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INTRODUCTION: Metabolic flexibility (MetF), defined as the ability to switch between fat and glucose oxidation, is increasingly recognised as a critical marker for assessing responses to dietary interventions. Previously, we showed that the consumption of multifibre bread improved insulin sensitivity and reduced low-density lipoprotein cholesterol (LDLc) levels in overweight and obese individuals. As a secondary objective, we aimed to explore whether our intervention could also improve MetF. METHODS: In this study, 39 subjects at cardiometabolic risk participated in a double-blind, randomised, crossover trial lasting 8 weeks, repeated twice. During each phase, participants consumed either 150 g of standard bread daily or bread enriched with a mixture of seven dietary fibres. MetF response was assessed using a mixed-meal tolerance test (MMTT), analysing changes in respiratory quotient (∆RQ) measured using indirect calorimetry. RESULTS: Although there were no significant differences in ∆RQ changes induced by dietary fibre between the two diets, these changes were positively correlated with postprandial triglyceride excursion (∆TG) at baseline. Subgroup analysis of baseline fasting and postprandial plasma metabolites was conducted to characterise MetF responders. These responders exhibited higher baseline fasting LDLc levels and greater post-MMTT ∆TG. CONCLUSION: In conclusion, although dietary fibres did not directly impact MetF in this study, our findings highlight potential determinants of MetF response, warranting further investigation in dedicated future interventions.
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Bedrest shifts fasting and postprandial fuel selection towards carbohydrate use over lipids, potentially affecting astronauts' performance and health. We investigated whether this change occurs in astronauts after at least 3 months onboard the International Space Station (ISS). We further explored the associations with diet, physical activity (PA), and body composition. Before and during spaceflight, respiratory quotient (RQ), carbohydrate, and fat oxidation were measured by indirect calorimetry before and following a standardized meal in 11 males (age = 45.7 [SD 7.7] years, BMI = 24.3 [2.1] kg m-²). Postprandial substrate use was determined by 0-to-260 min postprandial incremental area under the curve (iAUC) of nutrient oxidation and the difference between maximal postprandial and fasting RQ (ΔRQ). Food quotient (FQ) was calculated from diet logs. Fat (FM) and fat-free mass (FFM) were measured by hydrometry and PA by accelerometry and diary logs. Spaceflight increased fasting RQ (P = 0.01) and carbohydrate oxidation (P = 0.04) and decreased fasting lipid oxidation (P < 0.01). An increase in FQ (P < 0.001) indicated dietary modifications onboard the ISS. Spaceflight-induced RQ changes adjusted for ground RQ correlated with inflight FQ (P < 0.01). In postprandial conditions, nutrient oxidation and ΔRQ were unaffected on average. Lipid oxidation changes negatively correlated with FFM changes and inflight aerobic exercise and positively with FM changes. The opposite was observed for carbohydrate oxidation. ΔRQ changes were negatively and positively related to FM and FFM changes, respectively. In conclusion, fasting substrate oxidation shift observed during spaceflight may primarily result from dietary modifications. Between-astronaut variability in postprandial substrate oxidation depends on body composition changes and inflight PA.
