Clinical, autoimmune, and genetic characteristics of very young children with type 1 diabetes. Childhood Diabetes in Finland (DiMe) Study Group.

Komulainen, Jorma; Kulmala, Petri; Savola, K.; Lounamaa, R; Ilonen, Jorma; Reijonen, Helena; Knip, Mikael; Åkerblom, Hans K.

doi:10.2337/diacare.22.12.1950

Cited by 182 publications

(161 citation statements)

References 3 publications

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“…These phenomena were equally pronounced in patients diagnosed before 1965 and in those diagnosed after 1990, which confirms a conserved age-dependent role for HLA DQ molecules in a changing environment. Similar age-dependent heterogeneity in frequencies of diabetes associated HLA haplotypes was reported earlier by our group and others [13,14].…”

Section: Discussionsupporting

confidence: 68%

Temporal changes in the frequencies of HLA genotypes in patients with Type 1 diabetes—indication of an increased environmental pressure?

et al. 2003

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Aims/hypothesis. The incidence of Type 1 diabetes has increased 2.5 times during the time period from 1966 to 2000 in Finland -a general trend seen in almost all developed countries that can only be explained by environmental factors. The aim of this study was to test the possible effect of a changing environment on distribution of genotypes associated with disease susceptibility. Methods. HLA DRB1-DQA1-DQB1 genes and two diabetes-associated polymorphisms at IDDM2 and IDDM12 were analyzed. The frequencies of genotypes were compared between cases diagnosed with childhood-onset Type 1 diabetes during the period of 1939-1965 (n=367) and those diagnosed between 1990 and 2001 (n=736). Chi-square statistics or the Fisher's Exact test were used for the comparison of frequencies of analyzed haplotypes and genotypes in the two groups.

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Section: Discussionsupporting

confidence: 68%

Temporal changes in the frequencies of HLA genotypes in patients with Type 1 diabetes—indication of an increased environmental pressure?

et al. 2003

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“…This wide variation in frequency may be attributed in part to the age range of the study population, since IA-2Abs decrease in frequency with increasing age at onset (17). Diagnostic sensitivity varies most with age in IAAs, decreasing from 50 -60% in the very young (below age 10 years) to ϳ10% among those diagnosed before 30 years of age (17,18,49). In addition, IAAs often may precede other autoimmune markers (9,18,50), which has led to the hypothesis that insulin may be an autoantigen in type 1 diabetes that plays a role early in the pathogenic process.…”

Section: Diabetes Classification and Daasmentioning

confidence: 98%

“…In children Ͻ2 years of age, ICA and IAA titers are higher than in older children and IA-2Abs are lower (49). In a study of 40 children in Los Angeles, diagnosed before 5 years of age, the frequency of positive IA-2Ab sera was also observed to be lower than in older children (28.6 vs. 77% in 0-to 5-year-old children vs. children 6 years or older) (54).…”

Section: Diabetes Classification and Daasmentioning

confidence: 99%

Autoantibodies in Diabetes

et al. 2005

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Islet cell autoantibodies are strongly associated with the development of type 1 diabetes. The appearance of autoantibodies to one or several of the autoantigens-GAD65, IA-2, or insulin-signals an autoimmune pathogenesis of ␤-cell killing. A ␤-cell attack may be best reflected by the emergence of autoantibodies dependent on the genotype risk factors, isotype, and subtype of the autoantibodies as well as their epitope specificity. It is speculated that progression to ␤-cell loss and clinical onset of type 1 diabetes is reflected in a developing pattern of epitopespecific autoantibodies. Although the appearance of autoantibodies does not follow a distinct pattern, the presence of multiple autoantibodies has the highest positive predictive value for type 1 diabetes. In the absence of reliable T-cell tests, dissection of autoantibody responses in subjects of genetic risk should prove useful in identifying triggers of islet autoimmunity by examining seroconversion and maturation of the autoantibody response that may mark time to onset of type 1 diabetes. The complexity of the disease process is exemplified by multiple clinical phenotypes, including autoimmune diabetes masquerading as type 2 diabetes in youth and adults. Autoantibodies may also provide prognostic information in clinically heterogeneous patient populations when examined longitudinally. Diabetes 54 (Suppl. 2):S52-S61, 2005

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“…In the very young, a linear and rapid progression toward exhaustion of the ␤-cell function is likely to occur, whereas in the adolescent, a longer prodrome followed by an acute precipitating factor (viral?) may be more common, based on available data (10). In LADA, we can speculate that multiple events may hit the ␤-cells in genetically susceptible subjects, leading to the decline of ␤-cell function.…”

Section: Definition and Pathogenesis -The Recent Newmentioning

confidence: 99%

Autoimmune Diabetes Not Requiring Insulin at Diagnosis (Latent Autoimmune Diabetes of the Adult)

2001

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Type 1 diabetes is caused by the immune-mediated destruction of islet insulin-secreting β-cells. This chronic destructive process is associated with both cellular and humoral immune changes in the peripheral blood that can be detected months or even years before the onset of clinical diabetes. Throughout this prediabetic period, metabolic changes, including altered glucose tolerance and reduced insulin secretion, deteriorate at variable rates and eventually result in clinical diabetes. A fraction of individuals with humoral immunological changes have clinical diabetes that initially is not insulin-requiring. The onset of diabetes in these patients is usually in adult life, and because their diabetes is at least initially not insulin-requiring, they appear clinically to be affected by type 2 diabetes. Such patients probably have the same disease process as patients with type 1 diabetes in that they have similar HLA genetic susceptibility as well as autoantibodies to islet antigens, low insulin secretion, and a higher rate of progression to insulin dependency. These patients are defined as being affected by an autoimmune type of diabetes not requiring insulin at diagnosis, which is also named latent autoimmune diabetes of the adult (LADA). Special attention should be paid to diagnose such patients because therapy may influence the speed of progression toward insulin dependency, and in this respect, efforts should be made to protect residual C-peptide secretion. LADA can serve as a model for designing new strategies for prevention of type 1 diabetes but also as a target group for prevention in its own right.

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Clinical, autoimmune, and genetic characteristics of very young children with type 1 diabetes. Childhood Diabetes in Finland (DiMe) Study Group.

Abstract: The clinical presentation of type 1 diabetes at a very young age is associated with severe metabolic decompensation, poorly preserved residual beta-cell function, strong humoral autoimmunity against islet cells and insulin, and strong HLA-defined disease susceptibility.

Cited by 182 publications

References 3 publications

Temporal changes in the frequencies of HLA genotypes in patients with Type 1 diabetes—indication of an increased environmental pressure?

Temporal changes in the frequencies of HLA genotypes in patients with Type 1 diabetes—indication of an increased environmental pressure?

Autoantibodies in Diabetes

Autoimmune Diabetes Not Requiring Insulin at Diagnosis (Latent Autoimmune Diabetes of the Adult)

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