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Biomedical subjects

H B Mortensen

Publications and source records attributed to H B Mortensen.

54 records · Page 3Linked to original sources
PubMed1984

Glucosylation of human haemoglobin A. Dynamic variation in HbA1c described by a biokinetic model.

The reaction kinetics for the reversible condensation of D-glucose and haemoglobin A through a labile haemoglobin A-aldimine adduct to HbA1c have been investigated using a biokinetic model. The specific rate constants obtained from in vitro experiments were included in the model which also took into account the removal of HbA1c by decay of erythrocytes. Using a sinusoidal variation in blood glucose a phase delay of about 2 hours was observed between the maximum blood glucose concentration and the maximum aldimine concentration. The mean haemoglobin A-aldimine concentration was independent of both the amplitude and frequency of the blood glucose oscillations and reached equilibrium concentration within 24 hours. The steady state relation between mean blood glucose and HbA1c was similar to the corresponding relation based on an irreversible formation of HbA1c. However, contrary to the irreversible model the steady state HbA1c concentration with the reversible model was reached 3 to 4 weeks after a change in blood glucose level. This finding is in agreement with clinical experience and indicates that in assessing continuous glycaemic control in diabetic patients haemoglobin A1c should be measured approximately every 3 to 4 weeks.

Blood Glucose↗
PubMed1984

Fetal growth delay and maternal hemoglobin A1c in early diabetic pregnancy.

Forty insulin-dependent diabetic women in the first trimester of pregnancy were studied. Fetal crown-rump length was measured by ultrasound and related to maternal hemoglobin A1c. Thirty mothers with normal size fetuses had an average hemoglobin A1c level of 7.8%. Ten mothers had fetuses that were smaller than normal (equivalent to eight to 14 days less growth) and also had higher hemoglobin A1c, 8.9% (P less than .05), indicating a more poorly controlled diabetes. Careful metabolic compensation in very early diabetic pregnancy should therefore be attempted to prevent induction of early fetal growth delay.

Birth Weight↗
PubMed1984

Variations in hemoglobin A1c and blood glucose in children with newly diagnosed diabetes mellitus described by a biokinetic model.

Hemoglobin A1c (HbA1c) and the blood glucose concentrations were measured in 26 children with newly diagnosed diabetes mellitus from the start of insulin treatment and during the remission and post-remission phases. The results were analysed according to a biokinetic model which describes HbA1c as a function of the preceeding blood glucose level during the lifetime of the erythrocytes. The correlation between HbA1c and blood glucose at the start of treatment improved significantly when the model was modified to accomodate a change in the blood glucose level at the time when the first diabetic symptoms were noticed. The individual HbA1c values measured after 1, 2 and 3 weeks of insulin treatment were compared with values predicted from the biokinetic model and preceeding blood glucose measurements. There was a significant positive correlation between observed and predicted values, and the correlation increased with the length of the observation period. In all children the HbA1c level declined and reached a nadir 10 to 15 weeks after initiation of treatment. A significant negative correlation between the duration of remission and the HbA1c level was observed. It is concluded that the biokinetic model compares favourably with the observed variations in HbA1c and blood glucose levels which occur in newly diagnosed diabetes mellitus during the first weeks of insulin treatment.

Adolescent↗
PubMed1983

Glucosylation of human haemoglobin a in red blood cells studied in vitro. Kinetics of the formation and dissociation of haemoglobin A1c.

We examined the stability of the ketoamine adduct, termed HbA1c, formed between the N-terminal valine of the haemoglobin A (HbA) beta chain and D-glucose using an isoelectric focusing method. Prolonged saline incubation of purified HbA1c followed by renewed isoelectric focusing revealed that the HbA1c concentration decreased while a corresponding increase in the HbA concentration occurred. The emergence of haemoglobin A on saline incubation indicates that the non-enzymatic glucosylation of haemoglobin A to HbA1c is a reversible process. This finding was further substantiated by kinetic studies on the formation and breakdown of the ketoamine adduct during incubation of red cells in glucose and saline. It appeared that the rate constant for the formation k2 was 14.2 X 10(-6) X s-1 at 37 degrees C while the rate constant for dissociation k-2 was 1.7 X 10(-6) X s-1. From these data an equilibrium constant K of 8.4 was calculated. This information should be of importance in interpretation of HbA1c levels during abrupt changes in diabetic control.