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It is unclear how skeletal muscle metabolism and mitochondrial function adapt to long duration bed rest and whether changes can be prevented by nutritional intervention. The present study aimed (1) to assess the effect of prolonged bed rest on skeletal muscle mitochondrial function and dynamics and (2) to determine whether micronutrient supplementation would mitigate the adverse metabolic effect of bed rest. Participants were maintained in energy balance throughout 60 days of bed rest with micronutrient supplementation (INT) (body mass index: 23.747 ± 1.877 kg m-2 ; 34.80 ± 7.451 years; n = 10) or without (control) (body mass index: 24.087 ± 2.088 kg m-2 ; 33.50 ± 8.541 years; n = 10). Indirect calorimetry and dual-energy x-ray absorptiometry were used for measures of energy expenditure, exercise capacity and body composition. Mitochondrial respiration was determined by high-resolution respirometry in permeabilized muscle fibre bundles from vastus lateralis biopsies. Protein and mRNA analysis further examined the metabolic changes relating to regulators of mitochondrial dynamics induced by bed rest. INT was not sufficient in preserving whole body metabolic changes conducive of a decrease in body mass, fat-free mass and exercise capacity within both groups. Mitochondrial respiration, OPA1 and Drp1 protein expression decreased with bed rest, with an increase pDrp1s616 . This reduction in mitochondrial respiration was explained through an observed decrease in mitochondrial content (mtDNA:nDNA). Changes in regulators of mitochondrial dynamics indicate an increase in mitochondrial fission driven by a decrease in inner mitochondrial membrane fusion (OPA1) and increased pDrp1s616 . KEY POINTS: Sixty days of -6° head down tilt bed rest leads to significant changes in body composition, exercise capacity and whole-body substrate metabolism. Micronutrient supplementation throughout bed rest did not preserve whole body metabolic changes. Bed rest results in a decrease in skeletal muscle mitochondrial respiratory capacity, mainly as a result of an observed decrease in mitochondrial content. Prolonged bed rest ensues changes in key regulators of mitochondrial dynamics. OPA1 and Drp1 are significantly reduced, with an increase in pDrp1s616 following bed rest indicative of an increase in mitochondrial fission. Given the reduction in mitochondrial content following 60 days of bed rest, the maintenance of regulators of mitophagy in line with the increase in regulators of mitochondrial fission may act to maintain mitochondrial respiration to meet energy demands.
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Astronauts in microgravity experience multi-system deconditioning, impacting their inflight efficiency and inducing dysfunctions upon return to Earth gravity. To fill the sex gap of knowledge in the health impact of spaceflights, we simulate microgravity with a 5-day dry immersion in 18 healthy women (ClinicalTrials.gov Identifier: NCT05043974). Here we show that dry immersion rapidly induces a sedentarily-like metabolism shift mimicking the beginning of a metabolic syndrome with a drop in glucose tolerance, an increase in the atherogenic index of plasma, and an impaired lipid profile. Bone remodeling markers suggest a decreased bone formation coupled with an increased bone resorption. Fluid shifts and muscular unloading participate to a marked cardiovascular and sensorimotor deconditioning with decreased orthostatic tolerance, aerobic capacity, and postural balance. Collected datasets provide a comprehensive multi-systemic assessment of dry immersion effects in women and pave the way for future sex-based evaluations of countermeasures.
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Vuelo Espacial , Ingravidez , Humanos , Femenino , Descondicionamiento Cardiovascular/fisiología , Inmersión , Ingravidez/efectos adversos , Simulación de IngravidezRESUMEN
The role of physical activity (PA) in the regulation of body weight is still a major topic of debate. This may be because studies have essentially focused on the effects of moderate/vigorous PA (MVPA) on body weight while overlooking the other components of PA, namely, light-intensity PA (LPA, daily life activities) and sedentary behaviors (SB, too much sitting). In this review, we will (i) describe the history of changes in PA behaviors that occurred with modernization; (ii) review data from cross-sectional and longitudinal studies that examined the associations between PA, SB, and measures of obesity; (iii) review interventional studies that investigated the effects of changes in PA and SB on body weight and adiposity; and (iv) discuss experimental studies that addressed potential biological mechanisms underlying the effects of PA and SB on weight regulation. Overall recent findings support the importance of considering all components of PA to better understand the regulation of energy balance and suggest an important role for LPA and SB in addition to MVPA on body weight regulation. Longitudinal large-scale rigorous studies are needed to advance our knowledge of the role of PA/SB in combating the obesity epidemic.
