Hemorheological aspects of the metabolic syndrome: markers of insulin resistance, obesity or hyperinsulinemia?

The metabolic syndrome is a major health problem in western countries, due to the deleterious metabolic consequences of sedentarity and rich diet in the large part of the population who exhibits the so-called "thrifty phenotype". This syndrome, which is at high risk for diabetes and atherothrombosis is associated with hemorheologic abnormalities. Initially, insulin resistance was considered as the core of the syndrome. However, it becomes clear that the syndrome is a cluster in which the combined effects of obesity, insulin resistance, and hyperinsulinemia can be inconstantly associated. Thus, we investigated in 157 nondiabetic subjects (53 males and 104 females, age 35.6+/-1.1 yr, mean BMI 29.2+/-0.6 kg/m2) the respective importance of each of these factors. Subjects were divided in 6 groups according to BMI (cut-off point 25 kg/m2) and insulin sensitivity (SI) measured with the minimal model (lowest quartile SI<1.1 min(-1)/(microU/ml) x 10(-4), highest quartile SI>9.5, middle zone between 1.1 and 9.5). Results show that whole blood viscosity at high shear rate is higher in obese subjects (p<0.01). Plasma viscosity is also higher in obese subjects 1.41+/-0.02 vs 1.34+/-0.012 (p<0.01), and, in addition, in lean subjects, is lower when SI is in the upper quartile. RBC rigidity index "Tk" is higher in obese subjects. A worsening effect of insulin resistance (SI<1.1) on Tk is found only in obese subjects. The aggregability index "M1" is increased when SI<1.1 in both obese and nonobese subjects. No clear effect of either SI or obesity on hematocrit is observed. On the whole, obesity and insulin resistance both impair blood rheology by acting on red cell rigidity and plasma viscosity. Whole blood viscosity at high shear rate reflects rather obesity than insulin resistance. Myrenne "M1" aggregation is rather a marker of hyperinsulinemia. Thus, the hemorheologic picture of the metabolic syndrome is far to be only a reflect of insulin resistance alone.