Probably, the control subjects had high normal blood glucose levels or were prediabetic. This allows understanding of why in some studies, no difference was observed between patients with diabetes and control subjects ( 27, 28). The observation that the change in viscosity is already evident at blood glucose values >90 mg/dL seems very important. Clearly, this requires further study for a more exact definition. It cannot be excluded that a slight increase in blood glucose, secondary to other conditions of insulin resistance such as aging, inflammation, physical inactivity, etc., can cause increased BV, thereby creating a vicious circle. If increased viscosity somehow alters the supply of oxygen and nutrients to the tissues, then the observed changes may contribute to the development of peripheral insulin resistance (by reduced glucose utilization in the muscle) and, in the long term, diabetes. Furthermore, these findings are also in line with the results of a previous study, which showed that the BV in patients with prediabetes was comparable with that of diabetic subjects with complications ( 36) and significantly higher than that of healthy control subjects. This supports the hypothesis that the alterations are very early and present in any flow condition. The findings of our study are in line with the conclusions of the ARIC Study and further demonstrate that the BV of the subjects with prediabetes or high normal blood glucose is significantly higher compared with that of subjects with low normal blood glucose at all considered shear rates. In that study, the authors did not directly measure BV but used two validated formulas: one for the shear rate 208 s −1 and the other for the shear rate 0.5 s −1 ( 35). The importance of BV was recently highlighted after the observation that it increases the risk of developing diabetes in normoglycemic subjects participating in the Atherosclerosis Risk in Communities (ARIC) study ( 18). In light of this, it is evident that further studies are needed to clarify the relationship between diabetes and BV. Furthermore, factors such as cigarette smoking, hyperlipidemia, and hyperfibrinogenemia, which are very frequent in patients with diabetes, may alter BV. The deformability and the aggregation of erythrocytes are, in turn, driven by different characteristics of the erythrocytes and the plasma. BV at high shear rates (≥90 s −1, corresponding with in vivo systolic flow condition) is strongly influenced by erythrocyte deformability, while at lower shear rates (representing in vivo diastolic flow condition) red cell aggregation plays the most important role ( 34). In conditions of low flow velocities, the cellular component occupies the entire column of flowing blood, causing an increase in viscosity. Specifically, when the flow velocity is high, the cellular component of blood (red cells, white cells, and platelets) is concentrated at the center of the vessel, while the plasma flows in the periphery. First, it is useful to underline that the blood is a non-Newtonian fluid, in that its viscosity varies with the flow velocity. However, the relationship between blood glucose, diabetes, and viscosity may be much more complex. Overall, changes in viscosity in diabetic patients are accepted as common and as a result of the disease. Once retinopathy has developed, its progression may be favored by a reduction in BV and hemoglobin ( 33). Important increases in BV have been reported in diabetic retinopathy, and it has been hypothesized that these changes lead to a prolonged reduction in the supply of oxygen and nutrients to the capillaries, causing the development of angiopathy ( 31, 32). Some findings have suggested a role for the increase in BV as a pathogenetic factor for the development of microvascular complications ( 29, 30). Usually, however, these studies were performed in small groups of patients, often only at few shear rates, and sometimes did not demonstrate any difference between diabetic and control subjects ( 27, 28). Many studies thus far have investigated BV in patients with diabetes ( 26).
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