Eric Raynaud

Relationships between fibrinogen and insulin resistance.

A relationship between plasma fibrinogen levels and insulinemia, as well as the different parameters of the insulin resistance syndrome has been described. The aim of the present paper was to investigate whether plasma fibrinogen concentrations were linked to plasma insulin levels or to the degree of insulin resistance. For this purpose, 62 nondiabetic, nonhypertensive patients, 30 men and 32 women, with body mass indexes (BMIs) and ages ranging from 18.6 to 50.2 kg/m(2) and from 19 to 60 years, respectively, were studied. Insulin sensitivity was quantified by the minimal model procedure over a 180-min intravenous glucose tolerance test with iterative sampling. Plasma insulin was determined by radioimmunoassay without cross-reactivity to human proinsulin, and fibrinogen by the method of Clauss. Insulin sensitivity ranged from 0.009 to 23.2 min(-1)/(microU/ml)x10(-4), covering the whole range of insulin sensitivities. Fibrinogen ranged from 1.70 to 5.07 g/l. There was a significant negative correlation between fibrinogen and insulin sensitivity (r=-0.76,P<0.0001) and a positive correlation between fibrinogen and basal insulin (r=0.56,P<0.0001). After adjustment for BMI, body fat mass and waist-to-hip ratio, these two relationships remained significant. In addition, a multiple regression analysis was performed to assess the independent effect of the following related variables: fibrinogen, insulin sensitivity, insulinemia and BMI. Only insulin sensitivity appeared to account for the ability to predict fibrinogen values. Thus, we hypothesized it was likely that the state of insulin resistance rather than hyperinsulinemia per se was related to hyperfibrinogenemia. We proposed an interpretation of these data in connection with some factors like free fatty acids or tumor necrosis factor-alpha, which have been implicated in the pathogenesis of insulin resistance. Nevertheless, prospective and intervention studies are needed to assess whether there is a simple association or a causal relationship between insulin resistance and hyperfibrinogenemia.

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.

Substrate oxidation during exercise: type 2 diabetes is associated with a decrease in lipid oxidation and an earlier shift towards carbohydrate utilization

OBJECTIVES Exercise is a recommended treatment for type 2 diabetes but the actual pattern of metabolic adaptation to exercise in this disease is poorly known and not taken in account in the protocols used. Metabolic defects involved in the pathways of substrate oxidation were described in type 2 diabetes. We hypothesized that type 2 diabetes, regardless of age, gender, training status and weight, could influence by its own the balance of substrates at exercise. METHODS 30 sedentary type 2 diabetic subjects and 38 sedentary matched control subjects were recruited. We used exercise calorimetry to determine lipid and carbohydrate oxidation rates. We calculated two parameters quantifying the balance of substrates induced by increasing exercise intensity: the maximal lipid oxidation point (PLipoxMax) and the Crossover point (COP), intensity from which the part of carbohydrate utilization providing energy becomes predominant on lipid oxidation. RESULTS Lipid oxidation was lower in the diabetic group, independent of exercise intensity. PLipoxMax and COP were lower in the diabetic group [PLipoxMax=25.3+/-1.4% vs. 36.6+/-1.7% %Wmax (P<0.0001)] - COP =24.2+/-2.2% vs. 38.8+/-1.9% %Wmax (P<0.0001). CONCLUSIONS Type 2 diabetes is associated with a decrease in lipid oxidation at exercise and a shift towards a predominance of carbohydrate oxidation for exercise intensities lower than in control subjects. Taking into account these alterations could provide a basis for personalizing training intensity.

Adrenocorticotropic hormone (ACTH) responsiveness to standardized exercise as a marker of neuroendocrine maturation during puberty

Summary A cross-sectional study of 56 children undergoing a 15 min submaximal exercise-test shows that ACTH increases during exercise only in postpubertal children.