[The effect of home blood sugar measurement on the regulation of insulin-dependent diabetes mellitus. A controlled clinical study].
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Adult↗
Biomedical subjects
J Ditzel
Publications and source records attributed to J Ditzel.
Diabetic oxygen-hemoglobin equilibrium curves evaluated by nonlinear regression of the Hill equation.
The oxygen-hemoglobin equilibrium curves ( OHECs ) were measured on whole blood samples from 131 individuals (33 normal and 26 diabetic adults and 30 normal and 42 diabetic juveniles) using a Radiometer Dissociation Curve Analyzer (DCA-1). All measurements were made in the morning following an overnight fast and without exogenous insulin. The saturation versus Po2 data were fitted to the Hill equation using a previously described nonlinear regression algorithm to yield the parameters describing the position (P50) and shape (n) of each OHEC . It was found that the Hill model could be used to describe OHECs of both normal and diabetic subjects. A small (approximately 10%) but significant decrease in P50 was found for the diabetic juveniles compared to normal juveniles. There appeared to be no change in P50 with diabetes in adults. However, in these diabetic subjects, the P50 had been increased by the somewhat elevated levels of 2,3-DPG. No difference in n was found between either group of diabetics and their corresponding group of normals but n was approximately 5% lower in juveniles than in adults. The ability of blood to release oxygen to tissue may be transiently impaired in diabetic juveniles because of the left shift of their OHECs .
Adult↗
Proximal glomerulo-tubular balance in patients with type 1 (insulin-dependent) diabetes mellitus.
To evaluate the glomerulo-tubular balance of sodium and water in the proximal tubules of diabetic patients with elevated glomerular filtration rate, the renal plasma clearance of lithium and the glomerular filtration rate (51Cr-EDTA plasma clearance) were determined simultaneously in 11 ambulatory Type 1 (insulin-dependent) diabetic patients (aged 25-35 years) with no evidence of diabetic nephropathy and in 10 age-matched healthy subjects. The renal plasma clearance of lithium, which is a measure of flow from the proximal tubule into the thin descending limb of the loop of Henle, did not differ between diabetic and control subjects (28.9 +/- 4.0 versus 28.3 +/- 5.1 ml/min per 1.73 m2 surface area, mean +/- SD), whereas the glomerular filtration rate in the diabetic patients was significantly higher than in the control subjects (136 +/- 10.2 versus 108 +/- 13.6 ml/min per 1.73 m2, p less than 0.001). The same held true for the fractional reabsorption rate in the proximal tubules (78.7 +/- 3.2 versus 73.6 +/- 4.9%, p less than 0.02). The results indicate that the elevation of the glomerular filtration rate in diabetic patients is associated with a parallel increase in the proximal reabsorption rate. This type of glomerulo-tubular balance implies that the flow of water and flux of sodium to the segments distal to the proximal tubule are kept constant during variations in the glomerular filtration rate.
Absorption↗
Blood-oxygen transport in first trimester of diabetic pregnancy.
Factors involved in blood-oxygen transport were studied in 46 pregnant women during the first trimester. All had type 1 (insulin-dependent) diabetes and comparisons were made with similar measurements from 19 non-diabetic pregnant women, also in the first trimester. The concentration of hemoglobin A1c (HbA1c) was significantly increased (7.6% versus 4.4%, p less than 0.01) and arterial oxygen saturation was decreased (0.95 versus 0.98 mol/mol, p less than 0.01) in the pregnant diabetics compared with the non-diabetics. The hemoglobin concentration was significantly elevated in the diabetic women (12.9 versus 12.1 g/100 ml, p less than 0.01). Even though the red cell 2,3-diphosphoglycerate content was the same in the two groups, and pH was significantly lower in the diabetic women, hemoglobin-oxygen affinity was slightly increased in the diabetic patients (P50 at actual pH: 26.2 versus 26.7 mmHg, p less than 0.05; P50 at pH 7.40: 27.0 versus 28.0 mmHg, p less than 0.01). The study has demonstrated certain modifications in the blood oxygen transport system in the first trimester of pregnancy of diabetic women that are possibly related to the presence of excess amounts of glycosylated hemoglobin with increased oxygen affinity. This disturbance in maternal oxygen transport, particularly when associated with diabetic vascular disease, may lead to episodes of fetal hypoxia. Such fetal hypoxia may be a pathogenetic factor for the development of congenital malformations in the outcome of diabetic pregnancy.
