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  • 1
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes ; islet cell antibodies ; fasting C-peptide ; insulin dosage ; prospective analysis ; fasting blood sugar
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A cohort of 82 patients with Type 1 (insulin-dependent) diabetes was followed prospectively for 24 months, and 54 of them for 30 months, to study the relationship between fasting levels of immunoreactive C-peptide and titres of islet cell antibodies. After diagnosis, fasting C-peptide rose temporarily for 1–6 months of insulin therapy and declined continuously thereafter. While islet cell antibodies were present among 55% of the newly diagnosed patients, only 31% remained positive at 30 months. Their antibody titres decreased from 1∶81 at diagnosis to 1∶3. Only 3 patients (4%) who were islet cell antibody negative at diagnosis became positive later. The median C-peptide values among the persistently islet cell antibody positive patients decreased from 0.11 pmol/ml at 18 months, to 0.09 pmol/ml at 24 months, to 0.06 pmol/ml at 30 months compared to 0.18 (p=0.04), 0.15 (p=0.05) and 0.16 (p〈 0.003) pmol/ml, respectively, for the islet cell antibody negative patients. The median slope for the latter was −0.09 compared to −0.19 for the islet cell antibody positive patients (p=0.01). These differences were reflected in increasing dosages of insulin, since patients remaining antibody-positive for 30 months were given 1.3–1.4 times more insulin (p=0.01–0.004) than the antibody negative patients. This study demonstrates that islet cell antibodies may be a useful marker for predicting an increased rate by which endogenous B cell function is lost in Type 1 diabetes.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Incidence ; seasonal variation ; geographical pattern ; sex-difference ; epidemiology ; juvenile-onset ; insulin-dependent ; diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The incidence, sex, seasonal and geographical patterns of juvenile-onset insulin-dependent diabetes mellitus (j.i.d.m.) were studied retrospectively on one third of the Danish population 1970–1974. The j.i.d.m. incidence remained fairly constant during the study period, the average being 13.2 per 100000 per year. The total number of boys exceeded the number of girls by 27 per cent. A marked peak of incidence was found at 12–14 years, earlier for females than for males. A seasonal variation in onset (diagnosis) of j.i.d.m. was observed with the lowest number of new cases in May–July. The j.i.d.m. incidence seemed to show socioeconomic differences, being highest in those parts of the survey area with lower status.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Mouse ; experimental diabetes ; streptozotocin ; H-2 system ; sex hormone ; insulitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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 × 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 that major histocompatibility complex genes are not likely to determine susceptibility to streptozotocin-induced islet B cell damage.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Insulin-gene ; DNA-polymorphisms ; diabetes mellitus ; atherosclerosis ; genetic markers ; molecular genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A highly polymorphic locus flanking the human insulin gene contains two major size classes of DNA restriction fragments, which segregate in families as stable genetic elements. The L-allele, i.e. fragments with an average size of about 600 base-pairs seems to be a weak genetic marker for Type 1 (insulin-dependent) diabetes mellitus, whereas the Uallele, i. e. fragments of an average size of about 2500 basepairs hitherto has been associated with Type 2 (non-insulin-dependent) diabetes mellitus and diabetic hypertriglyceridaemia. The most recent reports on this subject do not confirm an association between the U-allele and Type 2 diabetes. Our own studies indicate that the U-allele is a fairly strong marker for the development of atherosclerosis (relative risk for U-carriers 3.36). The putative functions of the polymorphic region in atherogenesis and the relation of this region to other genetic markers for atherosclerosis are not known.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Experimental diabetes mellitus ; glucose intolerance ; virus ; autoimmunity ; immune response genes ; islet-cell-surface antibody ; major histocompatibility locus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: IDDM ; diabetic autonomic neuropathy ; prevalence ; simple bedside tests ; nerve function ; retinopathy ; nephropathy ; diabetic complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the prevalence of diabetic autonomic neuropathy, five simple bedside tests, beat-to-beat variation during quiet respiration, beatto-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 insulindependent 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 autonomic 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〈0.01) than patients without these complications.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: HLA ; genetics ; heterogeneity of insulin-dependent diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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-DR4 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.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 21 (1981), S. 549-553 
    ISSN: 1432-0428
    Keywords: Haemoglobin A1c ; synthesis ; glucose ; hyperglycaemia ; artificial pancreas ; density separated erythrocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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 HbA1c formation previously found in vitro. The stable HbA1c formed in 24 h was on average 0.006% of total haemoglobin/ mmol glucose. This compares well with the rate of HbA1c synthesis reported in normal subjects using 59Fe-kinetic measurements, and is in accordance with the concept of slow changes in stable HbA1c with time and glucose concentration. To investigate the possibility that the rate of HbA1c 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 HbA1c. Assuming the least dense cells to be the youngest erythrocytes, this observation is inconsistent with a slow linear increase in HbA1c. 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 HbA1c 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 HbA1c synthesis.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: DNA insertion sequences ; insulin gene ; maturityonset diabetes in young people
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The association between DNA insertion sequences located near the insulin gene and the dominantly inherited maturity-onset diabetes of young people was studied in a large family. The distribution of the restriction fragments was compatible with Mendelian segregation. However, no linkage was found between the DNA insertion sequences and this form of diabetes.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Type 2 diabetes ; HLA-Bw22 ; insulin gene ; Nauru ; Central Pacific ; diabetes genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Genetic factors play a major role in predisposition to diabetes in the Micronesian population of Nauru. In people aged 60 years and older, 83% of full-blooded Nauruans were diabetic compared with 17% of those with ancestral foreign admixture, as detected by HLA typing. HLA distributions also showed a small increased risk for early onset of diabetes (〈 46 years) associated with HLA-Bw22 (Bw56). Variation in the restriction fragment length of DNA near the insulin gene was found, but was not associated with diabetes. The distribution in fragment lengths, previously reported in Caucasoids, was observed in healthy Polynesians, Melanesians and Micronesians.
    Type of Medium: Electronic Resource
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