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  • 1
    Electronic Resource
    Electronic Resource
    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
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1992.tb03139.x
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  • 2
    Electronic Resource
    Electronic Resource
    Cytokine Expression in Unstimulated PBMC of Children with Type 1 Diabetes and Subjects Positive for Diabetes-Associated Autoantibodies (2001)
    Oxford, UK : Blackwell Science Ltd
    Scandinavian journal of immunology 53 (2001), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The aim of this study was to evaluate possible changes in the circulating levels of interferon (IFN)-γ, interleukin (IL)-4 and transforming growth factor (TGF)-β in association with the autoimmune process leading to type 1 diabetes. Expression levels of mRNAs specific for each cytokine were determined in peripheral blood mononuclear cells (PBMC) by a multiplex reverse transcription–polymerase chain reaction (RT–PCR) followed by hybridization reactions with lanthanide-labelled probes and detection by time-resolved fluorometry. Newly diagnosed diabetic children had lower levels of IFN-γ, IL-4 and TGF-β1 signals compared to their age- and sex-matched controls (P 〈 0.02, P 〈 0.005 and P 〈 0.005, respectively) and also the autoantibody-positive subjects had significantly lower levels of IL-4 and TGF-β1 in comparison with their matched controls (P = 0.0013 and P = 0.012). No significant differences were observed when comparing matched pairs of diabetic children and autoantibody-positive subjects. Our results suggest a systemic bias towards reduced production of T-helper cell type 2 cytokines (IL-4 and TGF-β1) during the autoimmune process, but there was also a reduced level of IFN-γ expression in the periphery at the onset of clinical diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.2001.00904.x
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  • 3
    Electronic Resource
    Electronic Resource
    Antibodies to GAD65 Epitopes at Diagnosis and Over the First 10 years of Clinical Type 1 Diabetes Mellitus (2004)
    Oxford, UK; Malden , USA : Blackwell Science Ltd
    Scandinavian journal of immunology 59 (2004), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Antibodies to glutamate decarboxylase (GAD65Ab) may persist, and their titres even increase after the clinical onset of type 1 diabetes. To characterize this phenomenon in detail, we analysed sequentially antibodies to GAD65 epitope clusters in a radio-binding assay in patients with type 1 diabetes. Serum samples were taken at diagnosis and 2, 5 and 10 years later from 50 young patients who had tested positive for GAD65Ab at least once during observation. The levels of GAD65Ab peaked in 21 patients after diagnosis. Antibodies to the middle region of GAD65 (GAD65-M-Ab, 88%) were more common at diagnosis than antibodies to the C-terminal (GAD65-C-Ab, 68%, P 〈 0.05) or N-terminal region (4%, P 〈 0.001). Antibodies to middle and especially to C-terminal epitopes decreased in those with decreasing levels of GAD65Ab (P 〈 0.001), whereas the frequencies of GAD65-M-Ab and GAD65-C-Ab remained quite stable among the subjects with increasing levels. Lower exogenous insulin dose and HbA1 levels and stronger humoral immune response to islet cells were observed in those with increasing levels of GAD65-M-Ab than in those with decreasing levels (P 〈 0.05). The present observation supports the view that the middle region of GAD65 comprises immunodominant epitopes. An enhanced humoral immune response to GAD65 after diagnosis is related to persistent immune reactivity to the middle and C-terminal regions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.0300-9475.2004.01402.x
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  • 4
    Electronic Resource
    Electronic Resource
    The occurrence of type 1 diabetes in patients with dermatitis herpetiformis and their first-degree relatives (2004)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 150 (2004), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  The increased prevalence of type 1 diabetes (T1D) is well documented in patients with coeliac disease, whereas evidence is scanty in patients with dermatitis herpetiformis (DH).Objectives  To assess the prevalence of T1D in patients with DH and their first-degree relatives, and to study how DH patients with associated T1D respond to a gluten-free diet (GFD) treatment.Methods  A series of 1104 consecutive patients with DH was recorded and a specific questionnaire sent to 341 of these for familial disease surveillance. Sex- and age-matched patients with isolated DH served as controls in the diet treatment analysis.Results  Twenty-five (2·3%) patients with DH were affected by T1D and three (3·0%) of their first-degree relatives also were affected by T1D, the frequencies being significantly higher than in the general population. Most DH patients with T1D and with isolated DH could adhere strictly to the GFD. The response was good or moderate in 84% of the DH patients with T1D and in 94% of the patients with isolated DH.Conclusions  The prevalence of T1D is increased in patients with DH and their first-degree relatives. The rash in DH patients with T1D responds to a GFD in a way similar to that seen in patients with isolated DH.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2004.05642.x