2,3-Diphosphoglycerate↗
Effect of smoking on red cell oxygen transport and release in diabetic pregnancy.
In order to investigate the effect of smoking on the red cell oxygen transport and release in pregnant diabetic women, 23 smokers and 23 non-smokers were studied in the third trimester. The two groups were comparable with regard to blood glucose regulation, as the median concentration of blood glucose and glycosylated hemoglobin (Hb A1c) did not differ. Red cell 2, 3-diphosphoglycerate (2, 3-DPG) levels were significantly lower in the smokers than in the non-smokers (16.5 vs 17.8 mumol/gHb, p less than 0.01). P50 of the oxyhemoglobin dissociation curve at actual pH and at pH 7.40 was also significantly lower in the smokers (25.9 vs 26.9 mmHg, p less than 0.01, and 26.5 vs 27.8 mmHg, p less than 0.01 respectively). Red cell 2, 3-DPG was significantly correlated with P50 at pH 7.40 (r = 0.73, p less than 0.001). Arterial oxygen saturation was reduced to the same degree in smokers and in non-smokers, as compared with healthy non-smoking pregnant women and no adaptive increase in the hemoglobin concentration occurred in the pregnant diabetic smokers. The study suggests that smoking in pregnant diabetic women impairs the adaptive increase in 2, 3-DPG associated with diabetes-induced hypoxia.
Adolescent↗
Red cell 2,3-diphosphoglycerate and hemoglobin--oxygen affinity during normal pregnancy.
The concentration of red cell 2,3-diphosphoglycerate (2,3-DPG), hemoglobin-oxygen affinity and other oxygen transport variables were determined during first, second and third trimester of normal pregnancy as well as 3 months post partum in 18 healthy women. The median concentration of red cell 2,3-DPG increased significantly from the first to the third trimester (16.1 to 17.0 mumol/gHb, p less than 0.01), whereas 2,3-DPG decreased significantly post partum (p less than 0.01). Normal pregnancy was also associated with relative anemia, a significant increase in arterial pH, hypocapnia and hypophosphatemia. The difference in hemoglobin concentration from the first trimester to 3 months post partum was correlated inversely with the difference in red cell 2,3-DPG content (r = -0.52, p less than 0.05). In spite of the variations in red cell 2,3-DPG, hemoglobin-oxygen affinity expressed as P50 at actual pH remained unchanged during pregnancy and post partum. The study suggests that the increased level of 2,3-DPG during pregnancy may in part represent compensation for physiologic anemia and also compensate for a factor leading to increased hemoglobin-oxygen affinity during pregnancy.
2,3-Diphosphoglycerate↗
Red cell 2,3-diphosphoglycerate and hemoglobin-oxygen affinity during diabetic pregnancy.