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Ejercicio Físico , Conducta Sedentaria , Humanos , Estudios Transversales , Ejercicio Físico/fisiología , Obesidad/prevención & control , Adiposidad , AcelerometríaRESUMEN
OBJECTIVE: Body mass (BM) loss and body composition (BC) changes threaten astronauts' health and mission success. However, the energetic contribution of the exercise countermeasure to these changes has never been investigated during long-term missions. We studied energy balance and BC in astronauts during 6-month missions onboard the International Space Station. METHODS: Before and after at least 3 months in space, BM, BC, total and activity energy expenditure (TEE and AEE) were measured using the doubly labeled water method in 11 astronauts (2011-2017). Physical activity (PA) was assessed by the SensewearPro® activity-device. RESULTS: Three-month spaceflight decreased BM (- 1.20 kg [SE 0.5]; P = 0.04), mainly due to non-significant fat-free mass loss (FFM; - 0.94 kg [0.59]). The decrease in walking time (- 63.2 min/day [11.5]; P < 0.001) from preflight was compensated by increases in non-ambulatory activities (+ 64.8 min/day [18.8]; P < 0.01). Average TEE was unaffected but a large interindividual variability was noted. Astronauts were stratified into those who maintained (stable_TEE; n = 6) and those who decreased (decreased_TEE; n = 5) TEE and AEE compared to preflight data. Although both groups lost similar BM, FFM was maintained and FM reduced in stable_TEE astronauts, while FFM decreased and FM increased in decreased_TEE astronauts (estimated between-group-difference (EGD) in ΔFFMindex [FFMI] 0.87 kg/m2, 95% CI + 0.32 to + 1.41; P = 0.01, ΔFMindex [FMI] - 1.09 kg/m2, 95% CI - 2.06 to - 0.11 kg/m2; P = 0.03). The stable_TEE group had higher baseline FFMI, and greater baseline and inflight vigorous PA than the decreased_TEE group (P < 0.05 for all). ΔFMI and ΔFFMI were respectively negatively and positively associated with both ΔTEE and ΔAEE. CONCLUSION: Both ground fitness and inflight overall PA are associated with spaceflight-induced TEE and BC changes and thus energy requirements. New instruments are needed to measure real-time individual changes in inflight energy balance components.
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Astronautas , Composición Corporal , Humanos , Metabolismo Energético , Ejercicio FísicoRESUMEN
Two randomized placebo-controlled double-blind paralleled trials (42 men in Lyon, 19 women in Lausanne) were designed to test 2 g/day of a grape polyphenol extract during 31 days of high calorie-high fructose overfeeding. Hyperinsulinemic-euglycemic clamps and test meals with [1,1,1-13C3]-triolein were performed before and at the end of the intervention. Changes in body composition were assessed by dual-energy X-ray absorptiometry (DEXA). Fat volumes of the abdominal region and liver fat content were determined in men only, using 3D-magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) at 3T. Adipocyte's size was measured in subcutaneous fat biopsies. Bodyweight and fat mass increased during overfeeding, in men and in women. While whole body insulin sensitivity did not change, homeostasis model assessment of insulin resistance (HOMA-IR) and the hepatic insulin resistance index (HIR) increased during overfeeding. Liver fat increased in men. However, grape polyphenol supplementation did not modify the metabolic and anthropometric parameters or counteract the changes during overfeeding, neither in men nor in women. Polyphenol intake was associated with a reduction in adipocyte size in women femoral fat. Grape polyphenol supplementation did not counteract the moderated metabolic alterations induced by one month of high calorie-high fructose overfeeding in men and women. The clinical trials are registered under the numbers NCT02145780 and NCT02225457 at ClinicalTrials.gov and available at https://clinicaltrials.gov/ct2/show/NCT02145780 and https://clinicaltrials.gov/ct2/show/NCT02225457.
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Some cardiometabolic risk factors such as dyslipidemia and insulin resistance are known to be associated with low gut microbiota richness. A link between gut microbiota richness and the diversity of consumed dietary fibers (DF) has also been reported. We introduced a larger diversity of consumed DF by using a daily consumed bread in subjects at cardiometabolic risk and assessed the impacts on the composition and functions of gut microbiota as well as on cardiometabolic profile. Thirty-nine subjects at cardiometabolic risk were included in a double-blind, randomized, cross-over, twice 8-week study, and consumed daily 150 g of standard bread or enriched with a 7-dietary fiber mixture (5.55 g and 16.05 g of fibers, respectively). Before and after intervention, stool samples were collected for gut microbiota analysis from species determination down to gene-level abundance using shotgun metagenomics, and cardiometabolic profile was assessed. Multi-fiber bread consumption significantly decreased Bacteroides vulgatus, whereas it increased Parabacteroides distasonis, Fusicatenibacter saccharivorans, an unclassified Acutalibacteraceae and an unclassified Eisenbergiella (q < 0.1). The fraction of gut microbiota carrying the gene coding for five families/subfamilies of glycoside hydrolases (CAZymes) were also increased and negatively correlated with peaks and total/incremental area under curve (tAUC/iAUC) of postprandial glycemia and insulinemia. Compared to control bread, multi-fiber bread decreased total cholesterol (-0.42 mM; q < 0.01), LDL cholesterol (-0.36 mM; q < 0.01), insulin (-2.77 mIU/l; q < 0.05), and HOMA (-0.78; q < 0.05). In conclusion, increasing the diversity of DF in a daily consumed product modifies gut microbiota composition and function and could be a relevant nutritional tool to improve cardiometabolic profile.
