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  • 1
    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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    Paper (German National Licenses)
    Fulltext
  • 2
    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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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    IA-2 antibodies – a sensitive marker of IDDM with clinical onset in childhood and adolescence (1998)
    Springer
    Diabetologia 41 (1998), S. 424-429 
    Details
    ISSN: 1432-0428
    Keywords: Keywords IA-2 antibodies ; GAD antibodies ; insulin autoantibodies ; islet cell antibodies ; HLA risk markers.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To study the relationship of IA-2 antibodies (IA-2A) to other autoantibodies and genetic risk markers in insulin-dependent diabetes mellitus (IDDM), 758 children and adolescents younger than 15 years of age (mean age 8.4 years) with newly diagnosed diabetes were analysed for IA-2A, GAD antibodies (GADA) and insulin autoantibodies (IAA) with radiobinding assays, for islet cell antibodies (ICA) with immunofluorescence and for HLA DR alleles by serology. IA-2A were detected in 85.9 % of cases with no association with gender or age. An overwhelming majority of the patients (71.3 %) tested positive for three or more antibodies, and 90.7 % for at least two. Fifty-four subjects (7.1 %) had one antibody detectable, whereas only 2.1 % of the patients tested negative for all four. A higher proportion of patients was positive for IA-2A and/or GADA than for ICA alone (95.5 vs 84.2 %, p 〈 0.001). The prevalence and level of IA-2A were increased in cases carrying HLA DR4/non-DR3 compared with other DR combinations. The results indicate that almost all patients with newly diagnosed childhood IDDM can be identified by screening with these four autoantibodies. The combination of IA-2A and/or GADA had a higher sensitivity for IDDM than ICA alone. The close association between IA-2A and HLA DR4, the strongest single allele predisposing to IDDM, suggests that IA-2A may be a more specific marker of beta-cell destruction than GADA, which have been shown to associate with the DR3 allele and thyroid autoimmunity. [Diabetologia (1998) 41: 424–429]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050925
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    The role of insulin in clustering of serum lipids and blood pressure in children and adolescents (1995)
    Springer
    Diabetologia 38 (1995), S. 1042-1050 
    Details
    ISSN: 1432-0428
    Keywords: Insulin ; longitudinal ; clustering ; children ; adolescents ; serum lipoproteins ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In adults hyperinsulinaemia is associated with an atherogenic risk profile including obesity, low levels of HDL-cholesterol, high levels of triglycerides and elevated blood pressure. To examine these associations in the young we studied the cross-sectional relationships of insulin with obesity indices (body mass index, subscapular skinfold thickness), serum lipids and blood pressure in 1,865 children, adolescents and young adults aged 6–24 years. We also used longitudinal data to study the value of a single insulin measurement to predict high risk factor levels and clustering of multiple risk factors after a 6-year follow-up. In cross-sectional analyses the levels of triglycerides, HDL-cholesterol, systolic blood pressure and obesity indices were usually significantly different across the quartiles of fasting insulin in both sexes among children, adolescents and young adults. In general, no associations were seen with total cholesterol or LDL-cholesterol. In prospective analysis elevated baseline insulin was related to the incidence of hypertriglyceridaemia (≥95th percentile) at the follow-up. This relationship persisted even after adjustments for baseline obesity or 6-year change in obesity status. Moreover, baseline insulin concentration was higher in subjects who subsequently showed clustering of high triglycerides, low HDL-cholesterol and high systolic blood pressure levels at the follow-up. We conclude that high fasting insulin levels measured in children and adolescents predict the development of hypertriglyceridaemia years later. In addition, high insulin levels seem to precede the development of a potentially atherogenic risk factor profile including low HDL-cholesterol, high triglycerides and high systolic blood pressure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402173
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    The role of insulin in clustering of serum lipids and blood pressure in children and adolescents The Cardiovascular Risk in Young Finns Study (1995)
    Springer
    Diabetologia 38 (1995), S. 1042-1050 
    Details
    ISSN: 1432-0428
    Keywords: Key words Insulin ; longitudinal ; clustering ; children ; adolescents ; serum lipoproteins ; blood pressure.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In adults hyperinsulinaemia is associated with an atherogenic risk profile including obesity, low levels of HDL-cholesterol, high levels of triglycerides and elevated blood pressure. To examine these associations in the young we studied the cross-sectional relationships of insulin with obesity indices (body mass index, subscapular skinfold thickness), serum lipids and blood pressure in 1,865 children, adolescents and young adults aged 6–24 years. We also used longitudinal data to study the value of a single insulin measurement to predict high risk factor levels and clustering of multiple risk factors after a 6-year follow-up. In cross-sectional analyses the levels of triglycerides, HDL-cholesterol, systolic blood pressure and obesity indices were usually significantly different across the quartiles of fasting insulin in both sexes among children, adolescents and young adults. In general, no associations were seen with total cholesterol or LDL-cholesterol. In prospective analysis elevated baseline insulin was related to the incidence of hypertriglyceridaemia (≥ 95th percentile) at the follow-up. This relationship persisted even after adjustments for baseline obesity or 6-year change in obesity status. Moreover, baseline insulin concentration was higher in subjects who subsequently showed clustering of high triglycerides, low HDL-cholesterol and high systolic blood pressure levels at the follow-up. We conclude that high fasting insulin levels measured in children and adolescents predict the development of hypertriglyceridaemia years later. In addition, high insulin levels seem to precede the development of a potentially atherogenic risk factor profile including low HDL-cholesterol, high triglycerides and high systolic blood pressure. [Diabetologia (1995) 38: 1042–1050]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402173
