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  • 1
    Electronic Resource
    Electronic Resource
    An analysis of epidemiological data in HLA-typed diabetic children (1985)
    Springer
    Diabetologia 28 (1985), S. 397-400 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; HLA ; seasonal variation ; age at diagnosis ; sex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To clarify the heterogeneity of Type 1 (insulin-dependent) diabetes mellitus, differences between patients with different HLA risk antigens were investigated with regard to sex, age at diagnosis, season of year and calendar year at diagnosis of the disease. The study consisted of 293 HLA-typed patients from the Department of Paediatrics, University of Oulu, Oulu, Finland. HLA-Dw2 was extremely rare among diabetic patients, whereas Dw3 and Dw4 were associated with increased risk in this as in other series. Male patients more often had the HLA-A1 antigen than females. On comparison of the Dw3 positive patients, boys more frequently had the combination A1,B8 than girls. A1,B8-positive patients were more often diagnosed during the warm months, in the late summer and autumn. Patients with both Dw3 and Dw4 were younger at diagnosis when compared with the rest of the patients. The results support the concept of heterogeneity in the pathogenesis of Type 1 diabetes associated with HLA-linked genetic determinants.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280881
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  • 2
    Electronic Resource
    Electronic Resource
    Accumulation of lipid in muscular arteries of short-term diabetic rats (1980)
    Springer
    Diabetologia 19 (1980), S. 529-534 
    Details
    ISSN: 1432-0428
    Keywords: Diabetes ; streptozotocin ; coronaryartery ; muscular pulmonary artery ; tibial artery ; aorta ; main pulmonary artery ; elastic arteries ; plasmanon-esterified fatty acid (NEFA)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Lipid accumulation in muscular (pulmonary, coronary and tibial) arteries and elastic (aorta and pulmonary) arteries of streptozotocin diabetic (65 mg/kg) rats was studied with an electron microscope. Arterial tissue specimens taken 4 days after the induction of diabetes showed lipid deposits in smooth muscle cells in the muscular arteries of 9 out of 24 diabetic rats, but in none of the 17 control rats. Histochemically the lipid was identified as triacylglycerol. Lipid accumulation was not seen in the elastic arteries of either diabetic or control rats. The diabetic animals with lipid deposits had slightly but significantly higher plasma glucose concentrations (p〈0.02), higher non-esterified fatty acids levels (p〈0.01), and lower concentrations of plasma insulin (p〈0.02) than those without arterial deposits. The amount of lipid deposited in the arteries was closely related to the plasma non-esterified fatty acid level, which was in the ranges 0.8–1.1 mmol/l in diabetic rats without deposits, and 1.1–2.4 mmol/l in those with deposits. The findings suggest that lipid accumulation in smooth muscle cells of muscular arteries during acute diabetes could result from the high plasma non-esterified fatty acid concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00253180
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    The influence of insulin on the lipids in the pulmonary artery and the lungs of severely diabetic rats (1979)
    Springer
    Diabetologia 16 (1979), S. 59-64 
    Details
    ISSN: 1432-0428
    Keywords: Diabetes ; insulin ; non-esterified fatty acids ; lipid metabolism ; lung ; phospholipids ; pulmonary artery ; rat ; streptozotocin ; triglycerides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of insulin on the triglyceride deposits found in the pulmonary artery branches of streptozotocin-diabetic rats was investigated by treating the animals for two, five, nine or 14 days with insulin (3–8 units/day). Histochemical analysis showed that the triglyceride deposits in the pulmonary artery developed within three to four days after the induction of diabetes, but were not present in any animals five days from the initiation of insulin therapy. Plasma triglycerides, non-esterified fatty acids, phospholipid and total cholesterol concentrations were within the normal range within two days of the inception of insulin therapy and random plasma glucose levels were normal within five days. Analysis of lung lipids showed that after 14 days of insulin treatment the decreased content of phospholipids and the increased content of non-esterified fatty acids found in diabetic rats were also normalized. These findings suggest that insulin has an important role in the regulation of lipid metabolism in the pulmonary artery and lung tissue in the diabetic state.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00423152
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  • 4
    Electronic Resource
    Electronic Resource
    Lipids in the pulmonary artery and the lungs of severely diabetic rats (1977)
    Springer
    Diabetologia 13 (1977), S. 305-310 
    Details
    ISSN: 1432-0428
    Keywords: Diabetes ; non-esterified fatty acids ; lipid metabolism ; lung ; phospholipids ; pulmonary artery ; rat ; streptozotocin ; triglycerides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the effect of diabetes on the lipid composition of the lungs and of the pulmonary artery, 43 streptozotocin diabetic rats and 43 control rats were examined. Triglyceride deposits were observed by a histochemical method in the branches of the pulmonary artery in 10 diabetic rats but in none of the controls. In the pulmonary tissue of the diabetic rats the total lipid content was not different from that of control animals, but the relative amount of phospholipids was decreased (p〈0.001), and that of non-esterified fatty acids (p〈0.001) and triglycerides (p〈0.05) increased as compared to the control rats. These results indicate abnormalities in the lipid metabolism of the pulmonary artery and lungs during insulin deficiency.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01223270
