Abstract
Early in the progression of diabetes, a paradoxical metabolic imbalance in inorganic phosphate (Pi) occurs that may lead to reduced high energy phosphate and tissue hypoxia. These changes take place in the cells and tissues in which the entry of glucose is not controlled by insulin, particularly in poorly regulated diabetes patients in whom long-term vascular complications are more likely. Various conditions are involved in this disturbance in Pi. First, the homeostatic function of the kidneys is suboptimal in diabetes, because elevated blood glucose concentrations depolarize the brush border membrane for Pi reabsorption and lead to lack of intracellular phosphate and hyperphosphaturia. Second, during hyperglycemic-hyperinsulinemic intervals, high amounts of glucose enter muscle and fat tissues, which are insulin sensitive. Intracellular glucose is metabolized by phosphorylation, which leads to a reduction in plasma Pi, and subsequent deleterious effects on glucose metabolism in insulin insensitive tissues. Hypophosphatemia is closely related to a decrease in adenosine triphosphate (ATP) in the aging process and in uremia. Any interruption of optimal ATP production might lead to cell injury and possible cell death, and evidence will be provided herein that such cell death does occur in diabetic retinopathy. Based on this information, the mechanism of capillary microaneurysms formation in diabetic retinopathy and the pathogenesis of diabetic retinopathy must be reevaluated.
Highlights
Diabetic retinopathy is a leading cause of visual impairment in adults
Any interruption of optimal adenosine triphosphate (ATP) production might lead to cell injury and possible cell death, and evidence will be provided that such cell death does occur in diabetic retinopathy
Detailed statistical calculations of the DCCT study have revealed that the duration of diabetes and HbA1c explained only 11% of the variation in retinopathy risk, suggesting that the remaining 89% of the risk variation is due to other factors [4]
Summary
Diabetic retinopathy is a leading cause of visual impairment in adults. In proliferative diabetic retinopathy, ischemiainduced pathologic growth of new blood vessels often causes catastrophic loss of vision. Detailed statistical calculations of the DCCT study have revealed that the duration of diabetes (glycemic exposure) and HbA1c explained only 11% of the variation in retinopathy risk, suggesting that the remaining 89% of the risk variation is due to other factors [4] These observations indicate that glucose or a factor closely related to glucose metabolism, such as intracellular phosphate, may be a causative factor. Insulin treatment has modified the disease to a unique chronic condition characterized by a cellular glucose metabolism that is seldom in a steady state In both insulin-dependent (Type 1) and noninsulin-dependent (Type 2) diabetics, abnormally high blood glucose is linked to nonphysiologic variations in plasma insulin content throughout a 24-hour period, sometimes too little, and at other times too much. Depletion of endothelium and pericytes may obliterate capillaries and result in a resemblance to basement membrane tubes free of these cells, leading to the so-called “acellular capillaries.” Other vascular abnormalities may be associated with these lesions, such as thickening of capillary basement membrane, blot hemorrhages, exudates, dilatation and varicosities of capillaries and venules, increased vascular endothelium growth factor (VEGF), and other growth factors that stimulate further vascular permeability and neovascularization
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
