Abstract
Diabetes mellitus, a metabolic disease characterized by chronically elevated blood glucose levels, affects about 29 million Americans and more than 422 million adults all over the world. Particularly, type 2 diabetes mellitus (T2DM) accounts for 90–95% of the cases of vascular disease and its prevalence is increasing due to the rising obesity rates in modern societies. Although multiple factors associated with diabetes, such as reduced red blood cell (RBC) deformability, enhanced RBC aggregation and adhesion to the endothelium, as well as elevated blood viscosity are thought to contribute to the hemodynamic impairment and vascular occlusion, clinical or experimental studies cannot directly quantify the contributions of these factors to the abnormal hematology in T2DM. Recently, computational modeling has been employed to dissect the impacts of the aberrant biomechanics of diabetic RBCs and their adverse effects on microcirculation. In this review, we summarize the recent advances in the developments and applications of computational models in investigating the abnormal properties of diabetic blood from the cellular level to the vascular level. We expect that this review will motivate and steer the development of new models in this area and shift the attention of the community from conventional laboratory studies to combined experimental and computational investigations, aiming to provide new inspirations for the development of advanced tools to improve our understanding of the pathogenesis and pathology of T2DM.
Highlights
Diabetes mellitus, coined for chronically elevated blood glucose levels, is a metabolic disease affecting about 29 million Americans and more than 422 million adults all over the world [1]
The biomechanics of diabetic red blood cell (RBC) have been studied by performing cell stretching tests, mimicking optical tweezers (OT) experiments
For D-RBC3, the authors observe that the axial diameters are roughly the same as those obtained for D-RBC2
Summary
Diabetes mellitus, coined for chronically elevated blood glucose levels, is a metabolic disease affecting about 29 million Americans and more than 422 million adults all over the world [1]. While the fibrinogen molecule is considered to be the major plasma protein promoting RBC rouleaux formation [7], high levels of synthetic dextran can increase the formation of RBC aggregates [8,9,10,11] Along this line, several in-vitro studies have been performed to quantify the adhesive forces between diabetic RBCs [8,12,13,14,15,16,16,17,18,19,20,21] using various experimental techniques, such as microfluidics, optical tweezers (OT), and atomic force microscopy (AFM). We will review the recent advances in modeling diabetic blood from the singlecell level to the blood flow in microvessels, including the biomechanics of single RBCs (Section 2), enhanced adhesion of diabetic RBCs (Section 3), biorheology of diabetic blood, and platelet margination (Section 4) as well as platelet aggregation in diabetic blood (Section 5), respectively
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