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Biomedical subjects

J Nerup

Publications and source records attributed to J Nerup.

At least 235 records · Page 13Linked to original sources
PubMed1981

HbA1c and the diagnosis of diabetes mellitus.

To evaluate the usefulness of haemoglobin A1c (HBA1C) determinations in the diagnosis of diabetes mellitus, the outcome of a standard oral glucose tolerance test (OGTT) and HbA1c values were compared in 178 consecutive subjects referred for a diagnostic OGTT. The subjects were mainly in age groups in which non-symptomatic diabetes mellitus predominates. The prevalences of elevated fasting plasma glucose and abnormal OGTT were found to increase with increasing age. One third of the total series had impaired or diabetic OGTT. In the group with normal OGTT, 16% had fasting plasma glucose concentrations above the upper normal limit, but the range of HbA1c values did not differ from that of healthy controls. In the group with impaired OGTTs (n = 20), elevated HbA1c values were found only in subjects with elevated fasting plasma glucose and the highest two-hour OGTT values (n = 4). In the group with diabetic OGTT, 86-94% had HbA1c values above the upper normal limit, and HbA1c was elevated in all subjects with a fasting plasma glucose higher than 10.5 mmol/l or a 2-hour OGTT glucose value above 14.4 mmol/l. Using the results of the OGTT as the true diagnosis, HbA1c had a diagnostic specificity of 0.78 and sensitivity of 0.96. Only subjects with a substantially reduced glucose tolerance may be diagnosed by HbA1c determinations.

Adolescent↗
PubMed1981

A review of HLA antigens in longstanding IDDM with and without severe retinopathy.

The hitherto published studies of HLA antigens in diabetic retinopathy are reviewed. The existence of HLA associated genes conferring susceptibility (or resistance) to the development of diabetic retinopathy has neither been proved nor ruled out. Possible explanations of the lack of unanimous conclusions are discussed. Further studies in caucasians and other ethnic groups are warranted: future studies should be internationally accepted, well-defined diagnostic criteria and classifications of diabetes and diabetic retinopathy, and study and control groups should be carefully matched for other genetic and nongenetic risk factors. Future studies should include HLA D/DR typing.

Diabetes Mellitus↗
PubMed1980

Rapid changes in chromatographically determined haemoglobin A1c induced by short-term changes in glucose concentration.

Chromatographically determined haemoglobin A1c concentration was measured during short-term (1-24h) changes in glucose concentration in vitro and in vivo. In vitro at 37 degrees C the HbA1c concentration increased with glucose concentration and time both in normal and diabetic erythrocytes. In normal erythrocytes incubated in 20--100 mmol/l glucose, the increases in the HbA1c concentration were maximal after 4--6 h and then stable for the next 18--20 h. During the first hour, increases in the HbA1c concentration were linear with time and on average 0.034% HbA1c x h-1 x mmol/l glucose-1. In erythrocytes, after a rapidly produced increase (2 h), HbA1c decreased to preincubation concentrations during a further incubation of the erythrocytes in a glucose-free medium at 37 degrees C for 4--6 h. The mean rate of linear decrease was 0.017% x h-1 x mmol/l glucose-1. After incubation of erythrocytes in 100 mmol/l glucose for 24 h, 1.3% HbA1c remained stable for 6 h in saline. The rapid increase in HbA1c concentration, as determined by chromatography, was not due to stable HbA1c (ketoamine linked glucose) as no increase was found in the HbA1c concentrations determined by the thiobarbiturate method. In juvenile diabetics controlled by an artificial beta-cell, rapid changes of blood glucose concentration (up to 20 mmol/l) resulted in increases in HbA1c concentration of as much as 1.9% within 12 h (mean 1.1%). Rapid in vivo increases in HbA1c concentration were reversible by normalization of the blood glucose concentration. That rapid changes in HbA1c may occur in daily diabetic life was evidenced by differences in HbA1c concentration between blood samples from out-patient diabetics incubated in saline for 16 hours at 4 degrees C and 37 degrees C (range of differences 0.2--1.4% HbA1c). The differences correlated to the blood glucose concentration at the time of sampling blood for HbA1c determination. Thus, incubation of blood at a low glucose concentration prior to determination of the glycosylated haemoglobin concentration may overcome interference from rapidly produced HbA1c.

