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31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), Dusseldorf, GERMANY, OCT 13-17, 2018; International audience

International audience; Defects in insulin sensitivity are associated with metabolic inflexibility and obesity albeit some obese subjects have preserved insulin sensitivity. A decrease in lipid oxidation during exercise can be found in obesity and type 2 diabetes. This lipid oxidation capacity has been found to be associated in healthy or overweight subjects with insulin sensitivity and mitochondrial function. Thus, we aimed at delineate the interrelationships among the maximal ability to oxidize lipids at exercise (LIPOXmax) insulin sensitivity and mitochondrial function in middle-aged obese men with different levels of insulin sensitivity.After an overnight fast, twenty middle-aged male obese subjects performed: a maximal incremental exercise test allowing the determination of LIPOXmax, two days after a measurement of insulin sensitivity and two days after a muscle biopsy for mitochondrial respiration.According to the minimal model, we found 9 insulin-resistant and 11 insulin-sensitive middle-aged obese men. LIPOXmax (expressed as power intensity) and whole-body insulin sensitivity are significantly correlated in obese insulin-sensitive but not in insulin-resistant obese men. LIPOXmax and insulin sensitivity are correlated to mitochondrial pyruvate oxidation and mitochondrial density. Multivariate analysis indicates that insulin sensitivity is statistically better explained by the LIPOXmax which is in turn better explained by the mitochondrial function parameter Vmax/V0 pyruvate.Thus, insulin sensitivity, mitochondrial function and the ability of muscle to oxidize lipids during exercise are three closely correlated parameters in middle-aged male obese insulin-sensitive patients.

International audience

International audience

We previously reported in populations exhibiting all the spectrum of insulin sensitivity (SI) values correlations between SI and blood viscosity eta suggesting that high eta is an additional symptom of the insulin resistance syndrome. However, due to the elevation of insulinemia (I) which is usually associated with insulin resistance it remained to determine whether this relationship was explained by SI or I. We analyzed SI with the minimal model procedure in 108 nondiabetic subjects and analyzed correlations of SI with blood rheology (eta, RBC aggregation and rigidity). Across quartiles of SI (defined after log transformation since distribution of SI was not normal), hematocrit and red cell rigidity remained stable, while aggregability and plasma viscosity (etap) increased in the lowest quartile. SI was correlated to only two rheological parameters: etap (r= -0.280, p=0.005) and Myrenne index M1 (r= -0.219, p=0.044). Among SI, I, age and BMI multivariate analysis selected only BMI as a determinant of either whole blood viscosity (etawb: r= -0.301, p=0.004) and RBC disaggregation threshold (gammaD: r= -0.331, p=0.013), only I as determinant of M1 (r=0.254, p=0.03), and a combination of BMI (p=0.009) and SI (p=0.007) for etap. Although age and obesity are factors of hyperviscosity, the hemorheological disturbances found in insulin resistance are not fully statistically "explained" by those two factors. While hyperaggregability (measured with M1) is rather related to hyperinsulinism, etap is influenced by SI and should be further investigated as a simple marker for the follow up of insulin-resistant states.

We aimed at investigating relationship between plasma fibrinogen and insulin sensitivity, which are two major determinants of metabolic Syndrome X (insulin resistance syndrome). We designed a prospective study of 27 non-diabetic, non-hypertensive subjects, presenting a wide range of body mass index BMI (10 men, 17 women; mean age+/-SEM: 35.9+/-2.2 years; BMI ranging from 21.1-45.2 kg/m2). Insulin sensitivity was assessed with the minimal model procedure, over a 180 min intravenous glucose tolerance test with iterative sampling. Fibrinogen levels were determined by the method of Clauss. The insulin sensitivity index SI (i.e., the slope of the dose-response relationship between insulin increased above baseline and glucose disposal) ranged from 0.0009 to 16 x 10(-4) min(-1)/(microU/ml), with a mean value of 4.76+/-0.73 x 10(-4). Mean values of plasma fibrinogen were 3.33+/-0.13 g/l, ranging from 2.21 to 5.07 g/l. There were highly significant negative correlations between SI and the level of plasma fibrinogen (r = -0.61, p = 0.0007) and between the basal effect of insulin BIE and plasma fibrinogen (r = -0.521, p = 0.005). Basal insulin was positively correlated to fibrinogen (r = 0.386, p = 0.046). When we analysed the data using partial correlation analysis, the negative relation between SI and fibrinogen was maintained independently from BMI (r = -0.45, p0.05). These data establish a strong negative association between insulin sensitivity and fibrinogen, involved in the increased cardiovascular risk of metabolic Syndrome X.