Laboratoire de Biologie de l'Exercice pour la Performance et la Santé

OBJECTIVE To analyze safety and efficacy of the Diabeloop Generation 1 (DBLG1) hybrid closed-loop artificial pancreas system in patients with type 1 diabetes in real-world conditions. RESEARCH DESIGN AND METHODS After a 1-week run-in period with their usual pump, 25 patients were provided the commercial DBLG1 system. The results are presented on time in range (TIR) and HbA1c over 6 months. RESULTS The mean (SD; range) age of patients was 43 (13.8; 25–72) years. At baseline, the mean HbA1c and TIR 70–180 mg/dL were, respectively, 7.9% (0.93; 5.6–8.5%) [63 mmol/mol (10; 38–69 mmol/mol)] and 53% (16.4; 21–85%). One patient stopped using the system after 2 months. At 6 months, the mean HbA1c decreased to 7.1% [54 mmol/mol] (P < 0.001) and TIR 70–180 mg/dL increased to 69.7% (P < 0.0001). TIR <70 mg/dL decreased from 2.4 to 1.3% (P = 0.03), and TIR <54 mg/dL decreased from 0.32 to 0.24% (P = 0.42). No serious adverse event was reported during the study. CONCLUSIONS The ability of the DBLG1 system to significantly improve glycemic control in real-world conditions, without serious adverse events, was confirmed in this follow-up study.

BACKGROUND: Time in range (TIR) goals are rarely met in children with type 1 diabetes, except at the cost of increased hypoglycaemia episodes. Our objective was to evaluate the safety and efficiency of the Diabeloop DBL4K (Diabeloop, Grenoble, France) hybrid closed-loop system in prepubescent children. METHODS: 9% (75 mmol/mol) or less, and insulin pump treatment for at least 3 months. Participants were randomly assigned (1:1) to a closed-loop device or sensor-augmented pump (open loop) therapy. Randomisation was by a permuted block randomisation scheme, using an interactive web-based response system, and was stratified on centre (block size 6). The assessed closed-loop device, the Diabeloop for Kids DBL4K hybrid closed-loop system, is an automated blood glucose regulation system composed of a handset, insulin pump, and continuous glucose monitor. The open-loop system is defined as a sensor-augmented pump therapy composed of the usual insulin pump used by the patient and a continuous glucose monitor. A 72-h in-patient period was followed by a 6-week home phase. After a 1-week washout period, the participants crossed over to the other device. The primary outcome, assessed in the intention-to-treat population, was the mean proportion of time spent in hypoglycaemia (3·9 mmol/L [<70 mg/dL]) during the hospital phase, with a non-inferiority margin of -2·5% (absolute value). Safety was assessed in the intention-to-treat population on a per-protocol basis. This study was registered with ClinicalTrials.gov, NCT03671915. FINDINGS: Between May 6 and Dec 23, 2019, we included 21 participants (closed loop then open loop, n=10; open loop then closed loop, n=11). The proportion of time spent in hypoglycaemia was significantly lower with the closed-loop system than the open-loop system in both groups (2·04% [95% CI 0·44 to 3·64] vs 7·06% [5·46 to 8·66]; non-inferiority one-sided p<0·0001). No severe ketoacidosis, nor severe hyoglycaemic events or fatal adverse events occurred. All 25 adverse events (18 with the closed-loop system, seven with the open-loop system) were related to the treatment. INTERPRETATION: The closed-loop Diabeloop system decreased hypoglycaemic episodes and provided good metabolic control in prepubescent children with type 1 diabetes, under real-life conditions. This finding supports the safe use of closed-loop technology in this paediatric population. FUNDING: Diabeloop. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

