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Biomedical subjects

J J Kjaergaard

Publications and source records attributed to J J Kjaergaard.

At least 19 recordsLinked to original sources

Development of insulin antibodies, metabolic control and B-cell function in newly diagnosed insulin dependent diabetic children treated with monocomponent human insulin or monocomponent porcine insulin.

One hundred and thirty eight patients participated in a two-year randomized, double-blind multicentre trial to compare monocomponent human insulin and porcine insulin in the treatment of newly diagnosed insulin dependent diabetic children with respect to development of insulin antibodies, metabolic control and B-cell function. There was no difference between the two patient groups throughout treatment either in the level of IgG insulin binding or the percentage of patients with insulin antibodies (IgG-insulin greater than 0.012 U/l). However, the estimated mean of log insulin binding values in the antibody positive patients alone was significantly lower (p less than 0.05) in the human insulin treated group at all times apart from 1 and 18 months (e.g., human insulin group at one and two years: 0.104 and 0.152 U/l, porcine insulin group at one and two years: 0.162 and 0.212 U/l). The insulin antibodies in both patient groups bound equivalent amounts of human and porcine insulin tracer. Metabolic control, insulin dosage and B-cell function in the two treatment groups were similar throughout the treatment period. It is concluded that in newly diagnosed insulin dependent diabetic children monocomponent human insulin is slightly less immunogenic than monocomponent porcine insulin, and equally effective in overall metabolic control.

Animals

The effect of buflomedil in diabetic retinopathy estimated by ocular fluorophotometry.

Tissue hypoxia is thought to be one of the possible factors involved in the etiology of diabetic retinopathy. Buflomedil has been reported to improve microvascular perfusion with a secondary increase in tissue oxygen pressure and may therefore be of interest in the study of diabetic retinopathy. We investigated 10 males with insulin-dependent diabetes and non-proliferative retinopathy, aged 24-46 with a duration of diabetes of 5-31 years. Buflomedil, 600 mg daily, or placebo was given for 4 weeks in a randomized, double-blind cross-over design, with a one-week washout in between. Patients were studied initially and at the end of each of the three periods. Ocular fluorophotometry was performed at each visit and a penetration index (PI) calculated by dividing the ocular measurements with the preceding average free fluorescein concentration. There was a slight, but significant decrease in the PI of the posterior vitreous while on buflomedil, from 10.6 +/- 13.4 (mean +/- SD) to 8.8 +/- 9.6 10(-4), p less than 0.05. No measurable changes were found in metabolic control as estimated by HbA1, and no side effects were observed. That the drug may act by increasing blood flow, was illustrated by measurements on capillary blood, where pH increased (7.43 +/- 0.01 to 7.45 +/- 0.01, p less than 0.05) and pCO2 decreased (5.48 +/- 0.4 to 5.15 +/- 0.24 kPa, p less than 0.05). Buflomedil may reduce the permeability of the posterior ocular barriers in diabetic retinopathy.

Adult

Microscopic appearance of the esophageal mucosa in a consecutive series of patients submitted to upper endoscopy. Correlation with gastroesophageal reflux symptoms and macroscopic findings.

The histologic finding of basal-layer hyperplasia and papillosis as consequences of gastroesophageal reflux still constitute an area of controversy. Consequently, a prospective study of symptoms and endoscopy and biopsy interpretation was undertaken in 200 patients consecutively submitted to upper endoscopy, whereof 12 were excluded. Complete agreement among all three variables was found in half of the patients and harmony between two of the variables in one fourth. In the last fourth the outcome was positive in one variable only, equally distributed among the symptoms, endoscopy, and histology. It is concluded that histology is of considerable value in gastroesophageal reflux disease.

Esophagoscopy

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

Ocular fluorophotometry in insulin-treated diabetic patients with and without retinopathy.

To look for possible determinators of the pathological readings of vitreous fluorophotometry in diabetes reported by other groups, we studied 32 insulin-treated patients, 22 of whom had fluorescein angiograms without pathological changes, while 10 had background retinopathy. 14 healthy subjects matched for age and blood pressure served as controls. Sodium fluorescein, 17 mg/kg body weight, was injected intravenously and ocular fluorophotometry performed 60 and 120 minutes later. Blood drawn 5, 45 and 120 minutes after the injection was assayed for total and ultrafiltrable fluorescein and the intraocular readings corrected for average preceding free plasma fluorescein. Patients without retinopathy did not differ from controls in any intraocular measure, while patients with retinopathy showed significantly increased readings in the posterior (60 min: 12 +/- 7 vs. 6 +/- 4, p less than 0.01, 120 min: 26 +/- 35 vs. 11 +/- 5, p less than 0.05) and middle vitreous (60 min: 6 +/- 3 vs. 3 +/- 3, p less than 0.001, 120 min: 11 +/- 5 vs. 8 +/- 5, p less than 0.01 (X 10(-9) g/ml fluorescein, mean +/- SD)). No significant relations to systolic or diastolic blood pressure, blood glucose, hemoglobin Alc or serum creatinine were found in any of the diabetic groups. Re-examination of 7 patients 4-14 days later in a non-fasting state showed no significant changes.

Adult

Some methodological problems in ocular fluorophotometry.

Facing conflicting results from centers working with vitreous fluorophotometry, we performed a series of methodological studies of the technique preceding clinical studies. A major problem is the resolution power of the system. This is predicted to be dependent on the size of the fiberoptic probe, the slit width and angle between incident and detecting light beam, which is shown to be true in experiments with glass cuvettes and in studies of the eyes of 10 healthy volunteers. In the in vivo studies, variations of slit height could also influence readings. The selection of appropriate filters is important to reduce reflexes and autofluorescence of the ocular media, which otherwise must be accounted for.