Factors involved in blood oxygen transport were measured serially in the first, second and third trimester of pregnancy in 23 insulin-dependent diabetic women. Twenty-six non-pregnant diabetic patients served as a reference group. Diabetic pregnancy was associated with relative anemia, a significant increase in arterial pH, and hypocapnia. The concentration of red cell 2,3-diphosphoglycerate was significantly higher in the first trimester of diabetic pregnancy compared with non-pregnant diabetics (median value 16.4 vs. 15.0 mumol/g hemoglobin, p less than 0.02) and increased gradually from the first to the third trimester (16.4 to 17.2 mumol/g hemoglobin, p less than 0.01). The hemoglobin A1c concentration decreased simultaneously from 8.1% to 7.3% (p less than 0.01). The level of hemoglobin A1c in the first trimester was significantly lower than that in the non-pregnant diabetic patients (8.1 vs. 9.3%, p less than 0.01). In spite of the increase in red cell 2,3-diphosphoglycerate content and the decrease in hemoglobin A1c, factors known to reduce hemoglobin-oxygen affinity, the position of the oxyhemoglobin dissociation curve remained unchanged during diabetic pregnancy: P50 at actual pH in the first trimester, was 26.0 mmHg; in the second trimester, 26.9 mmHg, and in the third trimester, 26.8 mmHg (NS). These values of P50 at actual pH were identical with the value in the non-pregnant group (26.6 mmHg). Other factors influencing hemoglobin-oxygen affinity, such as hemoglobin concentration, hydrogen ion concentration and arterial oxygen saturation remained unchanged during diabetic pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)
2,3-Diphosphoglycerate↗
Serum amylase during recovery from diabetic ketoacidosis.
To elucidate the mechanism of the hyperamylasaemia which is often found in diabetic ketoacidosis, 9 patients who were admitted in this disease state were studied. Blood samples were taken every 4 hours for the first 24 hours and thereafter daily for 7 days. Serum amylase concentration increased gradually in all patients, from 256 (65-1155) U/1 at the initial sampling to a maximum of 1160 (210-2670) U/1 20-24 hours later (p. greater than 0.01), median values with 95% confidence limits. Simultaneously, plasma inorganic phosphate concentrations decreased from a median value of 1.35 mmol/l to 0.45 mmol/l (p less than 0.01), and a significant negative correlation was found between the changes in these parameters in 5 patients. Isoenzyme analysis in 8 of the patients showed that hyperamylasaemia was of the "salivary type" in two and of the "pancreatic type" in two. None of the patients had clinical signs of pancreatitis. It is concluded that in diabetic ketoacidosis, the increase in serum amylase concentration observed in all patients is closely related to the action of insulin in the majority of these, and some possible mechanisms are discussed.
Adolescent↗
Glomerular hyperfiltration and blood viscosity in type I (insulin-dependent) diabetic subjects.
To investigate whether the increased glomerular filtration rate (GFR) in short-term diabetic patients is related to increased blood- or plasma viscosities, GFR [( 51Cr] EDTA-clearance), whole blood- and plasma viscosities were simultaneously determined in 16 insulin-dependent diabetic subjects, aged 11 to 34 years (duration of disease 0.1 to 8 years) and compared to the results in healthy subjects. Mean standard GFR +/- SD (that is, GFR corrected to body surface area of 1.73 m2) was significantly higher in the diabetics than in 16 age- and sex matched controls (142 +/- 26 ml/min vs. 123 +/- 18 ml/min, P less than 0.02). Blood viscosities at different shear rates and the plasma viscosity were not significantly different in the two groupes , although the plasma fibrinogen level was significantly elevated in the diabetics (376 +/- 60 mg%, vs. 289 +/- 37 mg%, P less than 0.001). No correlation was found between GFR and the viscosity measurements. The results of the present study do not support the suggestion that the increased GFR in short-term diabetics is related to changes in blood viscosity.
Adolescent↗
[Megaloblastic anemia caused by malabsorption of vitamin B12 during long-term metformin therapy].
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Aged↗
Characterization of oxygen-hemoglobin equilibrium curves using nonlinear regression of the Hill equation: parameter values for normal human adults.
Measurements of oxygen concentration versus PO2 in blood from 33 normal adults were fitted, using a special nonlinear regression analysis, to the Hill equation to obtain the parameters describing the position (P50) and shape (n) of each oxygen-hemoglobin equilibrium curve (OHEC). Data between 20% and 97% saturation were described well by this empirical two-parameter model. The mean (+/- SD) P50 and n were found to be 26.2 (+/- 0.8) torr and 2.50 (+/- 0.07), respectively, in good agreement with previously published values. Some normal individuals, however, deviated markedly from the averages indicating that the published values cannot be applied to everyone.