PURPOSE: The aim of this review was to (1) characterize the time-course of markers of exercise-induced muscle damage (EIMD) based on the level of maximal voluntary contraction torque loss at 24-48h post-exercise (MVCloss24-48h), (2) identify factors (e.g., exercise and population characteristics) affecting the level of MVCloss24-48h, and (3) evaluate the appropriateness of EIMD markers as indicators of MVCloss24-48h. METHODS: Magnitude of change of each EIMD markers was normalized using the standardized mean differences method to compare the results from different studies. Time-course of EIMD markers were characterized according to three levels of MVCloss24-48h based on a clustering analysis of the 141 studies included. Association between MVCloss24-48h levels and participant´s characteristics or exercise type/modalities were assessed. Meta-regressions were performed to investigate the associations between MVCloss24-48h and EIMD markers changes at <6h, 24h, 48h, 72h and >96h after exercise. RESULTS: Time-course of EIMD markers recovery differs between levels of MVCloss24-48h. Training status and exercise type/modality were associated with MVCloss24-48h level (p<0.05). MVCloss24-48h was correlated to changes in myoglobin concentration (<6h), jump height (24h) and range of motion (48h) (p<0.001). CONCLUSION: As the exercise could differently affect markers as function of the EIMD severity (i.e., MVCloss24-48h levels), different markers should be used as function of the timing of measurement. Mb concentration should be used during the first hours after the exercise (<6h), whereas jump height (24h) and range of motion (48h) could be used as surrogate for maximal voluntary contraction later. Moreover, training status and exercise type/modality could influence the magnitude of MVCloss24-48h.

The aims of this study were to 1) determine the key load indicators in professional soccer through principal component analysis (PCA); and 2) analyse the load variability of each training and match day within the microcycle considering the principal components. Data from 111 load variables were collected using tracking systems in both training and match days (MD). The results showed that 7 variables, which belonged to the first two components of the PCA, explained 80.3% of total variance. Specifically, these variables were Metabolic power, total of steps, Fourier transform (FFT) duration, deceleration distance covered (2–3 m/s2), total of running actions (12–18 km/h; 21–24 km/h), and distance covered (6–12 km/h). Regarding the analysis of the load variability of each training and match day within the microcycle, the lowest load variability was observed in −1MD. Also, a great load variability in +1MD with significant differences compared to −5MD (p<0.001; d=0.49) and −4MD (p=0.01; d=0.26) was found. This study suggests the use of the PCA in the context of team sports to reduce the large number of variables, which are daily managed by strength and conditioning coaches, in addition to the analysis of load variability of each training and match day within the microcycle.

Background: The neuromuscular system is able to quickly adapt to exercise-induced muscle damage (EIMD), such that it is less affected by subsequent damaging exercise, a phenomenon known as the repeated bout effect (RBE). The objective was to determine whether the mechanical properties of the quadriceps, as evaluated by shear wave elastography (SWE), were less affected when a second bout of eccentric-biased exercise was performed 2 weeks later. It was hypothesized that the first bout would confer protection against extensive muscle damage through an adaptation of the muscle stiffness before the second bout (i.e., higher muscle stiffness). Methods: Sixteen males performed two identical bouts of downhill walking separated by 2 weeks (45 min at 4.5 km.h −1 ; gradient: 25%; load: 30% of the body mass). Rectus femoris (RF) and vastus lateralis (VL) resting shear elastic modulus (µ) and EIMD symptoms were measured before and up to 7 days following the exercise bouts. Changes in neuromuscular function was evaluated by maximal voluntary contraction torque, voluntary activation level, evoked mechanical response to single and double (10 and 100 Hz doublets) electrical stimulation. An index of protection (IP) was calculated for EIMD symptoms to assess magnitude the RBE. Results: EIMD symptoms were less affected after the second than the first exercise bout. RF and VL-µ increased ( p &amp;lt; 0.001) only after the first exercise. RF µ was elevated up to 2 weeks after the end of the first exercise ( p &amp;lt; 0.001) whereas VL µ was only increased up to 24 h. The increase in µ observed 2 weeks after the end of the first exercise was correlated with the IP; i.e., attenuation of alterations in muscle µ, 10 Hz-doublet amplitude and rate of torque development after the second exercise bout ( p &amp;lt; 0.05). Conclusion: We showed that muscle µ assessed by SWE was sensitive to the RBE, with a differential effect between VL and RF. The persistent increase in µ was associated with the attenuation of neuromuscular impairments observed after the second bout, suggesting that the increased muscle stiffness could be a “protective” adaptation making muscles more resistant to the mechanical strain associated to eccentric contractions.

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.

