This prospective, multicenter, cross-sectional, repeated-measures comparative study compared functional and biochemical response profiles to exercise between 2 groups of chronically ill patients (chronic renal failure dialysis patients and patients with metabolic syndrome) and a group of healthy subjects.
The hypothesis is that the addition of plasma metabolic intermediates associated with energy disorders linked to insulin resistance, will improve the sensitivity of the assessment of muscle oxidative metabolism abnormalities, as reported in exercise intolerant subjects.
In this way, the metabolomics approach during exercise would provide a biological and functional "signature" of insulin resistance of muscular origin, discriminating between insulin-resistant patients, healthy control subjects and dialysis patients, with an exercise metabolic profile approaching that observed in insulin-resistant patients. A better understanding of metabolic abnormalities could guide muscle rehabilitation.
Participants will be asked to perform an exercise test, with several blood samples taken at different exercise intensities.
Researchers will compare the metabolic profile of three groups: patients with chronic kidney disease, patients with metabolic syndrome and healthy subjects:
* V'O2-adjusted lactate at rest and during exercise * The combination of exercise energy metabolism intermediates reflecting insulin resistance among Krebs cycle cofactors/substrates, ß-oxidation cofactors/substrates, amino acids
Postmenopausal women aged 40 to 75 or men aged 40 to 75
No chronic disease or treatment
BMI <30 kg/m², or
Fasting blood glucose < 1.10 g/dL
Non-stabilized pathology incompatible with physical exercise
Ongoing exercise retraining program
Nutritional supplementation in the 4 weeks preceding the study (antioxidants, vitamins, etc.)
Treatment influencing mitochondrial function (metformin, statin, etc.)
Parallel
Exercise test
Diagnostic test"Metabolic" effort test on cycloergometer with gas measurement. Gas exchanges (V'O2 and V'CO2) will be measured cycle-by-cycle using a gas analyzer connected to a flow meter Measurements will be taken every 6 minutes, at rest and during exercise on a cycloergometer, in five 6-minute increments, corresponding to intensities of 0% (rest), 20%, 30%, 40%, 50 and 60% of the subject's estimated maximum power, for a total duration of around 45 minutes.
Blood sample
Diagnostic testA catheter will be placed in a forearm vein to take blood samples at rest and at the end of the 5-stage stress test. Sampling times synchronized with stress test measurements
Impedancemetry
Diagnostic testmeasurement of anthropometric data (weight, height, waist circumference). impedancemetry will enable body composition to be analyzed by placing surface electrodes on the body. The participant will lie on an examination table and must remain at rest for 5 minutes.
Compare V'O2-adjusted plasma lactate profile at rest and during exercise (metabolic stress test), between chronic renal failure patients, patients with metabolic syndrome and healthy subjects.
Measurements will be taken every 6 minutes, at rest and during exercise on a cycloergometer, corresponding to intensities of 0% (rest) 20%, 30%, 40%, 50 and 60% of the subject's estimated maximum power. The gas exchange measurement (V'O2 and V'CO2 (milliliter per minute mL/min)) will be carried out cycle-by-cycle using a gas analyzer connected to a flow meter. The intensity corresponding to the rate of maximum lipid oxidation will be defined as LIPOXMAX, and will be expressed in Watts (W), and as a % of theoretical VO2max. Carbohydrate (G) and lipid (L) oxidation rates will be calculated as follows: * G (mg/min) = 4.585 VCO2 - 3.2255 VO2 * L (mg/min) = 1.6946 VO2 - 1.7012 VCO2 Blood sampling at various levels on a peripheral venous catheter synchronized with stress test measurements. A comparison will be made on the basis of an analysis of variance by ANOVA one way after verification of the conditions of application or a rank test by analysis via Kruskal-Wallis.
Compare between the 3 groups their metabolic profile (Krebs cycle cofactors/substrates) adjusted to V'O2 at rest and during exercise.
"Metabolic" Exercice test on a cycloergometer with gas measurement and peripheral venous sampling at various intensities. HOMA-IR score (Homeostatic model assessment of insulin resistance) is calculated using simultaneous measurement of insulin and plasma glucose levels, a score above 2.4 is diagnostic of insulin resistance. A combination of exercise energy metabolism intermediates based on candidate metabolites with a significant correlation coefficient \>0.7 compared to LIPOXmax and/or HOMA-IR, from among the following Krebs cycle cofactors/substrates : lactate, pyruvate, malate, citrate, succinate, fumarate and alpha-cetoglutarate Correlations will be characterized by Pearson's correlation test (correlation considered significant for coefficients \>0.7). Logistic regression analysis will be used to characterize insulin resistance in the different groups on the basis of the data collected.
Compare between the 3 groups their metabolic profile (ß-oxidation cofactors/substrates) adjusted to V'O2 at rest and during exercise.
"Metabolic" Exercise test on a cycloergometer with gas measurement and peripheral venous sampling at various intensities. HOMA-IR score (Homeostatic model assessment of insulin resistance) is calculated using simultaneous measurement of insulin and plasma glucose levels, a score above 2.4 is diagnostic of insulin resistance. A combination of exercise energy metabolism intermediates based on candidate metabolites with a significant correlation coefficient \>0.7 compared to LIPOXmax and/or HOMA-IR, from among the following ß-oxidation cofactors/substrates : free fatty acids, acyl-carnitine profile, beta-hydroxybutyrate, acetoacetate Correlations will be characterized by Pearson's correlation test (correlation considered significant for coefficients \>0.7). Logistic regression analysis will be used to characterize insulin resistance in the different groups on the basis of the data collected.
Compare between the 3 groups their metabolic profile (amino acids) adjusted to V'O2 at rest and during exercise.
"Metabolic" Exercise test on a cycloergometer with gas measurement and peripheral venous sampling at various intensities. HOMA-IR score (Homeostatic model assessment of insulin resistance) is calculated using simultaneous measurement of insulin and plasma glucose levels, a score above 2.4 is diagnostic of insulin resistance. A combination of exercise energy metabolism intermediates based on candidate metabolites with a significant correlation coefficient \>0.7 compared to LIPOXmax and/or HOMA-IR, from among the following amino acids. Correlations will be characterized by Pearson's correlation test (correlation considered significant for coefficients \>0.7). Logistic regression analysis will be used to characterize insulin resistance in the different groups on the basis of the data collected.
Compare between the 3 groups their metabolic profile (acyl-carnitine profiles) adjusted to V'O2 at rest and during exercise.
"Metabolic" Exercise test on a cycloergometer with gas measurement and peripheral venous sampling at various intensities. HOMA-IR score (Homeostatic model assessment of insulin resistance) is calculated using simultaneous measurement of insulin and plasma glucose levels, a score above 2.4 is diagnostic of insulin resistance. A combination of exercise energy metabolism intermediates based on candidate metabolites with a significant correlation coefficient \>0.7 compared to LIPOXmax and/or HOMA-IR, from among the following acyl-carnitine profiles Correlations will be characterized by Pearson's correlation test (correlation considered significant for coefficients \>0.7). Logistic regression analysis will be used to characterize insulin resistance in the different groups on the basis of the data collected.
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