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  • HLA-DQ  (3)
  • Diabetes mellitus  (2)
  • islet cell antibodies  (2)
  • 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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    Paper (German National Licenses)
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  • 2
    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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  • 3
    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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  • 4
    Electronic Resource
    Electronic Resource
    Concordance for Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus in a population-based cohort of twins in Finland (1992)
    Springer
    Diabetologia 35 (1992), S. 1060-1067 
    Details
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; twins ; prevalence ; concordance ; heritability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied the cumulative incidence, concordance rate and heritability for diabetes mellitus in a nationwide cohort of 13,888 Finnish twin pairs of the same sex. The twins were born before 1958 and both co-twins were alive in 1967. Data on diabetes were derived through computerized record linkage from death certificates, the National Hospital Discharge Register and the National Drug Register. Records were reviewed in order to assign a diagnostic category to the 738 diabetic patients identified. Of these patients 109 had Type 1 (insulin-dependent) diabetes, 505 Type 2 (non-insulin-dependent) diabetes, 46 gestational diabetes, 24 secondary diabetes, 38 impaired glucose tolerance and 16 remained unclassified. The cumulative incidence of diabetes was 1.4 % in men and 1.3 % in women aged 28–59 years and 9.3 % and 7.0 % in men and women aged 60 years and over, respectively. The cumulative incidence did not differ between monozygotic and dizygotic twins. The concordance rate for Type 1 diabetes was higher among monozygotic (23 % probandwise and 13 % pairwise) than dizygotic twins (5 % probandwise and 3 % pairwise). The probandwise and pairwise concordance rates for Type 2 diabetes were 34% and 20% among monozygotic tiwns and 16% and 9 % in dizygotic twins, respectively. Heritability for Type 1 diabetes was greater than that for Type 2 where both genetic and environmental effects seemed to play a significant role.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02221682
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  • 5
    Electronic Resource
    Electronic Resource
    Diabetes mellitus, impaired glucose tolerance and mortality among elderly men: The Finnish cohorts of the seven countries study (1992)
    Springer
    Diabetologia 35 (1992), S. 760-765 
    Details
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; elderly ; mortality ; cardiovascular disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied the association of glucose intolerance with total and cause-specific mortality during a 5-year follow-up of 637 elderly Finnish men aged 65 to 84 years. Total mortality was 276 per 1000 for men aged 65 to 74 years and 537 per 1000 for men aged 75 to 84 years. Five-year total mortality adjusted for age was 364 per 1000 in diabetic men, 234 per 1000 in men with impaired glucose tolerance and 209 per 1000 in men with normal glucose tolerance. The relative risk of death among diabetic men was 2.10 (95% confidence interval 1.26 to 3.49) and among men with impaired glucose tolerance 1.17 (95% confidence interval 0.71 to 1.94) times higher compared with men with normal glucose tolerance. Cardiovascular disease was the most common cause of death in every glucose tolerance group. The multivariate adjusted relative risk of cardiovascular death was increased (1.55) in diabetic patients, albeit non-significantly (95% confidence interval 0.84 to 2.85). Diabetes resulted in an increased risk of cardiovascular mortality among men aged 65–74 years but not among the 75–84-year-old men. Relative risk of death from non-cardiovascular causes was slightly increased among diabetic subjects. In conclusion, diabetes mellitus is a significant determinant of mortality among elderly Finnish men.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00429097
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  • 6
    Electronic Resource
    Electronic Resource
    A gene in the HLA class I region contributes to susceptibility to IDDM in the Finnish population (1994)
    Springer
    Diabetologia 37 (1994), S. 937-944 
    Details
    ISSN: 1432-0428
    Keywords: Genetics ; haplotype ; HLA-A ; HLA-DQ ; HLA-DR ; tumour necrosis factor ; diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In Finland the haplotype A2, Cw1, B56, DR4, DQ8 is the third most common haplotype in insulin-dependent diabetic (IDDM) patients and has the highest haplotype-specific absolute risk for IDDM. Cw1, B56, DR4, DQ8 haplotypes containing HLA-A alleles other than A2 are infrequent in the population and are not associated with IDDM. Comparison of the A2 and non-A2 haplotypes at the DNA level showed that they were identical at HLA-B,-DR, and -DQ loci. Evidence that class I alleles confer susceptibility to IDDM was obtained from the two HLA-C, -B, -DR and -DQ haplotypes most frequently found in IDDM patients in Finland. A24, A3 and A2 on the Cw3, B62, DR4, DQ8 haplotype, and A28, A2 and A1 on the Cw7, B8, DR3, DQ2 were all found to be associated with IDDM. In Finland these seven haplotypes, including A2, Cw1, B56, DR4, DQ8, account for 33% of diabetic haplotypes and 10.3% of non-diabetic haplotypes (p〈0.00001). The contribution of the class I region to IDDM susceptibility was also apparent in those IDDM patients lacking the disease-predisposing class II alleles. Significantly more non-DR3/non-DR4 IDDM patients (47 of 55) possessed two of the IDDM-associated HLA-A alleles compared to non-DR3/non-DR4 control subjects (40 of 58; p=0.038). Moreover, IDDM patients confirmed by oligotyping as unable to form a ‘diabetes-susceptibility’ DQ heterodimer, tended to possess two diabetes-associated HLA-A alleles (12 of 13) compared to control subjects (12 of 20; p=0.056).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400951
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  • 7
    Electronic Resource
    Electronic Resource
    A gene in the HLA class I region contributes to susceptibility to IDDM in the Finnish population (1994)
    Springer
    Diabetologia 37 (1994), S. 937-944 
    Details
    ISSN: 1432-0428
    Keywords: Key words Genetics ; haplotype ; HLA-A ; HLA-DQ ; HLA-DR ; tumour necrosis factor ; diabetes mellitus.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In Finland the haplotype A2, Cw1, B56, DR4, DQ8 is the third most common haplotype in insulin-dependent diabetic (IDDM) patients and has the highest haplotype-specific absolute risk for IDDM. Cw1, B56, DR4, DQ8 haplotypes containing HLA-A alleles other than A2 are infrequent in the population and are not associated with IDDM. Comparison of the A2 and non-A2 haplotypes at the DNA level showed that they were identical at HLA-B, -DR, and -DQ loci. Evidence that class I alleles confer susceptibility to IDDM was obtained from the two HLA-C, -B, -DR and -DQ haplotypes most frequently found in IDDM patients in Finland. A24, A3 and A2 on the Cw3, B62, DR4, DQ8 haplotype, and A28, A2 and A1 on the Cw7, B8, DR3, DQ2 were all found to be associated with IDDM. In Finland these seven haplotypes, including A2, Cw1, B56, DR4, DQ8, account for 33 % of diabetic haplotypes and 10.3 % of non-diabetic haplotypes (p 〈 0.00001). The contribution of the class I region to IDDM susceptibility was also apparent in those IDDM patients lacking the disease-predisposing class II alleles. Significantly more non-DR3/non-DR4 IDDM patients (47 of 55) possessed two of the IDDM-associated HLA-A alleles compared to non-DR3/non-DR4 control subjects (40 of 58; p = 0.038). Moreover, IDDM patients confirmed by oligotyping as unable to form a ’diabetes-susceptibility' DQ heterodimer, tended to possess two diabetes-associated HLA-A alleles (12 of 13) compared to control subjects (12 of 20; p = 0.056). [Diabetologia (1994) 37: 937–944]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400951
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