Michael Quiquempoix,1,2 Fabien Sauvet,1,2 Mégane Erblang,1– 3 Pascal Van Beers,1,2 Mathias Guillard,1,2 Catherine Drogou,1,2 Aurélie Trignol,1,2 Anita Vergez,1,2 Damien Léger,2,4 Mounir Chennaoui,1,2 Danielle Gomez-Merino,1,2 Arnaud Rabat1,2 1Department of Operational Environments, Fatigue and Vigilance Team, French Armed Forces Biomedical Research Institute (IRBA), Paris, France; 2VIFASOM Team (EA 7330), University of Paris - Hôtel Dieu AP-HP Hospital, Paris, France; 3LBEPS, Univ Evry, IRBA, University of Paris-Saclay, Paris, France; 4Centre du sommeil et de la vigilance, Hôpital Hôtel Dieu AP-HP, Paris, 75004, FranceCorrespondence: Michael Quiquempoix, Department of operational environments, Fatigue and Vigilance Team, Armed Forces Biomedical Research Institute (IRBA), 1, avenue du Général Valérie André, BP 73, Brétigny sur Orge, Paris, 91223, France, Email michael.quiquempoix@def.gouv.frIntroduction: It is widely admitted that both total sleep deprivation (TSD) and extended task engagement (Time-On-Task, TOT) induce a cognitive fatigue state in healthy subjects. Even if EEG theta activity and adenosine both increase with cognitive fatigue, it remains unclear if these modifications are common mechanisms for both sustained attention and executive processes.Methods: We performed a double-blind counter-balanced (placebo (PCBO) and caffeine (CAF) - 2× 2.5 mg/kg/24 h)) study on 24 healthy subjects (33.7 ± 5.9 y). Subjects participated in an experimental protocol including an habituation/training day followed by a baseline day (D0 and D1) and a total sleep deprivation (TSD) day beginning on D1 at 23:00 until D2 at 21:00. Subjects performed the psychomotor vigilance test (PVT) assessing sustained attention, followed by the executive Go-NoGo inhibition task and the 2-NBack working memory task at 09:15 on D1 and D2.Results: We showed differential contributions of TSD and TOT on deficits in sustained attention and both executive processes. An alleviating effect of caffeine intake is only observed on sustained attention deficits related to TSD and not at all on TOT effect. The caffeine dose slows down the triggering of sustained attention deficits related to TOT effect.Discussion: These results suggest that sustained attention deficits induced by TSD rely on the adenosinergic mechanism whereas TOT effect observed for both sustained attention and executive would not.Keywords: total sleep deprivation, time on task, caffeine, sustained attention, inhibition, working memory, cognitive fatigue, mental fatigue, healthy subjects

Background: Obesity is a major public health problem of our time as a risk factor for cardiometabolic disease and the available pharmacological tools needed to tackle the obesity pandemic are insufficient. Neurotensin (NTS) is a 13 amino acid peptide, which is derived from a larger precursor hormone called proneurotensin or Long Form NTS (LF NTS). NTS modulates neuro-transmitter release in the central system nervous, and facilitates intestinal fat absorption in the gastrointestinal tract. Mice lacking LF NTS are protected from high fat diet (HFD) induced obesity, hepatic steatosis and glucose intolerance. In humans, increased levels of LF NTS strongly and independently predict the development of obesity, diabetes mellitus, cardiovascular disease and mortality. With the perspective to develop therapeutic tools to neutralize LF NTS, we developed a monoclonal antibody, specifically inhibiting the function of the LF NTS (LF NTS mAb). This antibody was tested for the effects on body weight, metabolic parameters and behavior in mice made obese by high-fat diet. Methods: C57bl/6j mice were subjected to high-fat diet (HFD) until they reached an obesity state, then food was switched to chow. Mice were treated with either PBS (control therapy) or LF NTS mAb at the dose of 5 mg/kg once a week (i.v.). Mice weight, plasma biochemical analysis, fat and muscle size and distribution and behavioral tests were performed during the losing weight period and the stabilization period. Results: Obese mice treated with the LF NTS mAb lost weight significantly faster than the control treated group. LF NTS mAb treatment also resulted in smaller fat depots, increased fecal cholesterol excretion, reduced liver fat and larger muscle fiber size. Moreover, mice on active therapy were also less stressed, more curious and more active, providing a possible explanation to their weight loss. Conclusion: Our results demonstrate that in mice subjected to HFD-induced obesity, a blockade of LF NTS with a monoclonal antibody results in reduced body weight, adipocyte volume and increased muscle fiber size, possibly explained by beneficial effects on behavior. The underlying mechanisms as well as any future role of LF NTS mAb as an anti-obesity agent warrants further studies.