Adult↗
Correlation of serum unconjugated oestriol to red cell 2,3-diphosphoglycerate levels in diabetic pregnancy.
In order to evaluate the possible underlying factors for the increase in red cell 2,3-diphosphoglycerate content observed in late diabetic pregnancy, its relationship with serum unconjugated oestriol, human placental lactogen, haemoglobin and hydrogen ion concentrations was investigated in 42 pregnant diabetic women. A significant correlation was found between red cell 2,3-diphosphoglycerate and serum unconjugated oestriol (r = 0.54, p less than 0.001), whereas no correlation was present between 2,3-diphosphoglycerate and the following variables: arterial pH, haemoglobin concentration and human placental lactogen. The content of 2,3-diphosphoglycerate correlated significantly with haemoglobin-oxygen affinity expressed as P50 at pH 7.4 (r = 0.34, p less than 0.05). The results of this study indicate that serum unconjugated oestriol may participate in the regulation of red cell 2,3-diphosphoglycerate content and thereby of the maternal blood oxygen release to the fetus.
2,3-Diphosphoglycerate↗
Tubular reabsorption rates as related to elevated glomerular filtration in diabetic children.
To study renal tubular reabsorption and tubulo-glomerular balance in diabetic children, glomerular filtration rate (GFR) and tubular reabsorption rates of sodium, glucose, ultrafilterable calcium, and phosphate were measured during fasting in 26 ambulatory type I (insulin-dependent) diabetic children without clinical signs of microangiopathy (age 7-14 yr; duration of diabetes 3-14 yr). Similar measurements were made in 28 healthy school children (age 8-14 yr). Mean GFR in the diabetic children was significantly higher than in the normal children (138 versus 109 ml/min/1.73 m2, P less than 0.01). Mean tubular reabsorption rates of sodium, glucose, and calcium were significantly increased in the diabetic subjects (P less than 0.001). In contrast, tubular reabsorption rate of phosphate in the diabetic subjects was not enhanced. The renal threshold concentration of phosphate (TmPO4/GFR) was suppressed in the diabetic compared with the healthy subjects (1.23 versus 1.73 mmol/L, P less than 0.001). TmPO4/GFR was unrelated to circulating parathyroid and growth hormone concentrations but correlated inversely with the reabsorption rate of glucose (r = -0.53, P less than 0.01). Sodium reabsorption was closely correlated to GFR in both diabetic (r = 0.99, P less than 0.0001) and healthy subjects (r = 1.00, P less than 0.0001), and both groups showed identical regression lines. The tubular glucose reabsorption rate was independent of GFR in the diabetics. Tubular calcium and phosphate reabsorptions correlated equally well with sodium reabsorption and with GFR in the diabetic and healthy subjects (P less than 0.001). The maximal reabsorption of phosphate relative to GFR was lowered in the diabetic children.(ABSTRACT TRUNCATED AT 250 WORDS)
Absorption↗
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.
2,3-Diphosphoglycerate↗
Relationship between glycosylation of haemoglobin and the duration of diabetes: a study during the third trimester of pregnancy.
The relationship between blood glucose and glycosylated haemoglobin (HbAlc) had been investigated during an 8 week period in 53 Type 1 (insulin-dependent) diabetic women studied during the third trimester of pregnancy. Blood glucose estimations (fasting and 2h post-prandially) were made an average of 41 times in each patient during this period and HbAlc was determined once at the end of the study. There was a significant correlation between both the mean blood glucose over the preceding 8 weeks and the standard deviation of the fasting blood glucose with HbAlc (r = 0.69, p less than 0.001; r = 0.46, p less than 0.001, respectively). A "glycosylation index" was calculated for each patient (HbAlc divided by the mean blood glucose value). There was a significant correlation between the "glycosylation index" and duration of diabetes (r = 0.68, p less than 0.001). In contrast, there was no correlation between red cell 2,3-diphosphoglycerate and HbAlc or "glycosylation index". These findings suggest that increasing duration of diabetes influences the post-translational formation of HbAlc and that isolated HbAlc values need to be interpreted with caution in the pregnant diabetic.
