. In this study, nine males and nine females with type 2 diabetes undergoing metformin monotherapy (age 61 ± 8.2 years, mean ± SD) completed a 16‐week crossover trial including 2‐week baseline recording, 6 weeks randomly assigned to a morning exercise (07.00–10.00 h) or evening exercise (16.00–19.00 h) and a 2‐week wash‐out period. Exercise arms consisted of 30 min of walking at 70% of estimated max heart rate every other day. Glucose levels were measured with continuous glucose monitors and activity measured by wrist‐worn monitors. Food‐intake was recorded by 4‐day food diaries during baseline, first and last 2 weeks of each exercise arm. There was no difference in exercise intensity, total caloric intake or total physical activity between morning and evening arms. As primary outcomes, acute (24 h) glucose area under the curve (AUC), was lower (P = 0.02) after acute morning exercise (180.6 ± 68.4 mmol/l) compared to baseline (210.3 ± 76.7 mmol/l); and there were no differences identified for glucose (mmol/l) between baseline, morning and evening exercise at any specific time point when data were analysed with two‐way ANOVA. As secondary outcomes, acute glucose AUC was significantly lower (P = 0.01) in participants taking metformin before breakfast (152.5 ± 29.95 mmol/l) compared with participants taking metformin after breakfast (227.2 ± 61.51 mmol/l) only during the morning exercise arm; and during weeks 5–6 of the exercise protocol, glucose AUC was significantly lower (P = 0.04) for participants taking metformin before breakfast (168.8 ± 15.8 mmol/l), rather than after breakfast (224.5 ± 52.0 mmol/l), only during morning exercise. Our data reveal morning moderate exercise acutely lowers glucose levels in people with type 2 diabetes being prescribed metformin. This difference appears to be driven by individuals that consumed metformin prior to breakfast rather than after breakfast. This beneficial effect upon glucose levels of combined morning exercise and pre‐breakfast metformin persisted through the final 2 weeks of the trial. Our findings suggest that morning moderate intensity exercise combined with pre‐breakfast metformin intake may benefit the management of glycaemia in people with type 2 diabetes. Key points: Morning moderate exercise acutely lowers glucose levels in people with type 2 diabetes being prescribed metformin.This difference appears to be driven by individuals that consumed metformin prior to breakfast rather than after breakfast.Morning exercise combined with pre‐breakfast metformin persistently reduced glucose compared to morning exercise combined with post‐breakfast metformin through the final week (week 6) of the intervention.Our study suggests it may be possible to make simple changes to the time that people with type 2 diabetes take metformin and perform exercise to improve their blood glucose. [ABSTRACT FROM AUTHOR]

Several cardiometabolic factors such as diabetes, hypertension and dyslipidemia which are prevalent in older adults with increased body mass index (BMI) may play an important role in sarcopenia development.[[2], [7]] Excess fat mass interrupts the blood glucose pathway and triggers insulin resistance which may then further enhance the development of sarcopenia. Hospitalization rates over 5 years among individuals with BMI >= 30 kg/m SP 2 sp compared to those with normal BMI following adjustments in Model 2 and remained significant with slight attenuation after differences in diabetes status were accounted for [RR (95%CI): 1.90 (1.11-3.28), Model 3]. The direct effect of BMI categories on the risk of all outcomes (Y1, Y2, Y3) was significant for BMI >= 30 kg/m SP 2 sp but not BMI < 18.5 or BMI: 25-29.9 kg/m SP 2 sp compared to those the BMI: 18.5-25 kg/m SP 2 sp group, suggesting the potential mediating role of FBG (Figure 2A-C). [Extracted from the article]

