Impact du diabète de type 1 et des niveaux élevés d'hémoglobine glyquée sur l'oxygénation musculaire et cérébrale à l'exercice : répercutions sur l'aptitude physique aérobie

This study sought to investigate whether type 1 diabetes and high levels of glycated hemoglobin (HbA1c) influence oxygen supply including alveolar capillary diffusion, oxygen delivery and release, to active muscle and prefrontal cortex during maximal exercise. We first studied the effect of high level of HbA1c on oxyhemoglobin dissociation at the active muscle measured by Near Infra-Red Spectroscopy (NIRS) during maximal exercise. We found that alveolar capillary diffusion and arterial oxygen content was comparable between patients with type 1 diabetes and healthy subjects. However, patients with inadequate glycemic control but without any clinically detectable vascular complications displayed an impaired aerobic capacity as well as a reduction in blood volume and a dramatic impairment in deoxyhemoglobin (HHb) increase in active skeletal muscle during intense exercise. The latter supports the hypotheses of an increase in O2 affinity induced by hemoglobin glycation and/or of a disturbed balance between nutritive and nonnutritive muscle blood flow. Furthermore, reduced exercise muscle blood volume in poorly controlled patients may warn clinicians of microvascular dysfunction occurring even before overt microangiopathy (Study 1). Secondly, we aimed at investigating prefrontal cortex hemodynamic during an incremental maximal exercise in patients with uncomplicated type 1 diabetes, taking into account chronic glycemic control. We observed that levels and changes in regional cerebral blood volume – as reflected by change in total hemoglobin – were lower at high intensities of exercise in patients with inadequate glycemic control (Study 2).In summary, the physiological stimulus of maximal exercise coupled with NIRS measurement highlighted subclinical disorders of both cerebral hemodynamic and muscle oxygenation in poorly-controlled patients with type 1 diabetes albeit free from any clinical microangiopathy.L’objectif général de ce travail était d’évaluer l’effet du diabète de Type 1 et de l’hyperglycémie chronique (reflétée par un niveau élevé d’HbA1c), chez des patients indemnes de complications micro et macrovasculaires, sur la disponibilité en oxygène (O2) au niveau musculaire et cortical et ses répercussions sur l’aptitude physique aérobie. Dans un premier temps, nous nous sommes attardés à étudier l’effet du diabète et des niveaux élevés d’HbA1c sur les différentes étapes de la cascade d’oxygène (à savoir la diffusion alvéolo-capillaire, le transport artériel et la libération de l’O2 au niveau musculaire) ainsi que sur l’oxygénation musculaire estimée par la Spectroscopie dans le proche Infra-Rouge (NIRS) durant un exercice incrémental et voir les répercussions possibles sur la consommation maximale d’oxygène (〖V ̇O〗_2max). Nous avons montré que les patients DT1 présentent une capacité de diffusion alvéolo-capillaire ainsi qu’une capacité de transport artériel d’O2 comparable aux sujets sains. En revanche, les patients ayant un niveau élevé d’HbA1c présentent une altération de 〖V ̇O〗_2max ainsi qu’une réduction du volume sanguin musculaire (reflétée par une baisse de l’hémoglobine totale) et une nette baisse de la déoxyhémoglobine (HHb) au niveau du muscle actif aux intensités proches de l’exercice maximal. Ce dernier résultat pourrait s’expliquer par l’affinité plus importante de HbA1c pour l’O2 et/ou une altération de la redistribution de débit sanguin entre les vaisseaux nutritifs et non nutritifs. L’altération du volume sanguin au niveau musculaire chez les patients présentant un mauvais contrôle glycémique peut prévenir les cliniciens du dysfonctionnement de la microcirculation survenant avant même qu’une microangiopathie se manifeste à l’état clinique (Étude 1). Dans un second temps, nous nous sommes intéressés à la fonction cérébrale. Notre objectif étant d’évaluer l’hémodynamique cérébrale durant un exercice incrémental maximal. Nous avons trouvé une altération de l’hémodynamique cérébrale (baisse de l’hémoglobine totale) aux intensités proches de l’exercice maximal chez les patients DT1 qui présentent un mauvais contrôle glycémique (Étude 2). Ces deux travaux nous montrent bien que les sujets diabétiques de type 1 indemnes des complications micro et/ou marcovasculaires présentent une faible aptitude physique aérobie qui peut s’expliquer à la fois par une altération de l’oxygénation musculaire et cérébrale. Ces études mettent également en évidence l’intérêt d’associer la NIRS avec un exercice maximal. Ce dernier place les tissus en situation de besoin maximal en O2 ce qui permet de mettre en exergue des altérations fonctionnelles de la microcirculation avant même l’apparition de complications microvasculaires détectables par les tests cliniques habituels