2,3-Diphosphoglycerate↗
Dysfunction of tubular phosphate reabsorption related to glomerular filtration and blood glucose control in diabetic children.
The renal handling of inorganic phosphate was studied by measuring the urinary excretion rate of phosphate (UPO4V), phosphate-(Cr51) EDTA clearance ratio (CPO4/GFR) and maximal tubular reabsorption of phosphate per litre glomerular filtrate (TmPO4/GFR) during fasting in 26 ambulatory Type 1 (insulin-dependent) diabetic children without clinical signs of microangiopathy (age: 7-14 years; duration of disease: 3-14 years). Similar measurements were made in 28 healthy schoolchildren (age: 8-14 years). UPO4 V and CPO4/GFR were significantly enhanced in the diabetic children (p less than 0.001) and correlated with the degree of hyperglycaemia (p less than 0.005). TmPO4/GFR was significantly suppressed in the diabetic children (1.23 versus 1.73 mmol/l, p less than 0.001). This disturbance was neither related to changes in serum parathyroid hormone nor to growth hormone concentrations but was inversely correlated with the degree of hyperglycaemia (r = -0.61, p less than 0.001) and with tubular reabsorption of glucose (r = -0.53, p less than 0.01). In spite of the markedly lowered TmPO4/GFR in the diabetic subjects, the mean maximal (TmPO4) and absolute tubular phosphate reabsorption rates were equal to those of the 28 healthy subjects. Both in the diabetic and healthy subjects, these parameters were positively correlated with glomerular filtration rate which was significantly elevated in the diabetic children (138 versus 109 ml/min per 1.73 m2, p less than 0.01). The study demonstrates a dysfunction in tubular phosphate reabsorption in diabetic children which is related to glycaemic regulation.
Adolescent↗
The effect of etidronate disodium (EHDP) on retinopathy in insulin-dependent diabetic patients.
In a randomized double-blind study the effect of etidronate disodium (EHDP) on retinopathy, plasma inorganic phosphate and blood oxygen transport was assessed in 26 insulin-dependent diabetic patients. Following 6 months of EHDP administration, plasma inorganic phosphate had increased significantly (1.48 vs 1.14 mmol/l; P less than 0.01). Red cell, 2,3-diphosphoglycerate concentration (16.9 vs 15.1 mumol/g Hb; P less than 0.01) and the haemoglobin-oxygen affinity measured by pO2 at 50% oxygen saturation (P50) had also increased significantly (27.5 vs 26.3 mmHg; P less than 0.01). No changes had occurred in mean blood glucose and haemoglobin A1c concentrations, indicating a comparable degree of glucose regulation. Following 6 months of EHDP administration an association was found between improvement in retinopathy and the increase in plasma inorganic phosphate.
2,3-Diphosphoglycerate↗
Glomerular filtration rate and extracellular fluid volume in insulin-dependent patients with diabetes mellitus.
To investigate whether the increased GFR in diabetic patients is related t an increased ECV, GFR ([51Cr] EDTA clearance) and ECV (distribution volume of [51Cr] EDTA) was determined in 26 insulin-dependent diabetic men aged 17 to 50 years (duration of disease 0.1 to 14 years) and compared to the results in normal men. Mean standard GFR +/- SD (that is, GFR corrected to a body surface area of 1.73 m2) was significantly higher in the diabetics than in 26 age-matched controls (127 +/- 21 ml/min vs. 107 +/- 15 ml/min, P less than 0.001). The same held true for the renal function assessed as the ratio GFR/ECV (0.58 +/- 0.10 hr-1 vs. 0.51 +/- 0.07, P less than 0.05). Regression analysis showed that the relation between ECV and body weight and between ECV and body surface area was the same in the diabetic patients as in 44 controls. The increased GFR but normal ECV indicates that the GFR alteration in diabetic patients reflects a real hyperfunction.
Adolescent↗