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 6
    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: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401843
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 7
    Electronic Resource
    Electronic Resource
    Costs of predicting IDDM (1998)
    Springer
    Diabetologia 41 (1998), S. 79-85 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin-dependent diabetes mellitus ; prediction ; prevention ; screening ; genetic risk ; islet cell antibodies ; autoimmunity ; costs.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Programmes aiming at prediction and prevention of insulin-dependent diabetes mellitus (IDDM), a multifactorial autoimmune disease, have been launched or are in the planning phase in several countries. We hypothesized that the costs of finding the correct target subjects for preventive interventions are likely to vary markedly according to the prediction strategy chosen. Average direct costs accruing in the Finnish IDDM Prediction and Prevention Project (DIPP) were analysed from the health care provider's viewpoint. The genetically targeted strategy included costs of assessing genetic IDDM susceptibility followed by measurement of marker(s) of islet autoimmunity in the susceptibility restricted population at 3 to 6-month intervals. In the pure immunological strategy markers of autoimmunity were repeatedly analysed in the entire population. The data were finally exposed to sensitivity analysis. The genetically targeted prediction strategy is cost-saving in the first year if autoimmune markers are analysed as frequently as under the DIPP project, and in all circumstances later. The 10-year direct costs per child are US$ 245 (present value $ 217, 5 % discount rate) if the genetically targeted approach is used and $ 733 (present value $ 619) if the pure immunological strategy is chosen. In sensitivity analysis the 10-year costs (present value) per child of the genetically targeted strategy and of the pure immunological strategy varied from $ 152 to $ 241 and from $ 430 to $ 788, respectively. The genetically targeted IDDM prediction strategy is remarkably cost-saving as compared with the pure immunological strategy mainly because fewer subjects will need retesting during the follow-up. [Diabetologia (1998) 41: 79–85]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050870
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    Paper (German National Licenses)
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  • 8
    Electronic Resource
    Electronic Resource
    Autoantibodies associated with Type I diabetes mellitus persist after diagnosis in children (1998)
    Springer
    Diabetologia 41 (1998), S. 1293-1297 
    Details
    ISSN: 1432-0428
    Keywords: Keywords IA-2 antibodies ; GAD antibodies ; islet cell antibodies ; insulin autoantibodies ; clinical characteristics ; HLA risk markers.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To study the persistence of Type I (insulin-dependent) diabetes mellitus associated autoantibodies and their relation to genetic risk markers and clinical characteristics of the disease after clinical manifestation, serum samples were obtained from 90 children and adolescents at diagnosis and 2, 5 and 10 years later. The samples were analysed for islet cell antibodies (ICA) by immunofluorescence and for antibodies to glutamic acid decarboxylase (GADA), intracellular portion of the protein tyrosine phosphatase related IA-2 antigen (IA-2A) and insulin autoantibodies by specific radiobinding assays. Of the subjects tested 79 % were positive for IA-2A at diagnosis, 62 % for GADA, 81 % for ICA and 28 % for insulin autoantibodies, but the prevalence of IA-2A, GADA and ICA decreased substantially as a function of increasing duration of the disease (p 〈 0.05 or less), their levels following the same pattern (p 〈 0.001 for all three autoantibodies). Two thirds of the subjects still tested positive for at least one autoantibody specificity after the first 10 years of the disease and 42 % had two or three antibodies detectable. An increase over the initial antibody concentrations after the diagnosis was seen more often for GADA than for ICA (p 〈 0.001) or IA-2A (p 〈 0.05). In conclusion, autoantibodies associated with Type I diabetes appear to persist longer than expected after manifestation of the clinical disease, possibly due to small scale continuous beta-cell regeneration after diagnosis or to structural and/or functional mimicry between exogenous proteins and beta-cell antigens or both. [Diabetologia (1998) 41: 1293–1297]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051067
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    Paper (German National Licenses)
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  • 9
    Electronic Resource
    Electronic Resource
    Prepubertal girls with insulin-dependent diabetes mellitus have higher exogenous insulin requirement than boys (1998)
    Springer
    European journal of pediatrics 157 (1998), S. 708-711 
    Details
    ISSN: 1432-1076
    Keywords: Key words Insulin dose ; Insulin sensitivity ; Gender ; Type 1 diabetes ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a population based study, the prescribed insulin dose of 348 prepubertal children with insulin-dependent diabetes mellitus (IDDM) was analysed 2 years after the diagnosis of diabetes. Girls had an insulin dose 13.6% higher than that in boys. When children younger than 5 years of age at diagnosis were analysed separately, the difference in insulin dose between boys and girls remained. The increased insulin dose in girls was not explained by possible differences in endogenous insulin secretion, body mass index, metabolic control or the number of daily insulin injections. Our observations indicate that prepubertal girls with IDDM have a poorer insulin sensitivity than boys.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310050919
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    Paper (German National Licenses)
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