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Enfermedades Cardiovasculares , Microbioma Gastrointestinal , Pan/análisis , Fibras de la Dieta/análisis , Humanos , MetabolomaRESUMEN
Introduction: Since low body weight is an important determinant of success in many sports such as gymnastics, martial arts and figure skating, athletes can benefit from effective weight loss strategies that preserve muscle mass and athletic performance. The present study investigates the effects of increased protein intake and exogenous ketosis on body composition, energy expenditure, exercise capacity, and perceptions of appetite and well-being during a hypocaloric diet in females. Methods: Thirty-two female recreational athletes (age: 22.2 ± .5 years; body weight: 58.3 ± .8 kg; BMI: 20.8 ± .2 kg·m-2) underwent 4 weeks of 30% caloric restriction and were randomized to receive either an increased daily amount of dietary protein (PROT, â¼2.0-2.2 g protein·kg-1·day-1), 3 × 20 g·day-1 of a ketone ester (KE), or an isocaloric placebo (PLA). Body composition was measured by DXA, resting energy expenditure (REE) by indirect calorimetry, exercise capacity during a VO2max test, appetite hormones were measured in serum, and perceptions of general well-being were evaluated via questionnaires. Results: The hypocaloric diet reduced body weight by 3.8 ± .3 kg in PLA, 3.2 ± .3 kg in KE and 2.4 ± .2 kg in PROT (Ptime<.0001). The drop in fat mass was similar between treatments (average: 2.6 ± .1 kg, Ptime<.0001), while muscle mass was only reduced in PLA and KE (average: .8 ± .2 kg, Ptime<.05), and remained preserved in PROT (Pinteraction<.01). REE [adjusted for lean mass] was reduced after caloric restriction in PLA (pre: 32.7 ± .5, post: 28.5 ± .6 kcal·day-1·kg-1) and PROT (pre: 32.9 ± 1.0, post: 28.4 ± 1.0 kcal·day-1·kg-1), but not in KE (pre: 31.8 ± .9, post: 30.4 ± .8 kcal·day-1·kg-1) (Pinteraction<.005). Furthermore, time to exhaustion during the VO2max test decreased in PLA (by 2.5 ± .7%, p < .05) but not in KE and PROT (Pinteraction<.05). Lastly, the perception of overall stress increased in PLA and PROT (p < .05), but not in KE (Pinteraction<.05). Conclusion: Increased protein intake effectively prevented muscle wasting and maintained exercise capacity during a period of caloric restriction in female recreational athletes. Furthermore, exogenous ketosis did not affect body composition, but showed its potential in weight management by preserving a drop in exercise capacity and REE and by improving overall stress parameters during a period of caloric restriction.
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Physical inactivity, i.e. not reaching the recommended level of physical activity (PA), and sedentary behaviours (SB), i.e. sitting time, have been associated with increased risk for common metabolic diseases. Recent epidemiological data suggest that high volumes of SB are detrimental to metabolic health, even in the presence of regular exercise, i.e. moderate/vigorous PA. This suggests that the health effects of SB are independent from those of exercise. However, experimentally testing this hypothesis is complicated because of the difficulty in disassociating SB from PA. Bedrest studies, a traditional space science model, can offer new insights. In some bedrest studies, an exercise training protocol has been used to counteract the harmful effects of inactivity. While bedrest induces an inactive and sedentary state, exercise with bedrest represents a unique model of sedentary yet physically active people. Here, we review bedrest studies with and without exercise training. Although exercise training prevents the loss of muscle mass and function, even large volumes of exercise are not sufficient to fully counteract the negative metabolic adaptations triggered by inactivity. This observation supports the existence of independent adverse health effects of SB, but also the potential benefits of non-exercise activity, i.e. daily living light PA. We gathered available data to examine the complex relationships between exercise, non-exercise activity, SB and health outcomes. Given the large amount of SB in modern societies, the sole promotion of exercise, i.e. moderate/vigorous PA may be insufficient, and promotion of light PA may be a complimentary approach to improve health.
