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  • 1
    Digitale Medien
    Digitale Medien
    Tumour Necrosis Factor-β Gene RFLP Alleles in Finnish IDDM Hapiotypes (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 36 (1992), S. 0 
    Details
    ISSN: 1365-3083
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: The genes located between class II and class I HLA genes including polymorphic tumour necrosis factor (TNF) genes may contribute to the disease susceptibility in IDDM. Restriction fragment polymorphisms of the TNF-β gene have been found to be fixed in the major IDDM susceptibility haplotypes, the B62,DR4 haplotype being associated with the 10.5-kb fragment and the B8,DR3 haplotype with a 5.5-kb fragment. We studied this TNF polymorphism in a sample of diabetic families. In all IDDM-associated haplotypes (n= 129) the 5.5-kb allele was more frequent than in haplotypes found only in healthy family members (n=112) (58.1% versus 40.2%, P〈0.01). Among IDDM haplotypes the B62,DR4 haplotype was characterized by the 10.5-kb TNF fragment, whereas two other common Finnish IDDM-associated DR4 haplotypes-A24,B39,DR4 and A2,B56,DR4-had the 5.5-kb TNF fragment. Both IDDM-associated and non-associated DR3 positive haplotypes were linked to the 5.5-kb fragment. The distribution of various combinations of TNF alleles in IDDM probands (n= 63) did not differ from that expected according to the Hardy-Weinberg distribution. Our results indicate that the 10.5-kb allele of TNF-β gene as such is not a risk factor contributing to DR4/DQ8-associated susceptibility. Alternatively, there may be heterogeneity in pathogenetic effector mechanisms.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1365-3083.1992.tb03139.x
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  • 2
    Digitale Medien
    Digitale Medien
    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
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00405115
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  • 3
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Type 1 diabetes ; incidence ; epidemiology ; time trends ; Finland
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00405089
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  • 4
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Mumps ; mumps antibodies ; mumps-measlesrubella vaccination ; Type 1 (insulin-dependent) diabetes mellitus
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00400810
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  • 5
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Infant feeding ; dairy products ; cow's milk protein antibodies ; IDDM ; childhood ; islet cell antibodies ; insulin autoantibodies
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00408475
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  • 6
    Digitale Medien
    Digitale Medien
    Natural history of preclinical IDDM in high risk siblings (1994)
    Springer
    Diabetologia 37 (1994), S. 388-393 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Preclinical IDDM ; islet cell antibodies ; early insulin response ; glucose elimination rate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00408476
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  • 7
    Digitale Medien
    Digitale Medien
    Natural history of preclinical IDDM in high risk siblings (1994)
    Springer
    Diabetologia 37 (1994), S. 388-393 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Key words Preclinical IDDM, islet cell antibodies, early insulin response, glucose elimination rate.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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]
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00408476
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  • 8
    Digitale Medien
    Digitale Medien
    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
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00400243
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  • 9
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Key words Infant feeding, dairy products, cow's milk protein antibodies, IDDM, childhood, islet cell antibodies, insulin autoantibodies.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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]
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00408475
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  • 10
    Digitale Medien
    Digitale Medien
    HLA-DQ beta-chain restriction fragment length polymorphism as a risk marker in Type 1 (insulin-dependent) diabetes mellitus: a Finnish family study (1990)
    Springer
    Diabetologia 33 (1990), S. 357-362 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Type 1 (insulin-dependent) diabetes ; restriction fragment length polymorphism ; HLA-DQ ; prediction of Type 1 diabetes ; genetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Finnish Type 1 (insulin-dependent) diabetic families were analysed for HLA-DQ beta-chain polymorphism using a short intron-specific probe. A simple hybridization pattern was obtained in which all fragments were associated significantly with Type 1 diabetes. The simultaneous presence of two different risk markers, the allelic 12-kilobase and 4-kilobase fragments were strongly associated with Type 1 diabetes since 50% of the patients had this combination compared with only 2% of the control subjects. The cosegregated 7.5/3.0 kilobase fragments, which were associated with HLA-DR2 and DRw6 were not detected among the diabetic patients but were present in 48% of the control subjects. Our results provide further support for the location of susceptibility determining factors in the HLA-DQ gene area. The clear-cut, simple restriction fragment length polymorphism pattern obtained here, which bears a resemblance to a two allelic system, therefore makes this method applicable for estimating the risk of Type 1 diabetes at the population level.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00404640
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