In silico modeling of patient-specific blood rheology in type 2 diabetes mellitus.

Increased blood viscosity in type 2 diabetes mellitus (T2DM) is a risk factor for the development of insulin resistance and diabetes-related vascular complications; however, individuals with T2DM exhibit heterogeneous hemorheological properties, including cell deformation and aggregation. Using a multiscale red blood cell (RBC) model with key parameters derived from patient-specific data, we present a computational study of the rheological properties of blood from individual patients with T2DM. Specifically, one key model parameter, which determines the shear stiffness of the RBC membrane (µ) is informed by the high-shear-rate blood viscosity of patients with T2DM. At the same time, the other, which contributes to the strength of the RBC aggregation interaction (D0), is derived from the low-shear-rate blood viscosity of patients with T2DM. The T2DM RBC suspensions are simulated at different shear rates, and the predicted blood viscosity is compared with clinical laboratory-measured data. The results show that the blood viscosity obtained from clinical laboratories and computational simulations are in agreement at both low and high shear rates. These quantitative simulation results demonstrate that the patient-specific model has truly learned the rheological behavior of T2DM blood by unifying the mechanical and aggregation factors of the RBCs, which provides an effective way to extract quantitative predictions of the rheological properties of the blood of individual patients with T2DM.

Blood Viscosity in Subjects With Type 2 Diabetes Mellitus: Roles of Hyperglycemia and Elevated Plasma Fibrinogen.

The viscosity of blood is an indicator in the understanding and treatment of disease. An elevated blood viscosity has been demonstrated in patients with Type 2 Diabetes Mellitus (T2DM), which might represent a risk factor for cardiovascular complications. However, the roles of glycated hemoglobin (HbA1c) and plasma fibrinogen levels on the elevated blood viscosity in subjects with T2DM at different chronic glycemic conditions are still not clear. Here, we evaluate the relationship between the blood viscosity and HbA1c as well as plasma fibrinogen levels in patients with T2DM. The experimental data show that the mean values of the T2DM blood viscosity are higher in groups with higher HbA1c levels, but the correlation between the T2DM blood viscosity and the HbA1c level is not obvious. Instead, when we investigate the influence of plasma fibrinogen level on the blood viscosity in T2DM subjects, we find that the T2DM blood viscosity is significantly and positively correlated with the plasma fibrinogen level. Further, to probe the combined effects of multiple factors (including the HbA1c and plasma fibrinogen levels) on the altered blood viscosity in T2DM, we regroup the experimental data based on the T2DM blood viscosity values at both the low and high shear rates, and our results suggest that the influence of the elevated HbA1c level on blood viscosity is quite limited, although it is an important indicator of glycemic control in T2DM patients. Instead, the elevated blood hematocrit, the enhanced red blood cell (RBC) aggregation induced by the increased plasma fibrinogen level, and the reduced RBC deformation play key roles in the determination of blood viscosity in T2DM. Together, these experimental results are helpful in identifying the key determinants for the altered T2DM blood viscosity, which can be used in future studies of the hemorheological disturbances of T2DM patients.