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  • 5
    Electronic Resource
    Electronic Resource
    Influence of norepinephrine and exercise on lipolysis in adipose tissue of diabetic rats (1975)
    Springer
    Diabetologia 11 (1975), S. 401-405 
    Details
    ISSN: 1432-0428
    Keywords: Adipose tissue ; catecholamines ; diabetes ; exercise ; free fatty acids ; glycerol ; lipolysis ; rat ; streptozotocin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The lipolytic effect of norepinephrine (NE) in adipose tissue in vitro was studied before and after exercise in non-fasted rats with severe, untreated streptozotocin diabetes. It was observed that: 1. NE in increasing concentrations stimulated glycerol release in vitro to an equal extent from the adipose tissue of nondiabetic and diabetic rats. However, the re-esterification of free fatty acids (FFA) in adipose tissue in vitro was decreased by NE in diabetic rats as compared to normal rats. 2. During exercise NE further decreased the re-esterification of FFA in vitro in adipose tissue of diabetic rats. 3. Exercise did not change NE-induced glycerol release in vitro in the adipose tissue of diabetic rats. 4. In diabetic animals the increase in plasma glycerol and FFA during exercise was correlated inversely with the NE-induced release of glycerol and FFA from the adipose tissue of the same animals after exercise. The lipolytic effect of NE is not significantly different in adipose tissue of diabetic and nondiabetic rats. By decreasing the re-esterification of FFA in vitro, NE is probably responsible for the observed increase in the release of FFA in vivo, a likely energy source in severely diabetic animals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00429907
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  • 6
    Electronic Resource
    Electronic Resource
    Lymphocyte subpopulations at the onset of type 1 (insulin-dependent) diabetes (1984)
    Springer
    Diabetologia 27 (1984), S. 106-108 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; T-lymphocytes ; heterogeneity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Percentages of various T-lymphocyte subpopulations in the blood were studied at the onset of Type 1 (insulin-dependent) diabetes. The number of lymphocytes with OKT8 markers was higher in the diabetic patients than in control subjects (p〈 0.005) and the ratio between helper and suppressor/cytotoxic T-cells (OKT4/OKT8 ratio) was lower in the diabetic patients than in the control group (p〈 0.005). The values in the diabetic patients were, however, essentially within the normal range. When Ia-antigen-positive cells were analysed in T-cell-enriched cell populations, Type 1 diabetic patients had higher percentages of these cells (p〈 0.01), suggesting T-cell activation. When patients with either of the two major HLA risk antigens (Dw3 or Dw4) were compared, there was a significant difference in the OKT4/OKT8 ratio (p〈 0.005), as Dw3-positive patients had higher and Dw4-positive patients lower ratios. This finding supports the concept of heterogeneity of the disease and can also explain the discrepant findings of earlier studies. When patients with complement-fixing islet cell antibodies were compared with patients without islet cell antibodies, there was no significant difference, although the OKT4/OKT8 ratio was slightly lower in the complement-fixing islet cell antibody-positive patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00275661
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  • 7
    Electronic Resource
    Electronic Resource
    A ‘new’ DR4 associated D specificity ‘JA’ in Type 1 (insulin-dependent) diabetes: A9, Bw16, DJA, DR4 haplotype (1984)
    Springer
    Diabetologia 27 (1984), S. 126-128 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; children ; HLA ; DR4 associated ; specificity (‘JA’)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The HLA antigen combination A9, Bw16 has been found to be associated with Type 1 (insulin-dependent) diabetes characterized by some special features in Northern Finland. This antigen combination has now been associated with a ‘new’ DR4-associated D antigen, provisionally called ‘JA’ or ‘SN’. This ‘new’ D specificity was also associated with HLA-B18. Although the combination, Dw3/DJA, was common in Type 1 diabetic patients, the frequency of the combination Dw4/DJA was decreased compared with the expected value. This supports the hypothesis of two different risk factors associated with DR3 and DR4.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00275668
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  • 8
    Electronic Resource
    Electronic Resource
    HLA haplotypes in Type 1 (insulin-dependent) diabetes mellitus: molecular analysis of the HLA-DQ locus (1992)
    Springer
