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  • 1
    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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  • 2
    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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  • 3
    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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  • 4
    Electronic Resource
    Electronic Resource
    A model for the involvement of MHC class II proteins in the development of Type 1 (insulin-dependent) diabetes mellitus in response to bovine serum albumin peptides (1993)
    Springer
    Diabetologia 36 (1993), S. 364-368 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Conclusions Considerations of the structure of a candidate initiating antigen have led us to propose a new model for the susceptibility to Type 1 diabetes. It is quite likely there are other antigens of similar structure of viral or bacterial origin that will provoke a similar response directed against islet beta cells. However, we believe that this hypothesis will provide a framework for the further investigation and research into the mechanism of development of Type 1 diabetes and for the design of therapeutic manoeuvres for its prevention.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400243
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  • 5
    Electronic Resource
    Electronic Resource
    Diet, cow's milk protein antibodies and the risk of IDDM in Finnish children (1994)
    Springer
    Diabetologia 37 (1994), S. 381-387 
    Details
    ISSN: 1432-0428
    Keywords: Infant feeding ; dairy products ; cow's milk protein antibodies ; IDDM ; childhood ; islet cell antibodies ; insulin autoantibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Associations of infant feeding patterns and milk consumption with cow's milk protein antibody titres were studied in 697 newly-diagnosed diabetic children, 415 sibling-control children and 86 birth-date-and sex-matched population-based control children in the nationwide “Childhood Diabetes in Finland” study. IgA and IgG antibody titres to the proteins of cow's milk formula, BLG and BSA, and IgM antibody titres to cow's milk formula proteins were measured by ELISA. Several inverse correlations were observed between the duration of breast-feeding or age at introduction of dairy products and antibody titres, and positive correlations were observed between milk consumption and antibody titres in all three populations studied. Multivariate analyses which included the infant feeding variables, milk consumption and current age simultaneously showed that the earlier the introduction of dairy products and the greater the consumption of milk was, the higher several antibody titres were. High IgA antibody titres to cow's milk formula were associated with a greater risk of IDDM both among diabeticpopulation-control and diabetic-sibling-control pairs when adjusted for other cow's milk antibody titres, dietary variables and in diabetic-sibling-control pairs also for ICA. The results suggest that young age at introduction of dairy products and high milk consumption during childhood increase the levels of cow's milk antibodies and that high IgA antibodies to cow's milk formula are independently associated with increased risk of IDDM.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00408475
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  • 6
    Electronic Resource
    Electronic Resource
    Natural history of preclinical IDDM in high risk siblings (1994)
    Springer
    Diabetologia 37 (1994), S. 388-393 
    Details
    ISSN: 1432-0428
    Keywords: Preclinical IDDM ; islet cell antibodies ; early insulin response ; glucose elimination rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To learn more about the preclinical phase of IDDM we observed for a median period of 46.5 months (range 0.5–69 months) a group of 57 siblings positive for ICA and/or IAA when first screened within 6 months of the diagnosis of the proband. Sequential blood samples and IVGTTs were obtained at intervals of 6–12 months. Seventeen siblings (29.8%) presented with IDDM during the observation period. The duration of the known preclinical period ranged from 0.5 to 51 months (median 29 months). The converters were younger than the other siblings (P〈0.05) and had higher initial ICA levels (P〈0.01). In addition they had a lower FPIR in the first IVGTT (P〈0.001). On all subsequent tests the converters had higher ICA levels and a lower FPIR (P〈0.05 or less), a lower glucose elimination rate from the third test onwards (P〈0.01 or less) and higher IAA levels at 3 years (P〈0.05). Some variation could be observed in the FPIR in the converters with an initial increase and subsequent decrease (P〈0.05 for both). Their levels of complement-fixing ICA increased up to 18 months (P〈0.05) and IAA levels up to 3 years (P〈0.01). Those high risk siblings who progress to clinical IDDM are characterized by young age, strong and increasing signs of islet-cell specific autoimmunity, reduced insulin secreting capacity and emerging glucose intolerance. The present observations seem to be incompatible with the hypothesis of beta-cell destruction occurring at a constant, predictable rate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00408476
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  • 7
    Electronic Resource
    Electronic Resource
    Increasing trend in Type 1 (insulin-dependent) diabetes mellitus in childhood in Finland (1991)
    Springer
    Diabetologia 34 (1991), S. 282-287 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; incidence ; epidemiology ; time trends ; Finland