Adolescent↗
PubMed1980

Genetic patterns in diabetes mellitus.

Diabetes comprises many syndromes whose only common feature is a high blood glucose level. Some are entirely genetic, some partially so, and others not at all. Perhaps the most important advance in the past 10 years is proof that insulin dependent diabetes is genetically different from the insulin independent form. Most progress has been made in unraveling the etiology of insulin dependent diabetes, although more information is needed before the mode of inheritance is finally settled. The last few years have produced a plethora of new facts about insulin dependent diabetes mellitus, providing geneticists, clinicians, and epidemiologists with the fascinating challenge of a disease with an apparently genetic susceptibility to external (environmental) triggers. Little progress has been made in the field of insulin independent diabetes, and one might safely predict that the diabetic syndrome will still produce some nightmares for researchers who take up the challenge of trying to unravel its various etiologies and methods of inheritance.

Adolescent↗
PubMed1980

Direct streptozotocin toxicity on dispersed mouse islet cells determined by [51]Cr-release.

Dispersed islet cells were prepared from collagenase-isolated lean mouse pancreatic islets by Dispase-II and subsequent mechanical treatment in calcium depleted media. An average yield of 600 cells per islet was obtained, 84% of the cells being beta-cells. Cells were incubated with radioactive chromium as a marker of cell viability. Optimal labelling of 1--2 cpm per cell was obtained by incubating 10(5) cells with 10(6) cpm of [51]Cr for 90 min. When islet cells were incubated with streptozotocin, this drug induced [51]Cr-release after a lag time of 2--4 hours. Furthermore, a positive correlation between streptozotocin concentrations and [51]Cr-release was found. This assay of cytotoxicity was highly reproducible and might be applicable in the study of other beta-cell damaging agents or autoimmune phenomena in the pathogenesis of diabetes.

Animals↗
PubMed1979

HLA studies in diabetics.

The studies of HLA in diabetes mellitus have strongly supported the subdivision into (at least) two genetically distinct groups: The juvenile onset (or perhaps better the insulin dependent) type DM, which shows a marked association to the HLA system, and the maturity onset type with a weak or no association to HLA. The HLA system has provided tools to test specific genetic models for the insulin dependent DM. A model involving one disease susceptibility locus closely linked to the HLA-loci and with a recessive susceptibility allele in linkage disequilibrium with some of the HLA factors has been proposed by others. This model cannot be totally rejected on the basis of the available data, but it is made less likely, especially because it leads to very low estimates of the penetrance which is discrepant from independent estimates, based both on studies on monozygotic twins and other families. In addition suggestive but not yet conclusive evidence of an excessive risk for HLA-Dw3/Dw4 heterozygotes is in conflict with this model.

Diabetes Mellitus↗
PubMed1979

The influence of the major histocompatibility complex (H-2) on experimental diabetes in mice.

Mice with different histocompatibility loci on an identical background genome (congenic resistant lines of mice) were used to study the possible influence of the histocompatibility complex on experimental diabetes. The major histocompatibility complex (H-2) was not found to influence the diabetogenic effect of encephalomyocarditis (EMC) virus. In contrast the glucose intolerance following heterologous and homologous immunization with pancreatic antigens appeared H-2 influenced. Antibodies against cell surface components on viable B-cells were present in serum from mice with glucose intolerance induced by homologous immunization. The results suggest that the susceptibility to experimental autoimmune diabetes in mice is influenced by the H-2 complex.

Animals↗
PubMed1979

Incidence of insulin-dependent diabetes mellitus (0--29 years at onset) in Denmark.