The effect of type 1 diabetes and high levels of glycated hemoglobinon on muscle and cerebral hemodynamic during incremental exercise in poorly-controlled patients with uncomplicated type 1 diabetes : effect on aerobic fitness

L’objectif général de ce travail était d’évaluer l’effet du diabète de Type 1 et de l’hyperglycémie chronique (reflétée par un niveau élevé d’HbA1c), chez des patients indemnes de complications micro et macrovasculaires, sur la disponibilité en oxygène (O2) au niveau musculaire et cortical et ses répercussions sur l’aptitude physique aérobie. Dans un premier temps, nous nous sommes attardés à étudier l’effet du diabète et des niveaux élevés d’HbA1c sur les différentes étapes de la cascade d’oxygène (à savoir la diffusion alvéolo-capillaire, le transport artériel et la libération de l’O2 au niveau musculaire) ainsi que sur l’oxygénation musculaire estimée par la Spectroscopie dans le proche Infra-Rouge (NIRS) durant un exercice incrémental et voir les répercussions possibles sur la consommation maximale d’oxygène (〖V ̇O〗_2max). Nous avons montré que les patients DT1 présentent une capacité de diffusion alvéolo-capillaire ainsi qu’une capacité de transport artériel d’O2 comparable aux sujets sains. En revanche, les patients ayant un niveau élevé d’HbA1c présentent une altération de 〖V ̇O〗_2max ainsi qu’une réduction du volume sanguin musculaire (reflétée par une baisse de l’hémoglobine totale) et une nette baisse de la déoxyhémoglobine (HHb) au niveau du muscle actif aux intensités proches de l’exercice maximal. Ce dernier résultat pourrait s’expliquer par l’affinité plus importante de HbA1c pour l’O2 et/ou une altération de la redistribution de débit sanguin entre les vaisseaux nutritifs et non nutritifs. L’altération du volume sanguin au niveau musculaire chez les patients présentant un mauvais contrôle glycémique peut prévenir les cliniciens du dysfonctionnement de la microcirculation survenant avant même qu’une microangiopathie se manifeste à l’état clinique (Étude 1). Dans un second temps, nous nous sommes intéressés à la fonction cérébrale. Notre objectif étant d’évaluer l’hémodynamique cérébrale durant un exercice incrémental maximal. Nous avons trouvé une altération de l’hémodynamique cérébrale (baisse de l’hémoglobine totale) aux intensités proches de l’exercice maximal chez les patients DT1 qui présentent un mauvais contrôle glycémique (Étude 2). Ces deux travaux nous montrent bien que les sujets diabétiques de type 1 indemnes des complications micro et/ou marcovasculaires présentent une faible aptitude physique aérobie qui peut s’expliquer à la fois par une altération de l’oxygénation musculaire et cérébrale. Ces études mettent également en évidence l’intérêt d’associer la NIRS avec un exercice maximal. Ce dernier place les tissus en situation de besoin maximal en O2 ce qui permet de mettre en exergue des altérations fonctionnelles de la microcirculation avant même l’apparition de complications microvasculaires détectables par les tests cliniques habituels.This study sought to investigate whether type 1 diabetes and high levels of glycated hemoglobin (HbA1c) influence oxygen supply including alveolar capillary diffusion, oxygen delivery and release, to active muscle and prefrontal cortex during maximal exercise. We first studied the effect of high level of HbA1c on oxyhemoglobin dissociation at the active muscle measured by Near Infra-Red Spectroscopy (NIRS) during maximal exercise. We found that alveolar capillary diffusion and arterial oxygen content was comparable between patients with type 1 diabetes and healthy subjects. However, patients with inadequate glycemic control but without any clinically detectable vascular complications displayed an impaired aerobic capacity as well as a reduction in blood volume and a dramatic impairment in deoxyhemoglobin (HHb) increase in active skeletal muscle during intense exercise. The latter supports the hypotheses of an increase in O2 affinity induced by hemoglobin glycation and/or of a disturbed balance between nutritive and nonnutritive muscle blood flow. Furthermore, reduced exercise muscle blood volume in poorly controlled patients may warn clinicians of microvascular dysfunction occurring even before overt microangiopathy (Study 1). Secondly, we aimed at investigating prefrontal cortex hemodynamic during an incremental maximal exercise in patients with uncomplicated type 1 diabetes, taking into account chronic glycemic control. We observed that levels and changes in regional cerebral blood volume – as reflected by change in total hemoglobin – were lower at high intensities of exercise in patients with inadequate glycemic control (Study 2).In summary, the physiological stimulus of maximal exercise coupled with NIRS measurement highlighted subclinical disorders of both cerebral hemodynamic and muscle oxygenation in poorly-controlled patients with type 1 diabetes albeit free from any clinical microangiopathy

