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J Nerup

Publications and source records attributed to J Nerup.

At least 217 records · Page 12Linked to original sources
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

Possible association between DNA sequences flanking the insulin gene and atherosclerosis.

The proportion of subjects homozygous for DNA restriction fragments of a large size class (U alleles), in the polymorphic region flanking the 5' end of the insulin gene of chromosome 11, was higher in a group of non-insulin-dependent diabetic (NIDDM) patients than in normal controls. This finding confirms that the U allele is associated with at least one form of NIDDM. The U alleles were also found to be strongly associated with macroangiopathy in diabetic as well as in non-diabetic subjects. Thus, DNA sequences contained in the U alleles might be associated with the development of atherosclerosis in an as yet unknown way.

Alleles↗
PubMed1982

DNA insertion sequences near the insulin gene affect glucose regulation.

There is restriction-fragment length polymorphism in the 5'-flanking region of the insulin gene on the short arm of chromosome 11 in man. The polymorphic DNA sequences in 53 members of a large family were analysed by means of the restriction endonuclease BglI. In this family, the BglI restriction fragments were found in four sizes--2.8 kilobases (kb), 2.9 kb, 4.6 kb, and 4.8 kb. They segregated as alleles. The two larger BglI restriction fragments (U alleles) were associated with high haemoglobin Alc levels in both blood-related and unrelated non-diabetic members of the family.

Adolescent↗
PubMed1982

Glycosylated haemoglobin and steady-state mean blood glucose concentration in Type 1 (insulin-dependent) diabetes.

Since glucose control and glycosylated haemoglobin varies asyncroneously, we have studied the steady-state relationship between these two factors. In Type 1 (insulin-dependent) diabetic patients with a constant haemoglobin A1c during the preceding 2 years, 15 ambulatory blood glucose profiles during a 5-week period showed a constant glucose level and provided a precise estimate of the mean blood glucose concentration. In addition, we studied 15 non-diabetic subjects who provided three glucose profiles and had one haemoglobin A1c determination performed. A good correlation was found for a curvilinear relationship (haemoglobin A1c = 2.07 X mean blood glucose0.596, r = 0.98). This close relationship indicates that glycosylated haemoglobin is a valuable, but not very sensitive, index of glucose control.

Adolescent↗
PubMed1982

The low dose streptozotocin murine model of type 1 (insulin-dependent) diabetes mellitus: studies in vivo and in vitro of the modulating effect of sex hormones.

The influence of sex on pancreatic islet B cell susceptibility to streptozotocin was studied in mice given multiple low doses of streptozotocin. Male C3 D2 F1 mice developed a steadily increasing blood glucose level after a lag period of about 3 weeks, in contrast to females who were resistant. Spleen cells from streptozotocin treated female animals produced hyperglycaemia in total body irradiated syngeneic female recipients, but only if the recipients were treated with testosterone. Testosterone treatment of donors did not affect blood glucose levels of recipients. Streptozotocin cytotoxicity in vitro determined by a 51Cr-release assay revealed an increased sensitivity to streptozotocin in dispersed islet cells from adult male animals as compared with cells from adult female mice. The incubation of islet cells from animals of either sex with testosterone, or oestradiol plus progesterone, did not enhance the susceptibility to streptozotocin. Islet cells from sexually immature male or female mice were less susceptible to streptozotocin. The results demonstrate that sex determines susceptibility to streptozotocin in vivo and in vitro.

Animals↗
PubMed1982

Absence of H-2 genetic influence on streptozotocin-induced diabetes in mice.

Five daily injections of streptozotocin (40 mg/kg) produced a delayed but progressively increasing level of hyperglycaemia in long term studies with male Naval Medical Research Institute mice and C3D2F1 (DBA 2 J male x C3H/Tif female) F1 hybrid mice. The development of hyperglycaemia was paralleled by decreased amounts of pancreatic immunoreactive insulin as well as degranulation and necrosis of pancreatic B cells. Insulitis was found from days 9-25 after the first injection of streptozotocin. Compared with the F1 hybrid strain the parental inbred strains DBA 2 J and C3H/Tif demonstrated a certain resistance to streptozotocin. Development of hyperglycaemia did not differ in four congenic resistant lines of mice on the C57 BL/10 genetic background, indicating the major histocompatibility complex genes are not likely to determine susceptibility to streptozotocin-induced islet B cell damage.