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  • 5
    Electronic Resource
    Electronic Resource
    Immunogenicity of monocomponent human and porcine insulin in newly diagnosed Type 1 (insulin-dependent) diabetic children (1984)
    Springer
    Diabetologia 27 (1984), S. 96-98 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 diabetes in children ; immunogenicity ; monocomponent human insulin ; monocomponent porcine insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of the present study was to compare the immunogenicity of monocomponent human insulin with that of monocomponent porcine insulin in newly diagnosed Type 1 (insulin-dependent) diabetic children. One hundred and thirty-five patients at diagnosis of diabetes (age 1–18 years, mean age 9.3 years) were randomly allocated to treatment with either Monotard MC + Actrapid MC or Monotard HM + Actrapid HM in a double-blind trial conducted in Sweden, Finland, Norway and Denmark. The human and porcine insulin groups were identical at diagnosis with respect to age, sex and measures of metabolic control. At all times the mean insulin antibody levels and the percentage of antibody-positive patients were lower in the human group compared with the porcine group. At 3 and 12 months, the insulin antibody values were significantly lower in the human group than in the porcine group (p 〈 0.05, Wilcoxon's rank sum test). At 12 months, antibody values in the human group ranged from 0 to 1.2 U/l (mean 0.14 U/l) and in the porcine insulin group from 0–5.2 U/l (mean 0.63 U/l). It is therefore concluded that human monocomponent insulin has a lower immunogenicity than porcine insulin of the same purity in newly diagnosed diabetic children during the first year of insulin treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00275658
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  • 6
    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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  • 7
    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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  • 8
    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
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  • 9
    Electronic Resource
    Electronic Resource
    Serological evaluation of the role of cytomegalovirus in the pathogenesis of IDDM: a prospective study (1995)
    Springer
    Diabetologia 38 (1995), S. 705-710 
    Details
    ISSN: 1432-0428
    Keywords: Key words Insulin-dependent diabetes mellitus ; cytomegalovirus ; pathogenesis ; prospective study ; ICA ; siblings.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To study the possible temporal association between primary cytomegalovirus infection and the appearance of islet cell autoantibodies or the development of insulin-dependent diabetes mellitus (IDDM) cytomegalovirus antibodies were analysed from follow-up sera of 46 initially non-diabetic siblings of diabetic children who either manifested clinical IDDM (22 siblings) or turned islet cell antibody positive (24 siblings) during the prospective observation (mean follow-up time 2.9 years). Secondly, cytomegalovirus antibodies were analysed during pregnancy in 96 mothers whose child presented with IDDM before the age of 7 years and in 96 control mothers who gave birth to a non-diabetic child. Thirdly, a case-control series including 90 newly-diagnosed young children with IDDM and their 90 control subjects was analysed. No seroconversions were found in cytomegalovirus antibodies during the follow-up of the 46 siblings indicating no temporal association with islet cell antibody seroconversion or manifestation of clinical diabetes. During the follow-up 17 (37 %) siblings were constantly seronegative and 29 (63 %) seropositive for cytomegalovirus IgG and there was no difference between islet cell antibody positive and negative siblings. Cytomegalovirus IgG and IgM were not different in pregnant mothers who gave birth to a subsequently diabetic child compared to control mothers, or in newly-diagnosed diabetic children compared to control children. Cytomegalovirus IgA was higher in newly-diagnosed diabetic children than in control children (p 〈 0.005). This difference disappeared when only cytomegalovirus IgG positive individuals were analysed. No correlation was found between islet cell antibodies and cytomegalovirus antibodies in newly-diagnosed diabetic patients. The results do not support the hypothesis that primary cytomegalovirus infections could initiate the cascade leading to autoimmune destruction of the beta cells. [Diabetologia (1995) 38: 705–710]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401843
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  • 10
    Electronic Resource
    Electronic Resource
    Prevention of IDDM: strategies based on new observations of molecular pathogenesis Workshop held in Majvik, Kirkkonummi, Finland, 6–8 May 1996 (1997)
    Springer
    Diabetologia 40 (1997), S. 743-748 
    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/s001250050744
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