Adolescent

Some aspects of the pharmacokinetics of fluorescein in normal and in diabetic subjects.

A method for measuring the free fraction of fluorescein in plasma by ultrafiltration is tested. The coefficient of variation is 3%. Changes in pH and temperature from in vivo conditions at 37 degrees C to in vitro conditions are slight (less than 6%) and tend to minimize each other. To study the pharmacokinetics of fluorescein, 25 control subjects and 38 insulin-treated diabetics were examined after an intravenous injection of sodium fluorescein, 17 mg/kg body weight. 5, 45 and 120 min later, free fluorescein was significantly lower in the diabetics (5 min: 2.4 +/- 0.5 vs. 2.1 +/- 1.0, 45 min: 0.62 +/- 0.13 vs. 0.52 +/- 0.14, 120 min: 0.27 +/- 0.07 vs. 0.17 +/- 0.07 X 10(-5) g/ml, p less than 0.01 (mean +/- SD)). The renal excretion of fluorescein is reflected in a positive relation between serum creatinine and total plasma fluorescein at 45 and 120 minutes in the group of diabetics (Spearmans rho = 0.52, p = 0.04 and 0.53, p = 0.08, respectively).

Blood Glucose

Ocular fluorophotometry in normal subjects.

Leakage of fluorescein to the vitreous has been reported in diabetes and systemic hypertension. We have done detailed studies in normal subjects to look for determinators of possible leakage in this population. Twenty-nine healthy males, aged 18-67 years, were studied in the morning after an overnight fast. Fluorescein 17 mg/kg body weight was injected intravenously and blood drawn 5, 10, 15, 30, 45, 75 and 120 minutes later for measurement of ultrafiltrable fluorescein. Ocular fluorophotometry was performed before, 60 and 120 min after the injection. Mean fluorescein (+/- SD) in the posterior vitreous was 8.1 (+/- 5.5), middle vitreous 4.7 (+/- 6.0) and aqueous 240 (+/- 142) ng/ml after 60 minutes. At 120 minutes, a significant increase to 12.2 (+/- 8.6), 9.4 (+/- 9.3) and 317 (+/- 139) ng/ml was found in the three regions, p less than 0.05. At 60 minutes, age related significantly to posterior and middle vitreous concentrations, Spearmans rho = 0.49 and 0.61, as well as to aqueous concentrations, rho = 0.51 (p less than 0.01). Blood pressure related only to aqueous concentrations, at 60 minutes, rho = 0.42, p less than 0.05. When the intraocular measurements were corrected for average preceding ultrafiltrable fluorescein, age remained significantly related only to vitreous readings and blood pressure to aqueous readings.

Adolescent

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

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

Hemoglobin A1c as an indicator of long term blood glucose levels in diabetics with special reference to diabetic pregnancy.

Hemoglobin A1c in diabetics has been shown to be an index of average blood glucose levels in the preceding 1-2 months. We confirm this relationship in a group of 12 insulin-treated diabetics and extend it to 16 pregnant insulin-treated patients as well. Lower levels of HbA1c in pregnancy could be explained by better control. In an ongoing sequential study of 5 pregnant diabetics home-monitoring their blood glucose, we have an impression, that this relationship holds true for individual patients. If this is confirmed, the level of glycosylated hemoglobins in pregnancy may be used as a warning signal for deterioration of glucose control in out-patients.

Blood Glucose

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

The average Hb A1c concentration in consecutive cases of newly discovered nonacidotic diabetics was 11.4% prior to diet and insulin, as compared to 5.5% following prolonged optimal control (p less than 0.001). Hemoglobin A1c was significantly correlated with fasting blood sugar. In a controlled study the average Hb A1c in 30 subjects with chemical diabetes was 5.8% as opposed to 5.3% in controls with normal OGTT (p less than 0.05). Thirty-seven percent of the chemical diabetics had Hb A1c values greater than or equal to 6.5%, while none in the control group showed such high values. Hb A1c in whole blood has increased oxygen affinity. A decrease in red-cell oxygen release was noted in some untreated nonacidotic diabetics, and an adverse effect of insulin on the oxygen release capacity was demonstrated in both newly diagnosed ketoacidotic and nonacidotic diabetics. The importance of this defect in red-cell oxygen-releasing capacity on the function of the microcirculation is discussed. Signs of an early breakdown of the blood-retinal barrier was demonstrated in 20% of the chemical diabetics by fluorescein angiography.

Blood Glucose

Hemoglobin AIc as an index of long-term blood glucose regulation in diabetic pregnancy.

To evaluate hemoglobin AIc (Hb AIc) as an indicator of prolonged glucose control in pregnant diabetics, four groups of subjects were studied--16 pregnant diabetic, 13 pregnant nondiabetic, 12 nonpregnant diabetic, and 18 healthy control subjects. Hb AIc was significantly lower in the pregnant diabetic than in the nonpregnant diabetic subjects, 7.8% +/- 1.6 vs, 9.9% +/- 1.9 (mean +/- SD). No difference was present in the nondiabetic groups (4.0% +/- 0.7 vs. 4.3% +/- 0.8, respectively). Hb AIc correlated significantly with the average glucose concentrations of the preceding 60 days in both diabetic groups, suggesting that the lower concentration of Hb AIC in pregnant as compared with nonpregnant diabetic patients was because of better control of blood glucose. This was also borne out by the average of fasting glucose levels being 6.1 +/- 1.7 mmol/L in the pregnant diabetic and 10.7 +/- 2.2 mmol/l in the nonpregnant diabetic subjects.

Blood Glucose