Animals↗
PubMed1982

Neutrophil and lymphocyte function in patients with diabetes mellitus.

Neutrophil granulocyte chemotaxis and intraneutrophilic and plasma levels of lysozyme as well as the number of T and B lymphocytes and lymphocyte transformation in vitro on stimulation with mitogens and microbial antigens were studied in four groups of patients with diabetes mellitus (DM). Twelve patients with insulin-dependent diabetes mellitus (IDDM) and ketoacidosis and 4 patients with non-insulin-dependent diabetes mellitus were studied at the time of diagnosis and before and after start of treatment. Ten patients with IDDM of less than 10 years' duration which had been difficult to regulate well and 10 patients with IDDM well regulated for more than 20 years were studied at their regular outpatient visits. Apart from a slight increase in plasma lysozyme in group 1 from the first to the second examination, we found no differences between diabetics and healthy control persons. It is concluded that if patients with DM are more susceptible to infections, it is probably caused by elements of neutrophil or lymphocyte function not examined in this study or by factors unrelated to immunity.

Adolescent↗
PubMed1982

Restriction fragment length polymorphism of the insulin gene in diabetes mellitus.

Variant DNA sequences flanking the human insulin gene were found in the Danish population using restriction endonucleases (restriction fragment length polymorphism). The frequencies of these DNA sequences were determined in 47 non-insulin-dependent diabetics and 93 control individuals. We report an association between a restriction fragment length polymorphism of the insulin gene and NIDDM.

Base Sequence↗
PubMed1982

HLA and diabetes.

HLA studies have conclusively demonstrated that IDDM and non-IDDM are separate disease entities. A considerable part of the genetic susceptibility to IDDM is due to one or more HLA genes. The HLA-DR3 and -DR4 factors showing the strongest association with IDDM belong to the so-called DR antigens, which are believed to be the immune response determinants of man. A dominant model for the HLA-controlled susceptibility to IDDM has been ruled out and a recessive model seems unlikely. A gene-dose model intermediate between dominance and recessivity is still possible, but there is also some evidence against this model, because DR3/4 heterozygotes seem to have a considerably higher risk of developing IDDM than has DR3/3 and DR4/4 homozygotes. It has been suggested that DR3 (or a DR3-associated factor) and DR4 (or a DR4-associated factor) confer susceptibility to IDDM each by a separate mechanism, and more recently that DR3/4 heterozygotes may carry combinatorial antigens which could contribute to the susceptibility to IDDM. Studies of HLA-associated clinical heterogeneity within IDDM are indicated to gain further insight in the genetics of IDDM.

Diabetes Mellitus↗
PubMed1981

HLA-D and -DR antigens in genetic analysis of insulin dependent diabetes mellitus.

Three groups of patients with insulin-dependent diabetes mellitus, ascertained by different procedures, were investigated for HLA-A, B, C and D antigens (n = 164), and a subset (n = 93) for HLA-DR. Both HLA-D/DR3 and D/DR4 were strongly positively associated and D/DR2 was negatively associated with insulin-dependent diabetes. HLA-DR+ was found to be a better marker for insulin-dependent diabetes than Dw4. The HLA-B associations (B8, B15 and B18) were clearly secondary to the increases of HLA-D/DR3 and D/DR 4. The HLA associations did not differ between familial and isolated cases indicating that these two groups may well have a common genetic background. Based on analysis of HLA-haplotype sharing in affected sibling pairs, a simple dominant model of inheritance could be ruled out, and a simple recessive model was found unlikely. The relative risks for the HLA-Dw3,4 and HLA-DR3,4 phenotype were 21.2 and 44.4 respectively and exceeded those of both the HLA-Dw3 and HLA-DR3 (5.6 and 4.3) as well as the HLA-Dw4 and DR4 (10.1 and 10.5) phenotypes. This argues against an intermediate genetic model but further studies are needed to clarify whether there is more than one susceptibility gene for insulin-dependent diabetes mellitus within the HLA-system.