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Reposo en Cama , Conducta Sedentaria , Ejercicio Físico , HumanosRESUMEN
BACKGROUND: Fasting is attracting an increasing interest as a potential strategy for managing diseases, including metabolic disorders and complementary cancer therapy. Despite concerns of clinicians regarding protein catabolism and muscle loss, evidence-based clinical data in response to long-term fasting in healthy humans are scarce. The objective of this study was to measure clinical constants, metabolic, and muscular response in healthy men during and after a 10 day fast combined with a physical activity programme. METHODS: Sixteen men (44 ± 14 years; 26.2 ± 0.9 kg/m2 ) fasted with a supplement of 200-250 kcal/day and up to 3 h daily low-intensity physical activity according to the peer-reviewed Buchinger Wilhelmi protocol. Changes in body weight (BW) and composition, basal metabolic rate (BMR), physical activity, muscle strength and function, protein utilization, inflammatory, and metabolic status were assessed during the 10 day fast, the 4 days of food reintroduction, and at 3 month follow-up. RESULTS: The 10 day fast decreased BW by 7% (-5.9 ± 0.2 kg, P < 0.001) and BMR by 12% (P < 0.01). Fat mass and lean soft tissues (LST) accounted for about 40% and 60% of weight loss, respectively, -2.3 ± 0.18 kg and -3.53 ± 0.13 kg, P < 0.001. LST loss was explained by the reduction in extracellular water (44%), muscle and liver glycogen and associated water (14%), and metabolic active lean tissue (42%). Plasma 3-methyl-histidine increased until Day 5 of fasting and then decreased, suggesting that protein sparing might follow early proteolysis. Daily steps count increased by 60% (P < 0.001) during the fasting period. Strength was maintained in non-weight-bearing muscles and increased in weight-bearing muscles (+33%, P < 0.001). Glycaemia, insulinemia, blood lipids, and blood pressure dropped during the fast (P < 0.05 for all), while non-esterified fatty acids and urinary beta-hydroxybutyrate increased (P < 0.01 for both). After a transient reduction, inflammatory cytokines returned to baseline at Day 10 of fasting, and LST were still lower than baseline values (-2.3% and -3.2%, respectively; P < 0.05 for both). CONCLUSIONS: A 10 day fast appears safe in healthy humans. Protein loss occurs in early fast but decreases as ketogenesis increases. Fasting combined with physical activity does not negatively impact muscle function. Future studies will need to confirm these first findings.
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Adaptación Fisiológica , Ayuno , Adulto , Ejercicio Físico , Humanos , Masculino , Persona de Mediana Edad , Músculos , Estudios ProspectivosRESUMEN
To investigate mechanisms by which hibernators avoid atherogenic hyperlipidemia during hibernation, we assessed lipoprotein and cholesterol metabolisms of free-ranging Scandinavian brown bears (Ursus arctos). In winter- and summer-captured bears, we measured lipoprotein sizes and sub-classes, triglyceride-related plasma-enzyme activities, and muscle lipid composition along with plasma-levels of antioxidant capacities and inflammatory markers. Although hibernating bears increased nearly all lipid levels, a 36%-higher cholesteryl-ester transfer-protein activity allowed to stabilize lipid composition of high-density lipoproteins (HDL). Levels of inflammatory metabolites, i.e., 7-ketocholesterol and 11ß-prostaglandin F2α, declined in winter and correlated inversely with cardioprotective HDL2b-proportions and HDL-sizes that increased during hibernation. Lower muscle-cholesterol concentrations and lecithin-cholesterol acyltransferase activity in winter suggest that hibernating bears tightly controlled peripheral-cholesterol synthesis and/or release. Finally, greater plasma-antioxidant capacities prevented excessive lipid-specific oxidative damages in plasma and muscles of hibernating bears. Hence, the brown bear manages large lipid fluxes during hibernation, without developing adverse atherogenic effects that occur in humans and non-hibernators.