Acute cocoa flavanol improves cerebral oxygenation without enhancing executive function at rest or after exercise

Acute exercise-induced improvements in cognitive function are accompanied by increased (cerebral) blood flow and increased brain-derived neurotrophic factor (BDNF) levels. Acute cocoa flavanol (CF) intake may improve cognitive function, cerebral blood flow (in humans), and BNDF levels (in animals). This study investigated (i) the effect of CF intake in combination with exercise on cognitive function and (ii) cerebral hemodynamics and BDNF in response to CF intake and exercise. Twelve healthy men participated in this randomized, double-blind, crossover study. Participants performed a cognitive task (CT) at 100 min after acute 903-mg CF or placebo (PL) intake, followed by a 30-min time-trial. Immediately after this exercise, the same CT was performed. Prefrontal near-infrared spectroscopy was applied during CT and exercise to measure changes in oxygenated (Delta HbO(2)), deoxygenated (Delta HHb), and total haemoglobin (Delta Hb(tot)) and blood samples were drawn and analyzed for BDNF. Reaction time was faster postexercise, but was not influenced by CF. Delta HbO(2) during the resting CT was increased by CF, compared with PL. Delta HbO(2), Delta HHb, and Delta Hb(tot) increased in response to exercise without any effect of CF. During the postexercise cognitive task, there were no hemodynamic differences between CF or PL. Serum BDNF was increased by exercise, but was not influenced by CF. In conclusion, at rest, CF intake increased cerebral oxygenation, but not BDNF concentrations, and no impact on executive function was detected. This beneficial effect of CF on cerebral oxygenation at rest was overruled by the strong exercise-induced increases in cerebral perfusion and oxygenation

724-P: Timing of Basal Insulin Reduction to Prevent Hypoglycemia during Exercise in Adults and Adolescents with Type 1 Diabetes Using Insulin Pump Therapy: Preliminary Results

International audienceBackground We have shown that the reduction of basal insulin (-80%) 40-min before exercise is insufficient to reduce the time spent on hypoglycemia (Roy-Fleming et al., 2018. Diabetes and Metabolism). These results suggest that earlier basal insulin reductions need to be tested. We compared the efficacy of two timings to decrease basal insulin infusion rate to reduce exercise-induced hypoglycemia in patients with T1D using insulin pump therapy. Furthermore, we explored if decreased muscle vasoreactivity (secondary to decreased insulin levels) is associated with a reduced time spent in hypoglycemia. Methods: 13 adults and adolescents (10 adults; 5 adolescents; mean A1C: 8,2±1,0%) practiced 60-min exercise sessions (ergocyle) at 60% VO2peak, 240 minutes after a standardized lunch. In randomized order, we compared an 80% reduction of basal insulin applied 40-min (T-40) and 90-min (T-90) before exercise onset. Near-infrared spectroscopy (NIRS) was used to investigate muscle hemodynamic at vastus lateralis. Venous blood samples for glycemia measurement were drawn every 10 min during exercise. Results: T-90 strategy could reduce hypoglycemia risk during exercise: glycemic drop during exercise tend to be more important during T-40 vs. T-90 strategy (-41.44 ± 57.65 mg/dl vs. -14.05 ± 34.23 mg/dl respectively; p=0.09). This trend is confirmed by the repeated measures ANOVA test, which shows a significant interaction effects (blood glucose level during exercise × strategy “T90 vs. T-40”) (p = 0.01). However, contrary to our hypothesis, the estimation of local muscle perfusion measured by NIRS shows comparable results between 2-strategies. Conclusion: Our preliminary results in 15 DT1 patients (planned 20) show that decreasing basal insulin infusion rate by 80% up to 90 minutes before exercise onset tend to reduce exercise-induced hypoglycemia. This drop does not seem to be related to a decrease in local muscle perfusion

Anticipated basal insulin reduction to prevent exercise-induced hypoglycemia in adults and adolescents living with type 1 diabetes.

