Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxyhemoglobin dissociation curves (ODC) from zero to full saturation were developed from tests performed on whole blood from various groups of diabetic and nondiabetic healthy subjects. P50 at in-vivo pH was slightly but significantly lower than normal in ambulatory nonacidotic, uncomplicated juvenile diabetics (26.0 vs. 27.3 mm. Hg, P less than 0.001), despite increased red cell 2,3-diphosphoglycerate (2,3-DPG) concentrations in diabetic erythrocytes (15.0 vs. 13.7 mumole/gm. Hb, P less than 0.001). This combination of changes is in keeping with the presence of increased proportions of hemoglobin AIc in insulin-treated diabetics. The position of the ODC was positively correlated with the 2,3-DPG concentration (P less than 0.01), which varied in response to fluctuations in plasma concentration of inorganic phosphate (Pi) (P less than 0.001). Optimal metabolic control may lead to a normalization of the ODC in association with increased concentrations of red cell 2,3-DPG and P. When the diabetes was uncontrolled, the ODC was usually unchanged during the acidotic phase because the lowered pH balanced the effect of diminished 2,3-DPG concentration on the ODC. After correction of acidosis, the disproportion between erythrocyte 2,3-DPG and pH became quite prominent, accompanied by a corresponding fall in P50 (21.0 vs. 26.1 mm. Hg, P less than 0.001). Following ketoacidosis, with a persistently lowered Pi, it may take up to one week for 2,3-DPG to return to an approximately normal level, and the P50 will be impaired for the same period. A diphosphonate (EHDP) known to enhance tubular phosphate reabsorption in man was given to nonacidotic insulin-treated diabetic and healthy volunteers for 28 days. It caused a significant increase in mean Pi and P50 in both healthy and diabetic subjects (r = 0.58, P less than 0.01). When a dietary supplement of dibasic calcium phosphate was given to diabetic subjects for 28 days, a significant increase in P50 also occurred (25.2 vs. 27.2 mm. Hg, P less than 0.001). It is recommended that the diabetes diet be supplemented by dibasic calcium phosphate to prevent the inhibitory effect of a low concentration of Pi on red cell oxygen delivery.
Diabetes 1976
PMID:Oxygen transport impairment in diabetes. 0 22

The oxygen dissociation curve shifted less to the right in venous blood draining from muscle in eight insulin-deficient diabetics working at a constant submaximal workload than in seven normal controls (28.7 mm. Hg vs. 30.8 mm Hg; P less than 0.05). This diminution of the in-vivo Bohr effect at the muscle tissue level during exercise in diabetics was due to a significantly smaller decrease of venous blood pH (down to 7.33 vs. 7.27 in normals; P less than 0.05), probably a consequence of an latered muscle metabolism in insulin deficiency. Although no glucose was taken up, even during exercise, and less lactate was produced by insulin-deficient muscle (P less than 0.05), the differences in venous blood pH appeared to be brought about mainly by a different CO2 production of the exercising muscle in the two groups. The response of Krebs cycle activity to exercise in insulin-deficient muscle might have been inadequate, as suggested by the increased 3-hydroxybutyrate/acetoacetate ratio in the venous blood observed in the normal controls but not in the diabetics. Furthermore, proportionally less of the arterial ketone body concentration was utilized by the working muscle in the insulin-deficient diabetics. Changes in erythrocyte 2,3-diphosphoglycerate did not contribute to the differences in the in-vivo Bohr effect.
Diabetes 1976
PMID:Muscle metabolism during rest and exercise: influence on the oxygen transport system of blood in normal and diabetic subjects. 0 24

The relation between serum and red blood cell (RBC) inorganic phosphate levels, RBC 2,3-diphosphoglycerate (2,3-DPG) levels, RBC nucleotide phosphate (Pn), and RBC total phosphate (Pt) levels were studied during the early phases of treatment and recovery from diabetic ketoacidosis (DKA). A steady drop in serum inorganic phosphate was found during the first 24 hours of insulin treatment and was most profound at 24 hours. No statistically significant changes (P less than 0.05) were found in red cell inorganic phosphate or nucleotide phosphate levels during the 24-hour study period. The levels of total red cell phosphate were lower in this group of patients than in nonacidotic diabetic subjects and decreased slightly after 24 hours of treatment. The red cell 2,3-DPG levels were low at the initiation of therapy and remained low during the 24-hour study period. Glucose, bicarbonate, lactate, and ketone levels fell in linear patterns with treatment. In view of the current evidence for the effects of low 2,3-DPG on oxygen delivery and the relation of low serum phosphate levels to RBC glycolysis and 2,3-DPG formation, this study reemphasizes the need for phosphate replacement during the early phases of treatment of DKA.
Diabetes 1977 May
PMID:2,3-diphosphoglycerate, nucleotide phosophate, and organic and inorganic phosphate levels during the early phases of diabetic ketoacidosis. 1 18

The diagnosis of lactate acidosis is complicated by the fact that lactate determination is not a routine method in clinical chemistry. In fact, lactate analysis is performed only in special laboratories. Even in greater clinics this method is not routinely performed in differential diagnosis of acidotic states. Various diseases are accompanied by a lactate emia or even by lactate acidosis. Anaerobic synthesis of lactate is an emergency reaction to supply minimum energy to tissues with insufficient oxygen supply. The main diseases complicated by increased blood lactate concentrations are shock, circulatory collapse, cardiac failure and peripheral circularoty disturbance. Additionally diabetes mellitus, septical infections, and-the most prominent situation-biguanide intoxications are complicated by an increase in blood lactate concentration.
 ...
PMID:[Clinical picture of lactate acidosis. 4: Clinical significance of lactate acidosis]. 2 Mar 98

