The study aimed to assess whether a short-term, high-intensity cold acclimation protocol would modulate finger vasomotor [i.e., finger temperature (TF), cold induced vasodilation (CIVD)] responses and regional thermo-perception to localized cooling. Six men performed a hand cold provocation (consisting of a 30-min immersion in 8°C water), while being whole-body immersed, once, in 21°C water (i.e., cold trial; HYPO), and, the following day, in 35.5°C water (i.e., normothermic trial; NORM). The local cold provocations were repeated, in the same order, after 10 days. In the intervening period, the subjects undertook a whole-body cold acclimation pro-tocol, consisting of daily whole-body 14°C-water immersions for 5 consecutive days, for a maximum of 2 h, while the skin temperature of the right hand was maintained at 35.6 (0.1)°C. Thermal (rectal temperature, skin temperature, finger temperature) cardiorespiratory (mean arterial pressure (MAP), heart rate and oxygen uptake), and perceptual responses (thermal sensation and comfort, pain, affective valence) were monitored throughout the trials. The acclimation protocol resulted in hypothermic adaptation (i.e., habituation), which was characterized by a modest reduction in shivering and an attenuation of whole-body thermal discomfort. The main finding of the study was that, regardless of subjects’ thermal status, the 5-day whole-body cold acclimation protocol did not alter TF (P > 0.1) and CIVD responses (P > 0.2) during local cold stress. Yet, after the acclimation, the cold-induced increase in MAP was reduced and tended to be reduced during the HYPO (P = 0.05) and NORM (P = 0.14) local cold provocation trials, respectively. Furthermore, the perceived thermal discomfort and pain in the immersed hand appeared to be alleviated in all post-acclimation trials.

Introduction : L’objectif de cette thèse était d'étudier les intégrateurs de risque cardiovasculaire chez des sujets qui représentent le continuum glycémique de la normo-glycémie jusqu'à la découverte du diabète, avant et après un petit déjeuner standardisé. Les paramètres que nous étudions étaient les suivants : l’endothélium, la rigidité artérielle et le système nerveux végétatif ou autonome (SNA). Méthodes : Dans un premier temps, nous avons mené une étude métabolique en utilisant des holters glycémiques. Ensuite nous avons étudié des sujets normo-glycémiques (NUTRIVASC: NCT01579409) intolérants au glucose (ACCES: NCT01521312) et diabétiques de type 2 avant et après un traitement par insuline (INSUVASC: 01022658). Nous avons étudié aussi le rôle des facteurs dit non classiques avec deux études sur l’association de la rigidité artérielle à la fibrose hépatique et la neuropathie diabétique. Conclusions : Nos résultats ont montré que la variabilité glycémique est plus forte en présence d’une dysglycémie et augmente avec l'HbA1c. Nous avons retrouvé une bonne corrélation entre la cinétique de la charge orale en glucose et celle d’un petit déjeuner standardisé. Chez les personnes âgées saines, l'augmentation du débit cardiaque après l'ingestion d'un repas dépend de l'augmentation de la FC sans que cet effet passe par l'inhibition vagale. Quatre semaines de traitement par insuline améliorait la fonction endothéliale microvasculaire à jeun. Parmi les patients diabétiques normotendus, ceux avec une neuropathie périphérique étaient deux fois plus susceptibles d'avoir une valeur de VOP > 90ème percentile des valeurs de référence que ceux sans neuropathie.La fibrose hépatique était corrélée à la rigidité artérielle indépendamment de l’âge et de la PA chez des sujets normotendus. Notre travail montre l’intérêt des explorations de la phase post-prandiale et l’étude des plusieurs cibles cardiovasculaires pour comprendre les différences de la PA et de la FC. / Introduction : The primary objective of this thesis was to study, at fasting and during the postprandial period, cardiovascular risk integrators in subjects representing the continuum from normoglycemia to insulin treated type 2 diabetes. We studied the following parameters : endothelial function, arterial stiffness and autonomic nervous system. Methods We have (i) conducted a metabolic study in obese subjects with continuous glucose monitoring systems ; (ii) studied subjects with normal glycemia (NUTRIVASC: NCT01579409), impaired glucose tolerance (ACCESS : NCT01521312) and (iii) type 2 diabetes before and after insulin treatment (INSUVASC: 01022658) ; and finally (iv) we studied the association of arterial stiffness with hepatic fibrosis and with diabetic neuropathy. Results(i) Glucose variability was higher in the presence of dysglycemia and increased with HbA1c. The kinetics of oral glucose tolerance test compared to a standardized breakfast were well correlated. (ii) In elderly patients without cardiovascular risk factors, the post-prandial increase in cardiac output depended on the increase in heart rate which was not driven by cardiac vagal inhibition ; The French National Nutrition Program recommendations had favorable effects on heart rate and myocardial viability. (iii) A 4-week treatment with insulin in addition to metformin improved microvascular endothelial function at fasting. (iv) In normotensive patients with diabetes, those with peripheral neuropathy have a two-fold higher risk for increased arterial stiffness than those without neuropathy. Finally, liver fibrosis correlates with arterial stiffness independently of age and blood pressure in normotensive subjects. Conclusions : Our work underlines the importance of exploring cardiovascular integrators during post prandial period in healthy subjects and in diabetic patients, according to their diet and their hypoglycemic and anti-hypertensive treatments.