Adolescent↗
PubMed1983

Serum lipids and lipoproteins in 157 insulin dependent diabetic children and adolescents in relation to metabolic regulation, obesity and genetic hyperlipoproteinemia.

Serum lipids and lipoproteins were measured in 157 insulin dependent diabetic children and adolescents (IDDM) and in 350 healthy reference individuals. Serum triglyceride values were lower and total cholesterol and high density lipoprotein cholesterol higher in IDDM. Metabolic regulation reflected by glucosuria, postprandial blood glucose, number of hypoglycemic episodes and hemoglobin A1c all correlated strongly with serum triglyceride and very low density lipoprotein cholesterol. Serum lipids and lipoproteins did not correlate with obesity. Three children had genetic hyperlipoproteinemia. In IDDM measurement of serum lipids and lipoproteins can thus be used to further assess metabolic regulation. Measurement of serum lipids and lipoproteins seems warranted for future evaluation of the risk of cardiovascular disease in IDDM.

Adolescent↗
PubMed1983

Comparison of six assays for glycosylated haemoglobin determination.

To examine which glycosylated haemoglobin A components and which assays are the most useful in assessing long-term control in diabetic patients we have compared glycosylated haemoglobin concentrations in normal subjects and diabetic patients measured by six different methods, three chromatographic, a colorimetric, an isoelectric focusing and an agar gel electrochromatographic method. Despite the fact that the correlation between methods was high and the precision calculated from intra-assay variations acceptable, several differences in results were found. Thus Isolab columns determined lower values than other chromatographic methods and the unstable aldimine fraction interfered in agar gel electrochromatography. The increase in HbA1 in diabetics compared with normals was less than the corresponding increase in both HbA1c and total ketoamine bound glucose. This finding was consistent with the observation that the contribution of HbA1a + b fraction to HbA1 was constant at glucose concentrations above 10 mmol/l while a linear increase in these minor haemoglobins and consequently in HbA1 occurred at glucose concentrations below this level. We conclude that HbA1c' determined either by isoelectric focusing or ion exchange chromatography are the assays of choice for the determination of glycosylated haemoglobin in clinical routine.

Calorimetry↗
PubMed1982

Glycosylation of human hemoglobin A. Kinetics and mechanisms studied by isoelectric focusing.

The reaction between glucose and hemoglobin A (HbA) leading to hemoglobin A1c through a labile intermediate, designated anodal glycohemoglobin A, was studied in vitro using an isoelectric focusing method. Studies were performed on the kinetics of the formation and breakdown of the labile intermediate. The reactions of HbA with various aldohexoses and of hemoglobin A1c and anodal glycohemoglobin A with phenylhydrazine were studied. It is suggested that the glucose in the anodal glycohemoglobin A band is in the pyranose form of a Schiff base formed between the N-terminal amino group of the protein and D-glucose, while the fructose in hemoglobin A1c is in the pyranose form of the ketimine comprising also the N-terminal of the group. Elution peaks from ion-exchange chromatography of the hemoglobins termed HbA1a, HbA1b, HbA1c and HbA studied by isoelectric focusing revealed that: HbA1a formed two bands and HbA1b one band far toward the anode; both contained minor fractions of HbAlc and HbA; HbAlc appeared as a single band, while HbA was contaminated with some HbA1c. Hemoglobulin A1c purified by isoelectric focusing eluted as one peak when analysed by ion-exchange chromatography, while anodal glycohemoglobin A co-eluted with the first HbA1c fractions in the chromatogram. From kinetic studies it appeared that the rate constant for formation (k1) of anodal glycohemoglobin A was 0.096 . 10(-3) l/mol . s-1 at 37 degrees C. The constant for dissociation (k-1) was 0.10 . 10(-3) s-1. From these an equilibrium constant K of 0.96 l/mol was calculated. The apparent Arrhenius activation energies for the (k1) and (k-1) reactions were 42.5 and 47.5 kJ/degree, respectively. Consequently the equilibrium constant K is predicted to be nearly temperature-independent within the temperature range investigated. This was fully substantiated by experiments conducted at different temperatures. Furthermore, the values of the apparent Arrhenius activation energies allows the values of the rate constants to be calculated at any temperature within the experimental temperature range. This information is of importance for a closer understanding of the mechanisms of glycohemoglobin accumulation in red blood cells.

