Introduction:
Erythrocytes are unique cells as they lose all organelles upon maturity. They leave only a few metabolic pathways for energy production, reducing energy expenditure for the major functions they have to perform. This makes red blood cells highly sensitive to any disturbance. Impaired glucose metabolism in diabetic patients affects the morphological structure and physiological functions of red blood cells, causing microcirculatory insufficiency, and hypoxia (absence of oxygen in the tissues), promoting the development of diabetic complications and reducing the quality of life. This article explains this effect in detail.
What Are Erythrocytes?
Red blood cells are the most abundant type of cells in the blood. Their flexibility allows them to pass freely through capillaries, transport oxygen to tissues and release carbon dioxide to the lungs. Hemoglobin (Hb), the major oxygen-carrying protein, is most abundant in red blood cells. Erythrocyte membranes play an essential role in maintaining the cell’s morphological and functional stability. Red blood cells can transport oxygen through deformation, aggregation, and adhesion.
The atypical biconcave shape and a small amount of red blood cells provide:
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A large surface area-to-volume ratio.
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Allow oxygen and carbon dioxide to permeate inside and outside the cells quickly.
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Give them strong deformability.
In addition to transporting oxygen and carbon dioxide, red blood cells also have immune functions. Improving phagocytosis (cell engulfs a large particle), fighting off infections, increasing immune adhesion, antigen recognition, and trafficking, and clearing circulating immune complexes. Red blood cells are produced in the red bone marrow and released into the bloodstream after about seven days of maturation. Red blood cell production in bone marrow occurs at a staggering rate of over two million cells per second and is controlled by erythropoietin (EPO). These cells have an average lifespan of 100 to 120 days, and senescent red blood cells are degraded primarily in the reticuloendothelial system of the spleen and liver. The destruction and formation of human red blood cells help maintain dynamic balance and a stable red blood cell count.
What Is Diabetes?
Diabetes is a metabolic disorder characterized by hyperglycemia (high blood glucose) and defects in insulin secretion and/or action. Genetics, obesity, lack of exercise, poor diet, stress, urbanization, impaired glucose tolerance, and high blood pressure can increase the risk of diabetes. Chronic hyperglycemia in diabetic patients is associated with long-term damage and dysfunction of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels. This ultimately leads to various diabetic complications. These complications increase the risk of morbidity and mortality and reduce the patient's quality of life.
What Is the Relationship Between Diabetes and Erythrocytes?
In nondiabetic patients, erythrocytes are biconcave disc-shaped, with very high membrane integrity and cytoskeletal stability. This causes the erythrocyte membrane to deform significantly, allowing it to withstand the shear stresses generated as the cells pass through vessels of different diameters and turbulences of blood flow within the circulatory system.
As an important part of blood circulation, red blood cells are sensitive indicators of the body's health. Some erythrocyte parameter indices such as Hb concentration, hematocrit, and erythrocyte sedimentation rate (ESR) can be measured directly from blood, while some parameters such as mean cell volume (MCV), mean cellular Hb, mean cellular Hb concentration is a calculated index that can only be measured from a few measurements. These parameters reflect the erythrocyte condition from different perspectives and mainly assess the morphology, structure, function, and production of erythrocytes and can be used to further diagnose some diseases. With prolonged hyperglycemia, red blood cell morphology, metabolism, and function inevitably undergo a series of changes that further affect blood rheology and microcirculation.
The following properties of erythrocytes get affected due to raised blood sugar levels:
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Deformability - It is an intrinsic property of red blood cells that affects apparent blood viscosity. The deformability of red blood cells is due to their particular dynamic cell membrane geometry, which oxygenates tissues and organs via microcirculation and ensures effective blood flow. These factors increase the incidence of diabetic complications. Therefore, improving red blood cell deformability helps prevent diabetic complications.
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Agglutination - It describes the ability of red blood cells to stick together. It has been shown that the total protein content of red blood cell membranes (particularly glycoproteins) is decreased in diabetic patients. At the same time, sialidase activity is increased, and sialic acid on the red blood cell surface is decreased. As a result, the negative charge on the cell's surface is reduced, and red blood cell aggregation is increased. The aggregation state of erythrocytes in the plasma and serum could be used as a risk factor for diabetic foot.
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Fluidity - Red blood cell membrane fluidity refers to the relative lateral fluidity of proteins and lipids in the membrane structure. Many important biological membrane functions, such as cell metabolism and signal transduction, are closely related to membrane fluidity, which is essential for maintaining normal cell activity. Therefore, the increased aggregation, reduced deformability, and fluidity of erythrocytes caused by hyperglycemia can lead to increased blood viscosity and blood coagulation, leading to microcirculatory disturbances, an important factor in diabetic macrovascular and microvascular complications.
What Is the Relationship Between Erythrocytes and Oxidative Stress?
Oxidative stress is caused by an imbalance between the production and accumulation of reactive oxygen species (ROS) in cells and tissues and the ability of biological systems to detoxify these reaction products. The deformability of oxidative stress-damaged erythrocytes is greatly reduced, making it difficult for erythrocytes to cross microvessels, and it is closely associated with microvascular complications of diabetes. Therefore, enhancing antioxidant capacity and improving red blood cell structure and function may be a potentially effective way to prevent and treat complications of diabetes.
Conclusion:
Given the crucial role of erythrocytes in the pathological progression of diabetic complications, the corresponding levels of erythrocytes are correlated with the development and progression of these complications. There have been breakthroughs in the field of diabetes research. However, prevention and treatment of complications remain an important health issue. As one of the cells that can early and continuously sense changes in blood glucose levels, red blood cell-related indicators provide more clinical information and can be used to monitor the progression of diabetes and its complications.