Diabetes Mellitus↗
PubMed1981

Prevalence of diabetic autonomic neuropathy measured by simple bedside tests.

To investigate the prevalence of diabetic autonomic neuropathy, five simple bedside tests, beat-to-beat variation during quiet respiration, beat-to-beat variation during forced respiration, heart rate and blood pressure response to standing, heart rate response to exercise, and heart rate response to Valsalva's manoeuvre were applied to 75 male insulin-dependent diabetics, mean age 40 years, (range 30-49 years). The subjects were subdivided into three groups according to duration of diabetes, which was between 0 and 40 years. Twenty-eight healthy age-matched male controls were also studied. The prevalence of diabetic autonomic neuropathy in the whole diabetic population indicated by abnormal response in beat-to-beat variation during forced respiration was 27%. Diabetic autonimic neuropathy increased in frequency with duration of disease. Patients with nephropathy or proliferative retinopathy had a significantly higher prevalence of diabetic autonomic neuropathy as indicated by abnormal beat-to-beat variation during forced respirations (p less than 0.01) than patients without these complications.

Adult↗
PubMed1981

Synthesis of glycosylated haemoglobin in vivo.

The synthesis of glycosylated haemoglobins in vivo was measured during 24 h of controlled hyperglycaemia in seven insulin dependent diabetics. The mean blood glucose concentration was 22 mmol/l, while electrolytes and other metabolites were kept normal by infusion of 4-23 IU of insulin during hyperglycaemia. The study confirmed the velocity and magnitude of unstable HbAlc formation previously found in vitro. The stable HbAlc formed in 24 h was an average 0.006% of total haemoglobin/mmol glucose. This compares well with the rate of HbAlc synthesis reported in normal subjects using 59Fe-kinetic measurements, and is in accordance with the concept of slow changes in stable HbAlc with time and glucose concentration. To investigate the possibility that the rate of HbAlc synthesis varies with erythrocyte age, glycosylated haemoglobins were measured in erythrocyte fractions after density separation on Percoll-Albumin gradients. We found both in normal subjects and in insulin treated diabetics that the 5% least dense cells contained 70%-80% of whole blood HbAlc. Assuming the least dense cells to be the youngest erythrocytes, this observation is inconsistent with a slow linear increase in HbAlc. Similar results were obtained in six newly diagnosed insulin dependent diabetic patients both before and after the first 30 days of insulin treatment, even though a marked decrease in young cell HbAlc would be expected with the improved glucose control observed. We therefore conclude that density separation of erythrocytes is an inadequate technique to study age related HbAlc synthesis.

Adult↗
PubMed1981

Autoimmunity in insulin-dependent diabetes mellitus.

Genetic susceptibility, environmental factors and immune mechanisms are implicated in the pathogenesis and etiology of insulin-dependent diabetes mellitus. The onset of the disease is associated with a major loss of beta cells, and inflammatory cells may be seen in and around the islets of Langerhans. Insulin-dependent diabetes is often associated with autoimmune endocrinopathies. Antipancreatic cell-mediated autoimmunity is found predominantly in young patients with insulin-dependent diabetes of recent onset as are antibodies reactive with cytoplasmic components or cell surface determinants of islet cells. Antibodies reactive with live islet cells may mediate complement-dependent cytotoxicity. The antigen(s) in the islet cells remain(s) to be identified and characterized. Further studies will be necessary to determine whether autoimmunity is the cause of beta-cell destruction or whether it is a consequence of damages caused by exogenous agents in susceptible persons.

Animals↗