Jørn Ditzel

The Oxygen Transport System of Red Blood Cells during Diabetic Ketoacidosis and Recovery

SummaryDaily evaluations of 8 newly detected ketoacidotic diabetics showed the Bohr-effect of haemoglobin to be decreased by 50% while erythrocyte 2,3-DPG was decreased below 10 μmoles/g Hb. 2,3-DPG correlated strongly with pH during acidosis and with plasma inorganic phosphate (Pi) subsequently to the first insulin administration. Oxygen affinity of haemoglobin, measured as P50 act pH, was unchanged in ketoacidosis compared to the time before discharge. After correction of acidosis, however, P50 act pH fell strikingly (p < 0.001) and remained decreased up to 7 days depending upon the resynthesis of 2,3-DPG in relation to Pi. The Hill-coefficient n reflecting the slope of the oxygen dissociation curve was diminished in ketoacidosis (p < 0.005), and decreased further after pH-normalization (p < 0.005). There was a close association of n with 2,3-DPG (p < 0.001) and additionally with Pi at 2,3-DPG-levels below 10 μmoles/ g Hb. Based on these findings a decreased erythrocyte oxygen release of one fifth during acidosis and more than one third after pH-correction can be hypothesised. In view of the intimate relation of Pi to the oxygen transport system it is suggested that treatment of ketoacidosis should include Pisubstitution.

Micro vascular permeability to albumin and glomerular filtration rate in diabetic and normal children

SummaryIn order to examine the permeability of microvessels in diabetic children, the glomerular filtration rate, urinary excretion rates of albumin and β2-microglobulin, intravascular mass of albumin, and transcapillary escape rate of albumin were studied in 26 diabetic children without clinical signs of microangiopathy (age: 7–14 years; duration of disease: 3–14 years). Similar measurements were made in 28 healthy school children (age: 8–14 years). Mean glomerular filtration rate in the diabetic children was higher than in the normal children (138 versus 109 ml/min per 1.73 m2, p<0.01). Urinary excretion rates of albumin and β2-microglobulin did not differ in diabetics. Mean intravascular albumin mass in the diabetic girls (1.64 g/kg body weight) was lower (p<0.01) than in the diabetic boys (1.89 g/kg body weight) and also lower (p<0.02) than in the normal girls (1.94 g/kg body weight). Mean transcapillary escape rate of albumin in the twenty diabetics with duration of diabetes less than 10 years (7.14%/h) was lower (p<0.01) than that in normal children (8.90%/h); the escape rate showed a positive correlation with duration of diabetes (r=0.47; p<0.02). Thus glomerular filtration rate in diabetic children is elevated to the same extent as in adult short-term juvenile diabetics while the permeability of the glomerular membrane to macromolecules is normal. Interpretation of the results on intravascular albumin mass and transcapillary escape rate of albumin requires further investigation.

Changes in red blood cell oxygen transport in diabetic pregnancy

Parameters of red cell oxygen transport were studied in 23 nonsmoking, insulin-dependent diabetic women and 20 nonsmoking healthy women late during pregnancy. In the pregnant diabetic women, arterial oxygen saturation (SAT) and arterial oxygen tension were significantly decreased. SAT correlated inversely with hemoglobin Alc (Hb Alc) (diabetic women: r = -0.43, p less than 0.05; total material: r = 0.66, p less than 0.001). Red blood cell 2,3-diphosphoglycerate (2,3-DPG) was significantly increased in the pregnant diabetic women (p less than 0.01), but the 2,3-DPG-induced change in hemoglobin-oxygen affinity was impaired. P50 (oxygen affinity, i.e., Po2 at 50% oxygen saturation) at actual pH correlated inversely with Hb Alc of the diabetic women (r = -0.45, p less than 0.05). The suggestion is made that, in diabetic pregnancy, particularly in poorly regulated cases, fetal hypoxia may be an important factor of the increased risk of intrauterine fetal death.

IMPAIRED OXYGEN RELEASE CAUSED BY ALTERATIONS OF THE METABOLISM IN THE ERYTHROCYTES IN DIABETES

Abstract In ambulatory, non-acidotic diabetics the oxyhaemoglobin-dissociation curve may be shifted to the left. In fifteen diabetics the average Po 2 for 50% saturated whole blood was 24·5 mm. Hg, which is significantly lower than normal (26·6 mm. Hg). The reasons for the increase in the oxygen affinity of the blood and the decrease in the oxygen-release capacity seem to be alterations in the carbohydrate metabolism in the erythrocyte of diabetics.

Does increased glomerular filtration rate or disturbed tubular function early in the course of childhood type 1 diabetes predict the development of nephropathy

To clarify whether glomerular hyperfiltration or disturbances in renal tubular function may be early markers of the later development of nephropathy a follow‐up study was performed in 34 young Type 1 diabetic patients, who had originally been investigated 12 years previously. The initial median age was 14 (range 7–18) years and median diabetes duration 7 (2–14) years. At initial examination only one of the 34 diabetic patients exhibited increased urinary albumin excretion rate. The median glomerular filtration rate was increased (136 vs 107 ml min−1 1.73 m−2; p < 0.0001) and median threshold concentration of phosphate per litre of glomerular filtrate was decreased (1.27 vs 1.76 mmol I−1; p < 0.0001) in the diabetic group as compared to that of 28 healthy children. At follow‐up 17 patients showed increased urinary albumin excretion rate and the median glomerular filtration rate in this group was significantly lower than that of 17 patients with normal urinary albumin excretion rate (108 vs 125 ml min−1 1.73 m−2; p < 0.05). However, no relationships were found between the increased urinary albumin excretion (incipient and/or overt diabetic nephropathy) at follow‐up to either the initial glomerular filtration rate (134 vs 137 ml min−1 1.73 m−2; p > 0.05) or to renal tubular function assessed from urinary excretion rate of β2‐microglobulin (0.059 vs 0.069 μg min−1; p > 0.05) and the renal threshold concentration of phosphate per litre of glomerular filtrate (1.29 vs 1.22 mmol I−1; p > 0.05).

The influence of maternal weight, smoking, vascular complications and glucose regulation on the birth weight of infants of type 1 diabetic women

The influence of maternal blood glucose regulation, weight gain, pre-pregnancy weight, vascular complications and smoking on the birth weight of infants was investigated in 72 type 1 (insulin-dependent) pregnant diabetic women. In patients with vascular complications (n = 23) the birth weight was significantly lower than in patients without vascular involvement (n = 49) (mean 380 g, P less than 0.05). The mean RBWR (relative birth weight ratio) of infants of patients who smoked more than 10 cigarettes per day was statistically significant lower compared to the mean RBWR of infants of non-smokers (P less than 0.025). A significant correlation was present between haemoglobin A1c (HbA1c) and RBWR (r = 0.28, P less than 0.02) and between maternal net weight gain and RBWR (r = 0.36, P less than 0.005) and this correlation became even stronger when only patients without vascular lesions were considered (n = 49) (r = 0.51, P less than 0.005) and (r = 0.50, P less than 0.005), respectively. In contrast no correlation was found between pre-pregnancy weight and RBWR. The study suggests that factors other than maternal hyperglycaemia stimulate fetal growth and may explain why fetal macrosomia may occur despite of strict blood glucose regulation.

Dysfunction of tubular phosphate reabsorption related to glomerular filtration and blood glucose control in diabetic children.

SummaryThe renal handling of inorganic phosphate was studied by measuring the urinary excretion rate of phosphate (

Hemoglobin AIc and red cell oxygen release capacity in relation to early retinal changes in newly discovered overt and chemical diabetics

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