Oxyhemoglobin dissociation curves (ODC) were performed on blood from newly diagnosed, nonketotic diabetics prior to and following initial insulin treatment and from ambulatory juvenile diabetics before and after their usual morning insulin. In 10 newly discovered diabetics the average P50 at in vivo pH was normal prior to insulin (26.2 mm Hg), decreased to 24.5 mm Hg (p less than 0.005) on the day following the initial insulin administration, and was within normal limits (26.9 mm Hg) when the diabetes was finally well controlled and red cell 2,3-diphosphoglycerate (2,3-DPG) had risen to elevated levels. Oxygen affinity of hemoglobin was closely correlated with the content of red cell 2,3-DPG (r = 0.61, p less than 0.001) but was unrelated to the level of hemoglobin Alc. In 40 juvenile patients the average P50 was also normal prior to insulin administration but was significantly lower 3-4 hr after they had received their usual insulin dose (p less than 0.001). The study indicates that insulin administration to diabetics with high blood glucose levels may lead to transient decreases in red cell 2,3-DPG and in oxygen-releasing capacity of the red blood cells.
 ...
PMID:An adverse effect of insulin on the oxygen-release capacity of red blood cells in nonacidotic diabetics. 2 96

Studies are summarized to indicate that diabetes is associated with a fluctuating disturbance in the oxygen release capacity of the erythrocytes. This disorder, present from the onset of the disease, is a consequence of excess hemoglobin AIc, and absolute or relative hypophosphatemia and acidosis that interfere with formation of the red cell metabolite 2,3-diphosphoglycerate. As a result frequent increases in hemoglobin--oxygen affinity are produced. Available evidence suggests that transient decreases in red cell oxygen delivery lead to dilatation of the venous part of the microcirculation associated with increased transcapillary plasma permeation. Combined with microrheologic alterations (increased red cell aggregation, increased blood viscosity, and decreased red cell deformability) these functional changes may over the years participate in the pathogenesis of the microvascular disease in diabetes.
 ...
PMID:Changes in red cell oxygen release capacity in diabetes mellitus. 3 92

Studies of the microcirculation in diabetes in the last fifteen years have concentrated heavily on anatomic and biochemical abnormalities of the capillary basement membrane. Greater insights into basement membrane changes have eclipsed the previous picture of widespread progressive deterioration of the entire microcirculation. The history, variety of organ involvement, pattern of circulatory decline, and associated anatomic, physiologic, and biochemical findings are re-examined so that recently described potential mechanisms for the development of diabetic microangiopathy may be understood in a broader perspective. The possible contributions of seven categories of diabetic changes to damage of the microcirculation are outlined. The categories are: (1) altered basement membrane, (2) altered cellular function, (3) cell metabolic changes, (4) altered blood flow properties, (5) distrubed hemostasis, (6) altered oxygen transport, and (7) altered hormone production. The variety of clinical manifestations in long-standing diabetes related to microangiopathy appears to be due to a combination of a widely variable over-all rate of progression and a differing ability of body tissues and organs to accommodate to the sequential circulatory changes. The slow rate of deterioration in most diabetics suggests that several abnormalities must interact to produce the observed progression. A clear understanding of the interactions responsible for diabetic microangiopathy is becoming more important as new options in the management of diabetes become available.
Diabetes 1975 Oct
PMID:Deterioration of the microcirculation in diabetes. 17 Jan 55

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.
 ...
PMID:The problem of tissue oxygenation in diabetes mellitus. I. Its relation to the early functional changes in the microcirculation of diabetic subjects. 23 27

In order to study the determining factors for oxygen transport the oxyhaemoglobin dissociation curve (ODC), red cell 2,3-diphosphoglycerate (2,3-DPG), and plasma inorganic phosphate were estimated in insulin-requiring juvenile and adult diabetics in various conditions of metabolic control. 2,3-DPG has been shown to vary much more in diabetics than in normals, depending upon the state of metabolic control. These fluctuations of 2,3-DPG are mediated by variations in plasma inorganic phosphate as indicated by a close correlation. While 2,3-DPG was markedly decreased in diabetic ketoacidosis, it tended to be increased in ambulatory, non-acidotic patients. Since in the non-acidotic patients the oxygen-carrying capacity, i.e. the haemoglobin concentration was simultaneously elevated, these findings suggest the presence of relative tissue hypoxia in diabetes. Both in non-acidotic and in ketoacidotic patients there was a strong correlation between the amount of 2,3-DPG and the P50 at actual pH as an experssion of the oxygen affinity of haemoglobin. In order to guarantee an optimal erythrocyte oxygen release in diabetics the content of red cell 2,3-DPG and plasma inorganic phosphate should be higher than normal.
 ...
PMID:The problem of tissue oxygenation in diabetes mellitus. 23 28

Diabetes is associated with a fluctuating impairment in oxygen transport of the erythrocytes. This impairment is correlated with hyperglycemia by the formation of glycosylated hemoglobin (HbAIC) and with inhibitory factors of glycolysis i.e. hypophosphatemia and acidosis which lower the concentration of red cell 2,3-diphosphoglycerate. Diabetic angiopathy may be the ultimate result of innumerable microvascular responses to discrete hypoxic injuries associated with increased plasma permeation through the vessel walls. It is shown that two additional risk factors for atherosclerosis--smoking and hypertriglyceridemia may also lead to arterial wall hypoxia by changing the position of the oxyhemoglobin dissociation curve.
 ...
PMID:Diabetic vascular disease. The importance of insulin deficiency, hyperglycemia and hypophosphatemia on red cell oxygen unloading. 27 65


1 2 3 4 5 6 7 8 9 10 Next >>