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Aterosclerosis/prevención & control , Dislipidemias/prevención & control , Hibernación , Ursidae/fisiología , AnimalesRESUMEN
Muscle atrophy arises from a multiplicity of physio-pathological situations and has very detrimental consequences for the whole body. Although knowledge of muscle atrophy mechanisms keeps growing, there is still no proven treatment to date. This study aimed at identifying new drivers for muscle atrophy resistance. We selected an innovative approach that compares muscle transcriptome between an original model of natural resistance to muscle atrophy, the hibernating brown bear, and a classical model of induced atrophy, the unloaded mouse. Using RNA sequencing, we identified 4415 differentially expressed genes, including 1746 up- and 2369 down-regulated genes, in bear muscles between the active versus hibernating period. We focused on the Transforming Growth Factor (TGF)-ß and the Bone Morphogenetic Protein (BMP) pathways, respectively, involved in muscle mass loss and maintenance. TGF-ß- and BMP-related genes were overall down- and up-regulated in the non-atrophied muscles of the hibernating bear, respectively, and the opposite occurred for the atrophied muscles of the unloaded mouse. This was further substantiated at the protein level. Our data suggest TGF-ß/BMP balance is crucial for muscle mass maintenance during long-term physical inactivity in the hibernating bear. Thus, concurrent activation of the BMP pathway may potentiate TGF-ß inhibiting therapies already targeted to prevent muscle atrophy.
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Proteínas Morfogenéticas Óseas/metabolismo , Hibernación , Atrofia Muscular/metabolismo , Músculo Cuádriceps/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Ursidae/metabolismo , Animales , Proteínas Morfogenéticas Óseas/genética , Modelos Animales de Enfermedad , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Suspensión Trasera , Masculino , Ratones , Ratones Endogámicos C57BL , Atrofia Muscular/genética , Atrofia Muscular/patología , Músculo Cuádriceps/patología , RNA-Seq , Transducción de Señal , Factores de Tiempo , Transcriptoma , Factor de Crecimiento Transformador beta/genética , Ursidae/genéticaRESUMEN
A post hoc analysis of the Diabeloop WP7 multicentre, randomized controlled trial was performed to investigate the efficacy of the Diabeloop Generation-1 (DBLG1) closed-loop system in controlling the hypoglycaemia induced by physical activity (PA) in real-life conditions. Glycaemic outcomes were compared between days with and without PA in 56 patients with type 1 diabetes (T1D) using DBLG1 for 12 weeks. After the patient announces a PA, DBLG1 reduces insulin delivery and, if necessary, calculates the amount of preventive carbohydrates (CHO). Daily time spent in the interstitial glucose range less than 70 mg/dL was not significantly different between days with and without PA (2.0% ± 1.5% vs. 2.2% ± 1.1%), regardless of the intensity or duration of the PA. Preventive CHO intake recommended by the system was significantly higher in days with PA (41.1 ± 35.5 vs. 21.8 ± 28.5 g/day; P < .0001), and insulin delivery was significantly lower (31.5 ± 10.5 vs. 34.0 ± 10.5 U/day; P < .0001). The time spent in hyperglycaemia and the glycaemic variation coefficient increased significantly on days with PA. In real-life conditions, the use of DBLG1 avoids PA-induced hypoglycaemia. Insulin adjustments and preventive CHO recommendation may explain this therapeutic benefit.
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Diabetes Mellitus Tipo 1 , Hipoglucemia , Glucemia , Estudios Cruzados , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Dieta , Ejercicio Físico , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Sistemas de Infusión de InsulinaRESUMEN
In small hibernators, global downregulation of the endocannabinoid system (ECS), which is involved in modulating neuronal signaling, feeding behavior, energy metabolism, and circannual rhythms, has been reported to possibly drive physiological adaptation to the hibernating state. In hibernating brown bears (Ursus arctos), we hypothesized that beyond an overall suppression of the ECS, seasonal shift in endocannabinoids compounds could be linked to bear's peculiar features that include hibernation without arousal episodes and capacity to react to external disturbance. We explored circulating lipids in serum and the ECS in plasma and metabolically active tissues in free-ranging subadult Scandinavian brown bears when both active and hibernating. In winter bear serum, in addition to a 2-fold increase in total fatty acid concentration, we found significant changes in relative proportions of circulating fatty acids, such as a 2-fold increase in docosahexaenoic acid C22:6 n-3 and a decrease in arachidonic acid C20:4 n-6. In adipose and muscle tissues of hibernating bears, we found significant lower concentrations of 2-arachidonoylglycerol (2-AG), a major ligand of cannabinoid receptors 1 (CB1) and 2 (CB2). Lower mRNA level for genes encoding CB1 and CB2 were also found in winter muscle and adipose tissue, respectively. The observed reduction in ECS tone may promote fatty acid mobilization from body fat stores, and favor carbohydrate metabolism in skeletal muscle of hibernating bears. Additionally, high circulating level of the endocannabinoid-like compound N-oleoylethanolamide (OEA) in winter could favor lipolysis and fatty acid oxidation in peripheral tissues. We also speculated on a role of OEA in the conservation of an anorexigenic signal and in the maintenance of torpor during hibernation, while sustaining the capacity of bears to sense stimuli from the environment.