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The Central Drug Registry in Finland ascertained 5,920 incident cases of Type 1 (insulin-dependent) diabetes mellitus diagnosed under the age of 15 years, during 1965–1984. The incidence was higher for males 29.2/100,000 (95% confidence intervals 28.2–30.2/100,000) than for females 26.1/100,000 (25.1–27.1/100,000). A non-linear increase in incidence with age was confirmed, with peaks at ages 2,9 and 14 years in males and at 3,5–6 and 11 years in females. A significant temporal variation in incidence was found, adjusting for age and sex. During 1965 to 1984 the incidence rose by about 57% or by 2.4% annually. However, a non-linear curve with two incidence peaks in 1978 and 1983 would better describe the temporal pattern than a linear trend. There was no significant difference in the temporal variation between males and females. The changes in diabetes risk appeared to affect proportionally all age groups under 15 years. Two possible mechanisms were explored: a calendar period effect vs a birth cohort effect. The calendar time period effect was significant alone and also when adjusted for the birth cohort effect. One the contrary, the birth cohort effect was not significant, when adjusted for the calendar period effect. In conclusion, over the past two decades, the incidence of childhood Type 1 diabetes in Finland has increased by about 57%. The pattern of change was a steady rising background incidence superimposed by sudden outbreaks suggesting environmental causative factors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00405089
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  • 8
    Electronic Resource
    Electronic Resource
    Fourth International Onnela Workshop Immunology and Diet — Towards the Prevention of Type 1 (insulin-dependent) Diabetes? (1990)
    Springer
    Diabetologia 33 (1990), S. 509-510 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00405115
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    Paper (German National Licenses)
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  • 9
    Electronic Resource
    Electronic Resource
    Natural history of preclinical IDDM in high risk siblings (1994)
    Springer
    Diabetologia 37 (1994), S. 388-393 
    Details
    ISSN: 1432-0428
    Keywords: Key words Preclinical IDDM, islet cell antibodies, early insulin response, glucose elimination rate.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To learn more about the preclinical phase of IDDM we observed for a median period of 46.5 months (range 0.5–69 months) a group of 57 siblings positive for ICA and/or IAA when first screened within 6 months of the diagnosis of the proband. Sequential blood samples and IVGTTs were obtained at intervals of 6–12 months. Seventeen siblings (29.8 %) presented with IDDM during the observation period. The duration of the known preclinical period ranged from 0.5 to 51 months (median 29 months). The converters were younger than the other siblings (P〈0.05) and had higher initial ICA levels (P〈0.01). In addition they had a lower FPIR in the first IVGTT (P〈0 .001). On all subsequent tests the converters had higher ICA levels and a lower FPIR (P〈0.05 or less), a lower glucose elimination rate from the third test onwards (P〈0.01 or less) and higher IAA levels at 3 years (P〈0.05). Some variation could be observed in the FPIR in the converters with an initial increase and subsequent decrease (P〈0.05 for both). Their levels of complement-fixing ICA increased up to 18 months (P〈0.05) and IAA levels up to 3 years (P〈0.01). Those high risk siblings who progress to clinical IDDM are characterized by young age, strong and increasing signs of islet-cell specific autoimmunity, reduced insulin secreting capacity and emerging glucose intolerance. The present observations seem to be incompatible with the hypothesis of beta-cell destruction occurring at a constant, predictable rate. [Diabetologia (1994) 37: 388-393]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00408476
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 10
    Electronic Resource
    Electronic Resource
    Diet, cow's milk protein antibodies and the risk of IDDM in Finnish children (1994)
    Springer
    Diabetologia 37 (1994), S. 381-387 
    Details
    ISSN: 1432-0428
    Keywords: Key words Infant feeding, dairy products, cow's milk protein antibodies, IDDM, childhood, islet cell antibodies, insulin autoantibodies.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Associations of infant feeding patterns and milk consumption with cow's milk protein antibody titres were studied in 697 newly-diagnosed diabetic children, 415 sibling-control children and 86 birth-date- and sex-matched population-based control children in the nationwide “Childhood Diabetes in Finland” study. IgA and IgG antibody titres to the proteins of cow's milk formula, BLG and BSA, and IgM antibody titres to cow's milk formula proteins were measured by ELISA. Several inverse correlations were observed between the duration of breast-feeding or age at introduction of dairy products and antibody titres, and positive correlations were observed between milk consumption and antibody titres in all three populations studied. Multivariate analyses which included the infant feeding variables, milk consumption and current age simultaneously showed that the earlier the introduction of dairy products and the greater the consumption of milk was, the higher several antibody titres were. High IgA antibody titres to cow's milk formula were associated with a greater risk of IDDM both among diabetic-population-control and diabetic-sibling-control pairs when adjusted for other cow's milk antibody titres, dietary variables and in diabetic-sibling-control pairs also for ICA. The results suggest that young age at introduction of dairy products and high milk consumption during childhood increase the levels of cow's milk antibodies and that high IgA antibodies to cow's milk formula are independently associated with increased risk of IDDM. [Diabetologia (1994) 37: 381–387]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00408475
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
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