Blood Glucose↗
PubMed1982

Excretion of methimazole in human milk.

It is universally stated that antithyroid drugs are concentrated in human milk and are thus contraindicated during breast-feeding. We recently showed, however, that propylthiouracil (PTU) was not concentrated in milk and a study has now been made of the excretion of another widely used antithyroid drug carbimazole (CMI) in human milk. Methimazole (MMI) in blood and milk from five lactating women was measured after oral administration of CMI 40 mg, which is rapidly and completely transformed to the active antithyroid compound MMI. One hour after CMI, the mean serum-MMI reached 253 microgram/I and the mean concentration of MMI in milk reached 182 microgram/I. MMI was found to be unionized and not to be protein bound in serum, and it occurred in milk in the same concentration as the serum; the mean milk/serum ratio was 0.98. The mean total amount of MMI excreted in milk over 8 h was 34 microgram (SEM +/- 5, n = 5), i.e. 0.14% of the dose administered.

Administration, Oral↗
PubMed1982

Metabolic control in children with insulin dependent diabetes mellitus assessed by hemoglobin A1c.

The glycosylated hemoglobin component, hemoglobin A1c, was estimated in 92 children with insulin dependent diabetes mellitus by an iso-electric focusing procedure during an observation period of 18 months. A significant correlation between hemoglobin A1c and the actual metabolic control according to clinical ratings was found. A seasonal variation in the concentration of the hemoglobin A1c was observed with the lowest level in the months of June and July consistent with an improved metabolic control in the diabetic children during the summer period. A direct relationship was found between metabolic control as assessed by hemoglobin A1c and retarded linear growth expressed as standard deviation score for height. Children with poorly controlled diabetes (initial hemoglobin A1c level above 12.5%) improved their carbohydrate tolerance shown by a significantly lower glycohemoglobin level at the end of the observation period. Consequently, hemoglobin A1c is particularly useful in the routine management of insulin dependent diabetic children in poor metabolic control. Frequent determinations are necessary since in these patients the glucose profiles are prone to great variations, which may lead to changes in the hemoglobin A1c concentration of about 1% in a week.

Adolescent↗
PubMed1981

Determination of haemoglobin A1c by iso-electric focusing. Effect of incubation of erythrocytes and comparison of results obtained by ion-exchange chromatography.

Blood samples from 24 non-diabetics and 26 diabetics were analysed using both thin layer iso-electric focusing and ion-exchange chromatography. Using isoelectric focusing it was found that about 10% of haemoglobin A1c (0.7-1.2% of total haemoglobin) could be removed by a preceding incubation of the erythrocytes in saline at 37 degrees C for 6 h. When glucose was added to the incubation medium in a final concentration of 25 mmol/l no decline was seen in the concentration of haemoglobin A1c. Using similar treatment of erythrocytes identical results were obtained by the two methods. A reference interval for normal subjects (age range 6 months to 65 years) was established for the iso-electric focusing method using non-incubated samples.