(1) Background: Caffeine is a psychostimulant that is well known to mitigate the deleterious effects of sleep debt. Our aim was to assess the effects of acute caffeine intake on cognitive vulnerability and brain activity during total sleep deprivation (TSD), taking into account habitual caffeine consumption. (2) Methods: Thirty-seven subjects were evaluated in a double-blind, crossover, total sleep deprivation protocol with caffeine or placebo treatment. Vigilant attention was evaluated every six hours during TSD using the psychomotor vigilance test (PVT) with EEG recordings. The influence of habitual caffeine consumption was analyzed by categorizing subjects into low, moderate, and high consumers. (3) Results: The PVT reaction time (RT) increased during TSD and was lower in the caffeine condition vs. the placebo condition. The RT was shorter in the low-caffeine consumers compared to moderate and high consumers, regardless of conditions and treatments. The TSD-related increase in EEG power was attenuated by acute caffeine intake independently of habitual caffeine consumption, and the individual alpha frequency (IAF) was lower in the high-consumption group. The IAF was negatively correlated with daytime sleepiness. Moreover, a correlation analysis showed that the higher the daily caffeine consumption, the higher the RT and the lower the IAF. (4) Conclusions: A high level of habitual caffeine consumption decreases attentional performance and alpha frequencies, decreasing tolerance to sleep deprivation.

OBJECTIVE: Human functional genomics has proven powerful in discovering drug targets for common metabolic disorders. Through this approach, we investigated the involvement of the purinergic receptor P2RY1 in type 2 diabetes (T2D). METHODS: P2RY1 was sequenced in 9,266 participants including 4,177 patients with T2D. In vitro analyses were then performed to assess the functional effect of each variant. Expression quantitative trait loci (eQTL) analysis was performed in pancreatic islets from 103 pancreatectomized individuals. The effect of P2RY1 on glucose-stimulated insulin secretion was finally assessed in human pancreatic beta cells (EndoCβH5), and RNA sequencing was performed on these cells. RESULTS: Sequencing P2YR1 in 9,266 participants revealed 22 rare variants, seven of which were loss-of-function according to our in vitro analyses. Carriers, except one, exhibited impaired glucose control. Our eQTL analysis of human islets identified P2RY1 variants, in a beta-cell enhancer, linked to increased P2RY1 expression and reduced T2D risk, contrasting with variants located in a silent region associated with decreased P2RY1 expression and increased T2D risk. Additionally, a P2RY1-specific agonist increased insulin secretion upon glucose stimulation, while the antagonist led to decreased insulin secretion. RNA-seq highlighted TXNIP as one of the main transcriptomic markers of insulin secretion triggered by P2RY1 agonist. CONCLUSION: Our findings suggest that P2RY1 inherited or acquired dysfunction increases T2D risk and that P2RY1 activation stimulates insulin secretion. Selective P2RY1 agonists, impermeable to the blood-brain barrier, could serve as potential insulin secretagogues.

