Training-induced improvement in lipid oxidation in type 2 diabetes mellitus is related to alterations in muscle mitochondrial activity. Effect of endurance training in type 2 diabetes.

AIM: We investigated whether or not, in type 2 diabetic (T2D) patients, an individualized training effect on whole-body lipid oxidation would be associated with changes in muscle oxidative capacity. METHODS: Eleven T2D patients participated in the study. Whole-body lipid oxidation during exercise was assessed by indirect calorimetry during graded exercise. Blood samples for measuring blood glucose and free fatty acids during exercise, and muscle oxidative capacity measured from skeletal muscle biopsy (mitochondrial respiration and citrate synthase activity), were investigated in the patients before and after a 10-week individualized training program targeted at LIPOXmax, corresponding to the power at which the highest rate of lipids is oxidized (lipid oxidation at LIPOXmax). RESULTS: Training induced both a shift to a higher-power intensity of LIPOXmax (+9.1+/-4.2W; P<0.05) and an improvement of lipid oxidation at LIPOXmax (+51.27+/-17.93 mg min(-1); P<0.05). The improvement in lipid oxidation was correlated with training-induced improvement in mitochondrial respiration (r=0.78; P<0.01) and citrate synthase activity (r=0.63; P<0.05). CONCLUSION: This study shows that a moderate training protocol targeted at the LIPOXmax in T2D patients improves their ability to oxidize lipids during exercise, and that this improvement is associated with enhanced muscle oxidative capacity.

Exercise calorimetry in sedentary patients: procedures based on short 3 min steps underestimate carbohydrate oxidation and overestimate lipid oxidation.

OBJECTIVES: Among exercise calorimetry tests designed for calculating the respective part of carbohydrates and lipids oxidized at exercise, some use 6 min steps and others use 3 min steps. Is this last method, which has been validated in healthy subjects, still accurate in very sedentary patients, who need more time to reach a steady state in respiratory gas exchanges? METHODS: We compared data obtained with calorimetry (RER and indicators of substrate oxidation) performed on the 2nd-3rd min and the 5th-6th min of each step of a protocol using four 6-min submaximal steps in 17 sedentary subjects (mean age: 51 years) including seven type 2 diabetics and six obese persons. RESULTS: Respiratory exchange ratio (RER) measured with the 3 min steps procedure are well correlated with the 6 min procedure in sedentary patients (r=0.928). However, a Bland-Altman analysis indicated an average underestimation of RER with 3 min steps (-0.0138). Moreover, we observed an average underestimation of carbohydrate oxidation rates of 70.1 mg/min with the 3 min steps procedure. On the contrary, as to lipid oxidation, we measured an average overestimation of 16.2 mg/min. Furthermore, carbohydrate and lipid oxidation rates measured with the 3 min steps procedure are well correlated with the 6 min steps procedure. Moreover, there was an average overestimation of the point at cross over with 3 min steps (+3.29 Watts). For lipox max point (power at which the increase in lipid oxidation induced by the increasing workload reaches a maximum), we observed an average underestimation with 3 min steps (-1.88 Watt). Although the differences between respectively mean values in cross over point and lipox max point between the two protocols are weak, a Bland-Altman analysis indicated more relevant discrepancies in many subjects between the two protocols. CONCLUSION: In very sedentary patients undergoing such tests for targeting exercise prescription, the 3-min procedure appears to be too short for performing an accurate calorimetry and we rather recommend the protocol using 6-min steps.

[Late diagnosis of a McArdle disease's case (type V glycogenosis)]. / Diagnostic tardif d'une maladie de McArdle (glycogénose de type V).

McArdle's disease is a metabolic myopathy characterized by a myophosphorylase deficiency resulting in an inability to degrade glycogen stores. We report the case of a 48 years old patient who complained since adolescence of rest and exercise myalgias and presented a chronic increased plasma creatine kinase activity. First, a maximal exercise test was performed. This test demonstrated a quasi lack of rise of respiratory exchange ratio and of blood lactate, possibly due to a glycogenolytic/glycolytic pathway deficiency. Second, a biopsy of vastus lateralis muscle was performed using Bergström needle. As expected, the analysis of mitochondrial function was normal. The in vitro screening test of the glycogenolysis/glycolysis pathway showed a lack of lactate production in presence of glycogen substrate. The study of muscular metabolism of glycogen revealed a glycogen accumulation and a decrease of active and total phosphorylase activities. These data allowed us to diagnose a type V glycogenosis, or McArdle's disease. The patient appeared heterozygous for the most frequent mutation (p.R50X).

Metabolic training: new paradigms of exercise training for metabolic diseases with exercise calorimetry targeting individuals.

For patients with metabolic diseases, as with other diseases, exercise training is a fully recognized therapy. Such training helps obese patients stabilize weight after slimming. For patients with type 2 diabetics, it is both a prevention and a glucose-lowering treatment and reduces health care costs. We propose a targeted training for individuals at the level of maximal lipid oxidation (LIPOXmax) with a protocol of exercise calorimetry (four 6-min workloads) based on Brooks and Mercier's crossover concept. Calorimetric interpretation of gas exchange at the fifth and sixth minutes of each stage shows a bell-shaped curve for lipid oxidation that peaks at LIPOXmax, a point that varies considerably among individuals. As well, glucose oxidation is a linear function of power (carbohydrate cost of the watt). Such a calculation predicts fairly actual lipid oxidation over 45 min at the same level. Other protocols, with 3-min workloads used in sports medicine, are not reliable for patients with metabolic diseases. For obese adults and teenagers, as well as those with type 2 diabetes, 2 months' training at the LIPOXmax (three sessions at 45 min per week) results in a net loss of fat mass, with preserved fat-free mass, and increased ability to oxidize lipids. At the end of this period, training can be "re-targeted" to be more effective and, possibly, associated with other strategies with stronger exercise intensities. Therefore, metabolic training is a viable option for patients with metabolic diseases, but the full concept is still evolving. However, the major challenge remains to transform inactive individuals into active ones.