Abstract
In this paper, we present the optical characterisations of diabetic red blood cells (RBCs) in a non-invasive manner employing three-dimensional (3-D) quantitative phase imaging. By measuring 3-D refractive index tomograms and 2-D time-series phase images, the morphological (volume, surface area and sphericity), biochemical (haemoglobin concentration and content) and mechanical (membrane fluctuation) parameters were quantitatively retrieved at the individual cell level. With simultaneous measurements of individual cell properties, systematic correlative analyses on retrieved RBC parameters were also performed. Our measurements show there exist no statistically significant alterations in morphological and biochemical parameters of diabetic RBCs, compared to those of healthy (non-diabetic) RBCs. In contrast, membrane deformability of diabetic RBCs is significantly lower than that of healthy, non-diabetic RBCs. Interestingly, non-diabetic RBCs exhibit strong correlations between the elevated glycated haemoglobin in RBC cytoplasm and decreased cell deformability, whereas diabetic RBCs do not show correlations. Our observations strongly support the idea that slow and irreversible glycation of haemoglobin and membrane proteins of RBCs by hyperglycaemia significantly compromises RBC deformability in diabetic patients.
Highlights
IntroductionConsequences of all diabetes types include chronically elevated blood glucose levels, i.e. hyperglycaemia, caused by a lack of insulin or loss of insulin-mediated metabolic functions, which eventually results in a wide range of complications ranging from microvascular diseases including retinopathy, neuropathy and nephropathy, and cardiovascular diseases, to severe depression and dementia
Diabetes mellitus is a life-threatening disease affecting many people
Because the refractive index (RI) value of the red blood cells (RBCs) cytoplasm is linearly proportional to the intracellular Hb concentration with a known proportionality coefficient, RI increment30, the RI value of RBC can be directly related to Hb concentration
Summary
Consequences of all diabetes types include chronically elevated blood glucose levels, i.e. hyperglycaemia, caused by a lack of insulin or loss of insulin-mediated metabolic functions, which eventually results in a wide range of complications ranging from microvascular diseases including retinopathy, neuropathy and nephropathy, and cardiovascular diseases, to severe depression and dementia. Characterisation of the deformability of red blood cells (RBCs) is crucial to understanding the pathophysiology of diabetes because it is strongly related to the disease’s complications. The main cytoplasmic alteration in diabetic RBCs caused by hyperglycaemia, the glycation of haemoglobin (Hb), has gained increasing attention because the relative amount of glycated Hb, mainly consisting of HbA1c to total Hb, reflects the mean plasma glucose concentration of the previous three months. Damage to RBC membranes resulting from chronic hyperglycaemia have been accessed by measuring end products of lipid-peroxidation. Instant effects of in vitro glucose treatments on RBC deformability have been addressed
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