Purpose: The purpose of this study was to evaluate the effect of pre-exercise alkalosis, induced via ingestion of sodium bicarbonate, on changes to lactate/pH regulatory proteins and mitochondrial function induced by a sprint-interval exercise session in humans. Methods: On two occasions separated by 1 week, eight active men performed a 3 × 30-s all-out cycling test, interspersed with 20 min of recovery, following either placebo (PLA) or sodium bicarbonate (BIC) ingestion. Results: Blood bicarbonate and pH were elevated at all time points after ingestion in BIC vs PLA ( p &amp;lt; 0.05). The protein content of monocarboxylate transporter 1 (MCT1) and basigin (CD147), at 6 h and 24 h post-exercise, and sodium/hydrogen exchanger 1 (NHE1) 24 h post-exercise, were significantly greater in BIC compared to PLA ( p &amp;lt; 0.05), whereas monocarboxylate transporter 4 (MCT4), sodium/bicarbonate cotransporter (NBC), and carbonic anhydrase isoform II (CAII) content was unchanged. These increases in protein content in BIC vs. PLA after acute sprint-interval exercise may be associated with altered physiological responses to exercise, such as the higher blood pH and bicarbonate concentration values, and lower exercise-induced oxidative stress observed during recovery ( p &amp;lt; 0.05). Additionally, mitochondrial respiration decreased after 24 h of recovery in the BIC condition only, with no changes in oxidative protein content in either condition. Conclusion: These data demonstrate that metabolic alkalosis induces post-exercise increases in several lactate/pH regulatory proteins, and reveal an unexpected role for acidosis in mitigating the loss of mitochondrial respiration caused by exercise in the short term.

The neuromuscular system can quickly adapt to exercise-induced muscle damage (EIMD), such that it is less affected by subsequent damaging exercise, a phenomenon known as the repeated bout effect (RBE). Circulating muscle-specific microRNAs (myomiRs) may be able to potentially predict the long-lasting maximal voluntary contraction (MVC) torque deficit (&gt;24 h), an indicator of EIMD. We aimed to investigate: 1) how plasma myomiR levels are modified by the RBE and 2) whether plasma myomiRs can predict the long-lasting MVC torque deficit. Nineteen participants performed two identical bouts of loaded downhill walking separated by 2 wk. MVC torque, creatine kinase (CK) activity, myoglobin (Mb) concentration, and myomiR levels were measured before and up to 48 h after exercise. Correlation and multiple regression analyses were performed to assess the ability of these markers to predict the largest MVC torque loss beyond 24 h postexercise. Similar to MVC torque, CK activity, and the Mb concentration, the relative abundance of certain myomiRs (hsa-miR-1-3p, and hsa-miR-133a-3p) was less affected after the second bout of exercise relative to the first bout. The CK activity, Mb concentration, and level of several myomiRs (hsa-miR-1-3p, hsa-miR-133a-3p, and hsa-miR-206) correlated with long-lasting MVC torque loss. Multiple regression showed that the best combination of markers to predict the long-lasting deficit of MVC torque included several myomiRs, Mb, and CK. Certain myomiR levels increased less after exercise bout 2 than after exercise bout 1, indicating the presence of the RBE. The measurement of myomiR levels in combination with Mb concentrations and CK activity could improve the prediction of the long-lasting MVC torque deficit.

Altitude camps are used during the preparation of endurance athletes to improve performance based on the stimulation of erythropoiesis by living at high altitude. In addition to such whole-body adaptations, studies have suggested that high-altitude training increases mitochondrial mass, but this has been challenged by later studies. Here, we hypothesized that living and training at high altitude (LHTH) improves mitochondrial efficiency and/or substrate utilization. Female rats were exposed and trained in hypoxia (simulated 3,200 m) for 5 weeks (LHTH) and compared to sedentary rats living in hypoxia (LH) or normoxia (LL) or those that trained in normoxia (LLTL). Maximal aerobic velocity (MAV) improved with training, independently of hypoxia, whereas the time to exhaustion, performed at 65% of MAV, increased both with training ( P = 0.009) and hypoxia ( P = 0.015), with an additive effect of the two conditions. The distance run was 7.98 ± 0.57 km in LHTH vs. 6.94 ± 0.51 in LLTL (+15%, ns). The hematocrit increased &amp;gt;20% with hypoxia ( P &amp;lt; 0.001). The increases in mitochondrial mass and maximal oxidative capacity with endurance training were blunted by combination with hypoxia (−30% for citrate synthase, P &amp;lt; 0.01, and −23% for Vmax glut−succ , P &amp;lt; 0.001 between LHTH and LLTL). A similar reduction between the LHTH and LLTL groups was found for maximal respiration with pyruvate (−29%, P &amp;lt; 0.001), for acceptor-control ratio (−36%, hypoxia effect, P &amp;lt; 0.001), and for creatine kinase efficiency (−48%, P &amp;lt; 0.01). 3-hydroxyl acyl coenzyme A dehydrogenase was not altered by hypoxia, whereas maximal respiration with Palmitoyl-CoA specifically decreased. Overall, our results show that mitochondrial adaptations are not involved in the improvement of submaximal aerobic performance after LHTH, suggesting that the benefits of altitude camps in females relies essentially on other factors, such as the transitory elevation of hematocrit, and should be planned a few weeks before competition and not several months.