Incidence data from Denmark on the insulin-dependent diabetes mellitus in the age group 0--29 years have been collected in two different geographical areas (West and South Jutland plus Copenhagen and North Zealand). An incidence of 13.3 per 100,000 per year (range 12.5--13.6) was registered (N = 792). No difference was found between the two areas. The male incidence exceeded the female incidence by 25.4 per cent. The age distribution showed rising values until a peak in the early puberty with a decline until a rather constant level after puberty. From year to year a seasonal variation of onset was demonstrable with maximum in the winter and minimum in the summer for males only. Ascertainment was found to be between 87.7 and 98.6 per cent and the annual number of new insulin-dependent diabetics in Denmark in the age group 0--29 years can be calculated to 310-350.

Adolescent↗
PubMed1979

Subclinical hypothyroidism in Addison's disease.

Fourteen patients with Idiopathic Addison's disease (IAD) were studied in order to detect a possible subclinical hypothyroid state. All were clinically euthyroid with normal serum thyroxine (T4) and serum 3,5',5'-triiodothyronine (T3). Eleven had circulating thyroid microsomal antibodies in blood. The mean basal serum TSH was significantly higher than that of the control group but only three patients had values above the upper normal range. The mean value of serum T4 was decreased as compared to that of the normal persons, while serum 3,3',5'-triiodothyronine was elevated. 7.5 mU bovine thyrotrophin per kilogram body weight injected intravenously caused a rise in serum T3 not different from the response in normals. However, as well increasing serum TSH as increasing microsomal antibody titer correlated significantly to decreasing thyroidal release of T3. Our results suggest that clinically euthyroid patients suffering from IAD might have a beginning thyroidal insufficiency because of a progressive immunological damage of the thyroid.

Addison Disease↗
PubMed1979

HLA and insulin-dependent diabetes mellitus.

As suggested from clinical data and on the basis of human leukocyte antigen (HLA) data, insulin-dependent diabetes mellitus (IDDM) is a disease entity in itself and is different from non-insulin-dependent diabetes and other types of diabetes mellitus in aetiology and pathogenesis. HLA-B8 is associated with IDDM in all Caucasian populations studied, irrespective of the age of onset of the disease. HLA-B15 is associated with IDDM in populations of Northern European and British origin, while B18 seems to replace B15 in Southern European populations. IDDM is uncommon in populations where the HLA-B8 frequency is low, and in the Japanese IDDM occurs in association with Bw22. The HLA-Dw3 and Dw4 association with IDDM is stronger than that of the B alleles. Relative risks for B8 and B15 heterozygous and homozygous individuals are identical, i.e., no gene-dose effect exists. The relative risk of B8/B15 carriers is double that of relative risks of B8 and B15 alone, i.e., there are two IDDM-associated genes. The same applies to Dw3/Dw4 carriers. In families the phenotype IDDM segregates with a certain genotype, the diabetic proband's HLA haplotype. Only a small proportion of family members carrying the 'diabetic haplotype' develop IDDM.

Autoimmune Diseases↗
PubMed1978

Possible toxic effects of normal and diabetic patient serum on pancreatic B-cells.

Serum from normal blood-donors and juvenile diabetic patients inhibited Rb+ accumulation and stimulated release of 51Cr and insulin in suspensions of dispersed pancreatic islet cells prepared from ob/ob mouse islets, which are rich in B-cells. The effects indicate the presence of a B-cytotoxic factor in human serum. Serum from mouse and fetal calf also inhibited the islet cell accumulation of Rb+. Toxicity was not suppressed by treating serum with protein A-Sepharose and did not correlate with islet cell binding of fluorescent antibodies to human immunoglobulin. Whereas all sera inhibited Rb+ accumulation, 3 of 6 diabetic patient sera, but no blood-donor serum, made the cells fluoresce on exposure to the fluorescent antibodies. Supporting a dependence on complement, toxicity remained after dialysis, but was destroyed by treating serum with zymosan-A or heating at 56 degrees for 30 min.

Animals↗