Introduction: To date, COVID‐19 has claimed 4.9 million lives. Diabetes has been identified as an independent risk factor of serious outcomes in people with COVID‐19 infection. Whether that holds true across world regions uniformly has not been previously assessed. Methods: This study offers the first umbrella systematic review and meta‐analysis to analyse the collective and geographically stratified mortality, ICU admission, ventilation requirement, illness severity and discharge rate amongst patients with diabetes. Five databases (EMBASE, MEDLINE, CAB Abstracts, PsychInfo and Web of Science) and 3 additional sources (SSRN's eLibrary, Research Square and MedRxiv) were searched from inception to 30 August 2021. Prospective and retrospective cohort studies, reporting the association between diabetes and one or more COVID‐19 hospitalization outcomes, were included. This meta‐analysis was registered on PROSPERO, CRD42021278579. Abbreviated MeSH terms used for search were as follows: (Diabetes) AND (2019 Novel Coronavirus Disease), adapted per database requirements. Exclusion criteria exclusion criteria were as follows: (1) none of the primary or secondary outcomes of meta‐analysis reported, (2) no confirmed COVID‐19 infection (laboratory or clinical) and (3) no unexposed population (solely patients with diabetes included). Quality of the included studies were assessed using the Newcastle‐Ottawa Scale (NOS) whilst quality of evidence by the GRADE framework. Studies that were clinically homogeneous were pooled. Summative data and heterogeneity were generated by the Cochrane platform RevMan (V. 5.4). Results: Overall, 158 observational studies were included, with a total of 270,212 of participants, median age 59 [53–65 IQR] of who 56.5% were male. A total of 22 studies originated from EU, 90 from Far East, 16 from Middle East and 30 from America. Data were synthesized with mixed heterogeneity across outcomes. Pooled results highlighted those patients with diabetes were at a higher risk of COVID‐19‐related mortality, OR 1.87 [95%CI 1.61, 2.17]. ICU admissions increased across all studies for patients with diabetes, OR 1.59 [95%CI 1.15, 2.18], a result that was mainly skewed by Far East‐originating studies, OR 1.94 [95%CI 1.51, 2.49]. Ventilation requirements were also increased amongst patients with diabetes worldwide, OR 1.44 [95%CI 1.20, 1.73] as well as their presentation with severe or critical condition, OR 2.88 [95%CI 2.29, 3.63]. HbA1C levels under <70 mmol and metformin use constituted protective factors in view of COVID‐19 mortality, whilst the inverse was true for concurrent insulin use. Conclusions: Whilst diabetes constitutes a poor prognosticator for various COVID‐19 infection outcomes, variability across world regions is significant and may skew overall trends. [ABSTRACT FROM AUTHOR]

Background: Patients with Alzheimer's Disease (AD) frequently suffer comorbidities such as type 2 diabetes mellitus (T2DM) alongside shared common pathologies e.g. increased inflammation, endoplasmic reticulum (ER) stress, and impaired energy homeostasis (Plucinska et al., 2016, https://doi.org/10.1007/s00125-016-3960-1). The complexity of neurodegenerative and metabolic diseases requires a systems‐based approach that examines the interplay between brain pathology and metabolic regulation. Emerging evidence points towards abnormal cellular energy regulation as a common denominator, investigated here in hBACE1 associated pathologies (Findlay et al., 2015, https://doi.org/10.3389/fncel.2015.00382). Method: Glucose tolerance tests were performed in male PLB4 and PLB‐WT controls (3 – 8 months) to determine diabetic status (Plucinska et al., 2014, https://doi.org/10.1523/JNEUROSCI.0433-14.2014). Protein analysis was employed to characterise beta‐amyloid/APP processing, ER stress, glucose regulatory signalling, and bioenergetic metabolites in brain, liver, muscle or plasma, and gene expression analysis examined hypothalamic alterations in energy regulation. Result: Neuronal hBACE1 expression caused early pathological cleavage of APP, in parallel with increased brain ER stress (p‐eIF2α) and the chaperone binding immunoglobulin protein (BIP). APP processing declined over time, alongside increased ER stress (IRE1α) in brain and liver. Systemic glucose intolerance was evident from 3 months, varied between tissues and ages, and was confined to the periphery. All key markers normalised to control levels at 8 months. Evidence for altered bioenergetics metabolites (LDH‐A and BCKDH) in brain and liver, also affected by ageing, were detected in PLB4 mice. Furthermore, hypothalamus‐specific changes in energy and appetite regulators (NPY and GLP‐1 receptor) were uncovered in the hBACE1 mice. Conclusion: hBACE1 resulted in early APP misprocessing alongside ER stress but not post‐insulin receptor signalling changes. Peripheral metabolic and bioenergetic alterations were age‐ and tissue‐specific but did not correlate with APP processing. Further tissue analyses are ongoing to determine cellular consequences of hBACE1 expression on systemic bioenergetics. [ABSTRACT FROM AUTHOR]