BACKGROUND: Iodine supplementation is indicated by the French National Authority for Health (HAS) and the World Health Organization (WHO) during pregnancy. This study investigates whether this supplementation is consistently prescribed in line with WHO recommendations in pregnant women diagnosed with gestational diabetes mellitus. METHOD: A total of 99 women with a diagnosis of gestational diabetes were included in the study and were all closely monitored. RESULTS: Only 17 (17.2%) patients received the recommended iodine supplementation. The follow-up, whether conducted by a gynecologist or midwife, did not influence the prescription of iodine supplements. By contrast, 72 (72.7%) of patients received folic acid supplementation. CONCLUSIONS: The prescription of iodine supplementation for the pregnant women included in our study is insufficient. Few practitioners seem aware of the recommendations, even when the pregnancy is complicated by gestational diabetes.

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The RANKL-GLYC study aims to explore the impact of the rapid correction of chronic hyperglycemia on the receptor activator of nuclear factor-kappa B ligand (RANKL) and its antagonist osteoprotegerin (OPG). RANKL and OPG are considered the main factors in the pathophysiology of Charcot neuroarthropathy, a devastating complication of the joints that remains poorly understood. The study began recruiting patients in September 2021 and ends in June 2022; the final study results are scheduled for January 2023.

INTRODUCTION: Genes encoding catechol-O-methyl-transferase (COMT) and adenosine A2A receptor (ADORA2A) have been shown to influence cognitive performances and responses to caffeine intake during prolonged wakefulness. The rs4680 single-nucleotide polymorphism (SNP) of COMT differentiates on memory score and circulating levels of the neurotrophic factor IGF-1. This study aimed to determine the kinetics of IGF-1, testosterone, and cortisol concentrations during prolonged wakefulness under caffeine or placebo intake in 37 healthy participants, and to analyze whether the responses are dependent on COMT rs4680 or ADORA2A rs5751876 SNPs. METHODS: In caffeine (2.5 mg/kg, twice over 24 h) or placebo-controlled condition, blood sampling was performed at 1 h (08:00, baseline), 11 h, 13 h, 25 h (08:00 next day), 35 h, and 37 h of prolonged wakefulness, and at 08:00 after one night of recovery sleep, to assess hormonal concentrations. Genotyping was performed on blood cells. RESULTS: Results indicated a significant increase in IGF-1 levels after 25, 35, and 37 h of prolonged wakefulness in the placebo condition, in subjects carrying the homozygous COMT A/A genotype only (expressed in absolute values [±SEM]: 118 ± 8, 121 ± 10, and 121 ± 10 vs. 105 ± 7 ng/mL for A/A, 127 ± 11, 128 ± 12, and 129 ± 13 vs. 120 ± 11 ng/mL for G/G, and 106 ± 9, 110 ± 10, and 106 ± 10 vs. 101 ± 8 ng/mL for G/A, after 25, 35, and 37 h of wakefulness versus 1 h; p &lt; 0.05, condition X time X SNP). Acute caffeine intake exerted a COMT genotype-dependent reducing effect on IGF-1 kinetic response (104 ± 26, 107 ± 27, and 106 ± 26 vs. 100 ± 25 ng/mL for A/A genotype, at 25, 35, and 37 h of wakefulness vs. 1 h; p &lt; 0.05 condition X time X SNP), plus on resting levels after overnight recovery (102 ± 5 vs. 113 ± 6 ng/mL) (p &lt; 0.05, condition X SNP). Testosterone and cortisol concentrations decreased during wakefulness, and caffeine alleviated the testosterone reduction, unrelated to the COMT polymorphism. No significant main effect of the ADORA2A SNP was shown regardless of hormonal responses. CONCLUSION: Our results indicated that the COMT polymorphism interaction is important in determining the IGF-1 neurotrophic response to sleep deprivation with caffeine intake (NCT03859882).

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