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INTRODUCTION: The COVID-19 pandemic caused by SARS-CoV-2 threatens global public health, and there is an urgent public health need to assess acquired immunity to SARS-CoV-2. Serological tests might provide results that can be complementary to or confirm suspected COVID-19 cases and reveal previous infection. The performance of serological assays (sensitivity and specificity) has to be evaluated before their use in the general population. The neutralisation capacity of the produced antibodies also has to be evaluated. METHODS AND ANALYSIS: We set up a prospective, multicentric clinical study to evaluate the performance of serological kits among a population of healthcare workers presenting mild symptoms suggestive of SARS-CoV-2 infection. Four hundred symptomatic healthcare workers will be included in the COVID-SER study. The values obtained from a control cohort included during the prepandemic time will be used as reference. A workflow was set up to study serological response to SARS-CoV-2 infection and to evaluate antibody neutralisation capacity in patients with a confirmed SARS-CoV-2 infection. The sensitivity and specificity of the tests will be assessed using molecular detection of the virus as a reference. The measurement of IgM and IgG antibodies will be performed once per week for 6 consecutive weeks and then at 6, 12, 18, 24 and 36 months after the diagnosis. The kinetics of IgM and IgG will determine the optimal period to perform serological testing. The proportion of false negative PCR tests in symptomatic subjects will be determined on the basis of subsequent seroconversions. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the national review board for biomedical research in April 2020 (Comité de Protection des Personnes Sud Méditerranée I, Marseille, France) (ID RCB 2020-A00932-37). Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04341142.
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Anticuerpos Antivirales/análisis , COVID-19/diagnóstico , Tamizaje Masivo/métodos , Pandemias , SARS-CoV-2/inmunología , COVID-19/epidemiología , Femenino , Humanos , Masculino , Estudios Prospectivos , Pruebas SerológicasRESUMEN
BACKGROUND: Despite an increasing number of studies highlighting the health benefits of community gardening, the literature is limited by cross-sectional designs. The "JArDinS" quasi-experimental study aimed to assess the impact of community garden participation on the adoption of more sustainable lifestyles among French adults. METHODS: Individuals entering a community garden in Montpellier (France) in 2018 (n = 66) were compared with pairwise matched individuals with no experience in community gardening (n = 66). Nutritional quality, environmental impact and cost of monthly household food supplies, level of physical activity measured by accelerometers, as well as mental and social well-being, sensitivity to food waste, and connection with nature were evaluated at baseline (t0) and 12 months later (t1) to explore sustainability of lifestyles in social/health, environmental and economic dimensions. Linear mixed models were used to determine the independent effect of community gardening on investigated lifestyles components. In-depth interviews were conducted at t1 with 15 gardeners to better understand changes that may have occurred in gardeners' lives during the first year of gardening. RESULTS: At t0, gardeners had lower education level, lower BMI and their household reported lower percentage of meals consumed outside of the home compared to non-gardeners (p < 0.05). Participating in the community garden had no significant impact, in spite of sufficient statistical power, on fruit and vegetables supplies (main outcome), nor on physical activity parameters, nor on others of the social/health, environmental and economic lifestyles components investigated. Qualitative interviews suggested the existence of pre-established health and environmental consciousness in some gardeners and revealed several barriers to the participation such as lack of time, lack of gardening knowledge, physical difficulty of gardening, health problems and conflicts with other gardeners. CONCLUSIONS: The health benefits of community gardening previously reported by cross-sectional studies might be confounded by selection bias. The JArDinS study highlights the need to identify solutions to overcome barriers related to community garden participation when designing relevant public health interventions for the promotion of sustainable lifestyles. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov as NCT03694782 . Date of registration: 3rd October 2018, retrospectively registered.