We examined the relationship between executive functions and both factual and conceptual learning of science, specifically chemistry, in early adolescence. Sixty‐three pupils in their second year of secondary school (aged 12–13 years) participated. Pupils completed tasks of working memory (Spatial Working Memory), inhibition (Stop‐Signal), attention set‐shifting (ID/ED), and planning (Stockings of Cambridge), from the CANTAB. They also participated in a chemistry teaching session, practical, and assessment on the topic of acids and alkalis designed specifically for this study. Executive function data were related to (1) the chemistry assessment which included aspects of factual and conceptual learning and (2) a recent school science exam. Correlational analyses between executive functions and both the chemistry assessment and science grades revealed that science achievements were significantly correlated with working memory. Linear regression analysis revealed that visuospatial working memory ability was predictive of chemistry performance. Interestingly, this relationship was observed solely in relation to the conceptual learning condition of the assessment highlighting the role of executive functions in understanding and applying knowledge about what is learned within science teaching. [ABSTRACT FROM AUTHOR]

Objective The synthetic retinoid fenretinide (FEN) inhibits adiposity in male mice fed a high-fat diet (HFD) in association with alterations in retinoic acid (RA) signaling. Young female mice are protected from obesity via estrogen signaling. We, therefore, investigated whether FEN also influences adiposity in aged female mice differing in parity and whether such effects are mediated by retinoid and estrogen signaling. Methods Aged nulliparous and parous female mice were maintained on HFD ± FEN, and adiposity was assessed. Quantitative polymerase chain reaction was performed on white adipose tissue (WAT), liver, and 3T3-L1 adipocytes treated with RA or FEN ± estrogen. Results Parous females were more obese than nulliparous mice independent of age. FEN-HFD prevented the HFD-induced increase in adiposity and leptin levels independently of parity. FEN-HFD induced retinoid-responsive genes in WAT and liver. Parous females had reduced expression of hepatic estrogen-responsive genes, but FEN-HFD up-regulated WAT Cyp19a1 and Esr2 in parous mice. Estrogen and RA acted synergistically to increase RA receptor-mediated gene expression in 3T3-L1 adipocytes. FEN increased Cyp19a1 and Esr2, similar to our findings in vivo. Conclusions The prevention of adiposity by FEN in response to HFD in female mice seems to involve increased retinoid signaling in association with induction of local estrogen production and estrogen signaling in WAT. [ABSTRACT FROM AUTHOR]

Methionine restriction ( MR) decreases body weight and adiposity and improves glucose homeostasis in rodents. Similar to caloric restriction, MR extends lifespan, but is accompanied by increased food intake and energy expenditure. Most studies have examined MR in young animals; therefore, the aim of this study was to investigate the ability of MR to reverse age-induced obesity and insulin resistance in adult animals. Male C57BL/6J mice aged 2 and 12 months old were fed MR (0.172% methionine) or control diet (0.86% methionine) for 8 weeks or 48 h. Food intake and whole-body physiology were assessed and serum/tissues analyzed biochemically. Methionine restriction in 12-month-old mice completely reversed age-induced alterations in body weight, adiposity, physical activity, and glucose tolerance to the levels measured in healthy 2-month-old control-fed mice. This was despite a significant increase in food intake in 12-month-old MR-fed mice. Methionine restriction decreased hepatic lipogenic gene expression and caused a remodeling of lipid metabolism in white adipose tissue, alongside increased insulin-induced phosphorylation of the insulin receptor ( IR) and Akt in peripheral tissues. Mice restricted of methionine exhibited increased circulating and hepatic gene expression levels of FGF21, phosphorylation of eIF2a, and expression of ATF4, with a concomitant decrease in IRE1α phosphorylation. Short-term 48-h MR treatment increased hepatic FGF21 expression/secretion and insulin signaling and improved whole-body glucose homeostasis without affecting body weight. Our findings suggest that MR feeding can reverse the negative effects of aging on body mass, adiposity, and insulin resistance through an FGF21 mechanism. These findings implicate MR dietary intervention as a viable therapy for age-induced metabolic syndrome in adult humans. [ABSTRACT FROM AUTHOR]

Research examining cognition and science learning has focused on working memory, but evidence implicates a broader set of executive functions. The current study examined executive functions and learning of biology in young adolescents. Fifty-six participants, aged 12-13 years, completed tasks of working memory (Spatial Working Memory), inhibition (Stop-Signal), attention set-shifting (ID/ED) and planning (Stockings of Cambridge), from the Cambridge Neuropsychological Test Automated Battery. They also participated in a biology teaching session, practical and assessment on the topic of DNA designed specifically for the current study that measured (a) memory for biology facts taught and (b) understanding of information learned in the practical. Linear regression analysis revealed that planning ability predicted performance on the factual assessment, and both spatial working memory and planning were predictive of performance on the conceptual assessment. The findings suggest that planning ability is important in learning biological facts but that a broader set of executive functions are important for conceptual learning, highlighting the role of executive functions in understanding and applying knowledge about what is learned within science teaching. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]