    Diabetologia 35 (1992), S. 254-260 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; HLA haplotypes ; HLA-DQ ; restriction fragment length polymorphism ; genetics ; disease susceptibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In Caucasians the predisposition to Type 1 (insulin-dependent) diabetes mellitus has been shown to associate with HLA-DR3,DQw2 and DR4,DQw8 and with the presence of amino acids other than aspartic acid at position 57 on the HLA-DQβ chain. In Finland the haplotype-specific absolute risk for developing Type 1 diabetes differs between various DR3 and DR4 positive haplotypes. The aim of our present analysis was to find out whether this variation is attributable to polymorphism at the DQ locus. As part of a nationwide prospective study including 757 serologically HLA genotyped families, we determined HLA-DQα and DQβ restriction fragment polymorphisms in 17 selected families with important susceptibility haplotypes. Additionally, the DQA1 alleles were determined from 19 haplotypes using sequence-specific oligonucleotide probes, and the DQB1 second exon was sequenced from nine haplotypes. The DR3 as well as DR4 positive haplotypes frequently found in Type 1 diabetic patients showed no variation at the HLA-DQ locus, and they were DQw2 and DQw8, respectively. The absolute risk for Type 1 diabetes for DR4,DQw8 positive haplotypes A2,Cw4,Bw35,DR4 A3,Cw3,Bw62,DR4, A24,Cw7,Bw39,DR4, A2,Cw3,Bw62, DR4, and A2,Cw1,Bw56,DR4 was 35/100,000, 130/100,000, 166/100,000, 196/100,000, and 218/100,000, respectively. The absolute risks for DR3,DQw2 positive haplotypes A1, Cw7,B8,DR3 and A2,Cw7,B8,DR3 were 68/100,000 and 103/100,000, respectively. These results provide further evidence that not only the polymorphism at the DQ locus but also other genes of the haplotypes contribute to susceptibility to Type 1 diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400926
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  • 9
    Electronic Resource
    Electronic Resource
    Epidemiology of childhood diabetes mellitus in Finland — background of a nationwide study of Type 1 (insulin-dependent) diabetes mellitus (1992)
    Springer
    Diabetologia 35 (1992), S. 70-76 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; epidemiology ; genetic-environmental interaction ; incidence ; familial occurrence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A nationwide study of childhood Type 1 (insulin-dependent) diabetes mellitus was established in 1986 in Finland, the country with the highest incidence of this disease worldwide. The aim of the project called “Childhood Diabetes in Finland” is to evaluate the role of genetic, environmental and immunological factors and particularly the interaction between genetic and environmental factors in the development of Type 1 diabetes. From September 1986 to April 1989, 801 families with a newly-diagnosed child aged 14 years or younger at the time of diagnosis were invited to participate in this study. The vast majority of the families agreed to participate in the comprehensive investigations of the study. HLA genotypes and haplotypes were determined in 757 families (95%). Our study also incorporates a prospective family study among non-diabetic siblings aged 3–19 years, and two case-control studies among the youngonset cases of Type 1 diabetes. During 1987–1989, the overall incidence of Type 1 diabetes was about 35.2 per 100,000 per year. It was higher in boys (38.4) than in girls (32.2). There was no clear geographic variation in incidence among the 12 provinces of Finland. Of the 1,014 cases during these 3 years only six cases were diagnosed before their first birthday. The incidence was high already in the age group 1–4-years old: 33.2 in boys and 29.5 in girls. Of the 801 families 90 (11.2%) were multiple case families, of which 66 had a parent with Type 1 diabetes at the time of diagnosis of the proband. The prevalence of Type 1 diabetes in the parents of these newly-diagnosed diabetic children was higher in fathers (5.7%) than in mothers (2.6%).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400854
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  • 10
    Electronic Resource
    Electronic Resource
    Decline of mumps antibodies in Type 1 (insulin-dependent) diabetic children and a plateau in the rising incidence of Type 1 diabetes after introduction of the mumps-measles-rubella vaccine in Finland (1993)
    Springer
    Diabetologia 36 (1993), S. 1303-1308 
    Details
    ISSN: 1432-0428
    Keywords: Mumps ; mumps antibodies ; mumps-measlesrubella vaccination ; Type 1 (insulin-dependent) diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A nationwide mumps-measles-rubella vaccination was introduced in 1982 in Finland to children aged 1.5 to 6 years and since then mumps has virtually disappeared in the country. We investigated whether this rapid epidemiological change had any impact on antibody activity against mumps virus in Type 1 (insulin-dependent) diabetic children or on the incidence of Type 1 diabetes in Finland. Two case-control series were collected before (series I and II) and three series after (series III–V) the introduction of the vaccination. IgA class mumps antibody levels were significantly higher in Type 1 diabetic children than in matched control children in the first two but not in the three later series. IgG class antibody levels were similar in patients and control subjects in the first two series but significantly lower in patients than in control subjects in the three later series. The overall incidence of Type 1 diabetes in 0–14-year-old children increased until 1987 but remained about the same during 1988–1990. In 5–9-year-old children no further increase in Type 1 diabetes was seen since 1985, whereas in 0–4-year-old children the incidence continued to rise until 1990. The results suggest that the elimination of natural mumps by mumps-measles-rubella vaccination may have decreased the risk for Type 1 diabetes in Finland; a possible causal relationship is substantiated by the observed concomitant decrease in mumps antibody levels in diabetic children. However, further studies are required to determine if the vaccine virus, like natural mumps, could trigger the clinical onset of Type 1 diabetes in young children.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400810
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