Chromatography, Ion Exchange↗
PubMed1980

Quantitative determination of hemoglobin A1c by thin-layer isoelectric focusing.

A method for the quantitation of hemoglobin A1c using isoelectric focusing is reported. Hemolysates were prepared and stabilised with carbon monoxide and with potassium cyanide before the quantitation. The two preparations gave identical results. The potassium cyanide method is simple and adequate for routine purposes, but the cyanohemiglobin compound remains stable for one week only. The carbon monoxide method is more laborious, but the carboxyhemoglobin remains stable for up to one year. Quantitations of the separated fractions emerging after isoelectric focusing were made with spectrophotometry or with densitometry. No significant difference in the results could be shown. Reproducibility tests were improved by introducing transferrin as an internal standard. The specificity of the method was checked by the in vitro addition of oral hypoglycemic drugs and of insulin.

Carbon Monoxide↗
PubMed1979

Kinetics of propylthiouracil in the elderly.

The pharmakokinetics of propylthiouracil was evaluated in 9 elderly patients and compared to previous results from 6 younger subjects. By giving the drug both by the intravenous and oral route of administration it was possible to estimate the rate and extent of bioavailability. The various kinetic parameters were calculated according to a two-compartment model by use of two different methods: a graphical hand drawn one and by a special developed computer program based on a least squares minimalisation. While no significant differences could be demonstrated between the two age groups concerning volumes of distribution, clearance and extent of absorption, a large difference was found with regard to the absorption rate constant ka, which was about 3 times higher in the younger than in the elderly subjects, presumably due a reduced gastric emptying time. Considering the comparison between the two methods of calculations all the kinetics parameters were similar except ka and the slow disposition rate constant betw which were underestimated by the graphical method. It is concluded that no-age dependent changes exist concerning the kinetics of propylthiouracil except for a decreased rate of absorption. Graphical methods in pharmacokinetics are useful in obtaining distribution and elimination data but seem often biased for the evaluation of absorption rate constants.

Age Factors↗
PubMedDate not supplied

A 6-year nationwide cohort study of glycaemic control in young people with type 1 diabetes. Risk markers for the development of retinopathy, nephropathy and neuropathy. Danish Study Group of Diabetes in Childhood.

The study aimed to identify risk markers (present at the start of the study in 1989) for the occurrence and progression of microvascular complications 6 years later (in 1995) in a Danish nationwide cohort of children and adolescents with Type 1 diabetes (average age at entry 13.7 years). Probabilities for the development of elevated albumin excretion rate (AER), retinopathy, and increased vibration perception threshold (VPT) could then be estimated from a stepwise logistic regression model. A total of 339 patients (47% of the original cohort) were studied. Sex, age, diabetes duration, insulin regimen and dose, height, weight, HbA(1c), blood pressure, and AER were recorded. In addition, information on retinopathy, neuropathy (VPT), and anti-hypertensive treatment was obtained at the end of the study. HbA(1c) (normal range 4.3-5.8, mean 5.3%) and AER (upper normal limit <20 microg min(-1)) in two, timed overnight urine collections were analysed centrally. Eye examination was performed by two-field fundus photography. Determination of VPT was assessed by biothesiometry. Increased AER (> or =20 microg min(-1)) was found in 12.8% of the patients in 1995, and risk markers for this were increased AER and high HbA(1c), in 1989 (both p<0.001). Retinopathy was present in 57.8% of patients in 1995, for which the risk markers were long duration of diabetes (p<0.0001), age (p<0.01), and high HbA(1c) (p<0.0001) in 1989. Elevated VPT (>6.5 V) was found in 62.5% of patients in 1995, for which the risk markers were male sex (p<0.05), age (p<0.0001), and increased AER (p<0.05) in 1989. This study confirms that hyperglycaemia plays a major role for the development of microvascular complications in kidneys and eyes, and emphasises the need for optimal glycaemic control in children and adolescents with Type 1 diabetes.

Adolescent↗