International audienceObjective: We investigated the effect of two key timings for basal insulin rate reduction on exercise-induced glucose changes and explored the association between circulating insulin concentrations and muscle vasoreactivity.Research Design and Methods: Twenty adults and adolescents performed 60-min exercise sessions (ergocycle) at 60% VO2peak, 240 min after a standardized lunch. In a randomized order, we compared an 80% basal insulin reduction applied 40 min (T-40) or 90 min (T-90) before exercise onset. Near-infrared spectroscopy was used to investigate muscle hemodynamics at vastus lateralis. Glucose and insulin plasma concentrations were measured.Results: Reduction in plasma glucose (PG) level during exercise was attenuated during T-90 versus T-40 strategy (−0.89 ± 1.89 mmol/L vs. −2.17 ± 2.49 mmol/L, respectively; P = 0.09). Linear mixed model analysis showed that PG dropped by an additional 0.01 mM per minute in T-40 versus T-90 (time × strategy interaction, P < 0.05). The absolute number of hypoglycemic events was not different between the two strategies, but they occurred later with T-90. Free insulin tends to decrease more during the pre-exercise period in the T-90 strategy (P = 0.08). Although local muscle vasodilatation (ΔTHb) was comparable between the two strategies, we found that PG dropped more in cases of higher exercise-induced skeletal muscle vasodilatation (ΔTHb × time interaction P < 0.005, e: −0.0086 mM/min and additional mM of ΔTHb).Conclusion: T-90 timing reduced exercise-induced drop in PG and delayed the occurrence of hypoglycemic episodes compared with T-40 timing without a significant reduction in the number of events requiring treatment

Muscle Oxygen Supply Impairment during Exercise in Poorly Controlled Type 1 Diabetes

PURPOSE: Aerobic fitness, as reflected by maximal oxygen (O(2)) uptake (V˙O(2max)), is impaired in poorly controlled patients with type 1 diabetes. The mechanisms underlying this impairment remain to be explored. This study sought to investigate whether type 1 diabetes and high levels of glycated hemoglobin (HbA(1c)) influence O(2) supply including O(2) delivery and release to active muscles during maximal exercise. METHODS: Two groups of patients with uncomplicated type 1 diabetes (T1D-A, n = 11, with adequate glycemic control, HbA(1c) <7.0%; T1D-I, n = 12 with inadequate glycemic control, HbA(1c) >8%) were compared with healthy controls (CON-A, n = 11; CON-I, n = 12, respectively) matched for physical activity and body composition. Subjects performed exhaustive incremental exercise to determine V˙O(2max). Throughout the exercise, near-infrared spectroscopy allowed investigation of changes in oxyhemoglobin, deoxyhemoglobin, and total hemoglobin in the vastus lateralis. Venous and arterialized capillary blood was sampled during exercise to assess arterial O(2) transport and factors able to shift the oxyhemoglobin dissociation curve. RESULTS: Arterial O(2) content was comparable between groups. However, changes in total hemoglobin (i.e., muscle blood volume) was significantly lower in T1D-I compared with that in CON-I. T1D-I also had impaired changes in deoxyhemoglobin levels and increase during high-intensity exercise despite normal erythrocyte 2,3-diphosphoglycerate levels. Finally, V˙O(2max) was lower in T1D-I compared with that in CON-I. No differences were observed between T1D-A and CON-A. CONCLUSIONS: Poorly controlled patients displayed lower V˙O(2max) and blunted muscle deoxyhemoglobin increase. The latter supports the hypotheses of increase in O(2) affinity induced by hemoglobin glycation and/or of a disturbed balance between nutritive and nonnutritive muscle blood flow. Furthermore, reduced exercise muscle blood volume in poorly controlled patients may warn clinicians of microvascular dysfunction occurring even before overt microangiopathy