title: The problem of tissue oxygenation in diabetes mellitus. I. Its relation to the early functional changes in the microcirculation of diabetic subjects.
abstract: The underlying cause leading to the reversible functional changes in the microcirculation of insulin-dependent diabetic subjects early during the disease prior to any clinical signs of retinopathy and nephropathy (functional microangiopathy) is discussed. It is suggested that the initial microvascular dilation observed in diabetics is due to an autoregulatory response to relative tissue hypoxia providing an increased tissue perfusion in order to improve tissue oxygen delivery. Supporting evidence for this suggestion is derived from the findings that diabetics simultaneously may show increased tissue oxygen consumption and decreased ability of the circulating blood to release oxygen to the tissues. The latter defect is likely to be caused by two interrelated factors: 1. an increased proportion of haemoglobin A1c with high oxygen affinity, and 2. difficulties of maintaining a sufficiently high concentration of plasma inorganic phosphate in order to provide an optimal 2,3-diphosphoglycerate (2,3-DPG) content in the erythrocytes. The basal oxygen demand of diabetics may fluctuate even within a few hours dependent upon the state of metabolic control and is increased at times of poor regulation. Hence, diabetics may suffer from innumerable cellular hypoxic injuries, which during the first years of the disease are counteracted in the microcirculation by an autoregulatory response. These microvascular reactions associated with increased plasma permeation may over the years be of major importance for the development of the degenerative microangiopathy in diabetes.
mesh_terms: D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism*; D004163:Diphosphoglyceric Acids / Q000097:blood; D004912:Erythrocytes / Q000378:metabolism; D006454:Hemoglobins / Q000032:analysis; D006706:Homeostasis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008833:Microcirculation; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption
chemical_list: D004163:Diphosphoglyceric Acids; D006454:Hemoglobins; D010100:Oxygen