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Accelerated progression from islet autoimmunity to diabetes is causing the escalating incidence of type 1 diabetes in young children.

ABSTRACT: The incidence of type 1 diabetes is rising worldwide, particularly in young children. Since type 1 diabetes is preceded by autoimmunity to islet antigens, there must be a consequent increase in the incidence of islet autoimmunity in young children or a more rapid rate of progression to diabetes once islet autoimmunity initiates. This study was to determine whether the incidence of islet autoimmunity or the rate of progression from autoimmunity to diabetes onset has changed over a 20-year period in children genetically predisposed to type 1 diabetes. Between 1989 and 2010, children who were first-degree relatives of patients with type 1 diabetes and who were born in Germany were prospectively followed from birth without intervention. A total of 324 children (BABYDIAB study) born between 1989 and 2000 and 216 children (TEDDY study) born between 2004 and 2010 with matched HLA genotypes were recruited before age 3 months and included for analysis. Children were followed for the development of autoantibodies to insulin, GAD, and IA-2, and for progression to diabetes. The cumulative frequency of diabetes by age 4 years was 2.5% (95% CI 0.8-4.2%) in BABYDIAB children and 6.2% (95% CI 2.3-10.1%) in TEDDY children (p = 0.03). The cumulative frequency of islet autoantibodies by age 4 years was similar in the children from both studies (11.3% vs 13.9%). Progression to diabetes from the development of islet autoantibodies was markedly increased in autoantibody-positive children from the more recently recruited TEDDY cohort (50% progression within 85.2 months for BABYDIAB children vs 9.6 months for TEDDY children; p = 0.009), also if children were further selected on the basis of high-risk HLA genotypes or the development of autoantibodies to multiple islet antigens (p = 0.01). The findings suggest that recent increasing incidence of type 1 diabetes in young children could be due to weakening of mechanisms that normally regulate autoimmune destruction of islet beta cells.

SUBMITTER: Ziegler AG

PROVIDER: S-EPMC3110538 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Accelerated progression from islet autoimmunity to diabetes is causing the escalating incidence of type 1 diabetes in young children.

Ziegler Anette-G AG Pflueger Maren M Winkler Christiane C Achenbach Peter P Akolkar Beena B Krischer Jeffrey P JP Bonifacio Ezio E

Journal of autoimmunity 20110303 1

The incidence of type 1 diabetes is rising worldwide, particularly in young children. Since type 1 diabetes is preceded by autoimmunity to islet antigens, there must be a consequent increase in the incidence of islet autoimmunity in young children or a more rapid rate of progression to diabetes once islet autoimmunity initiates. This study was to determine whether the incidence of islet autoimmunity or the rate of progression from autoimmunity to diabetes onset has changed over a 20-year period ...[more]

PMID: 21376535

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Project description:AIMS/HYPOTHESIS:We sought to assess the frequency, determinants and prognosis for future diabetes in individuals with islet autoimmunity and whether these factors differ depending on the age of onset of islet autoimmunity. METHODS:A prospective cohort (n = 2547) of children from the general population who had a high-risk HLA genotype and children who had a first-degree relative with type 1 diabetes were followed for up to 21 years. Those with the persistent presence of one or more islet autoantibodies were categorised as early-onset (<8 years of age, n = 143, median 3.3 years) or late-onset (?8 years of age, n = 64, median 11.1 years), and were followed for a median of 7.4 and 4.7 years, respectively. Progression to diabetes was evaluated by Kaplan-Meier analysis with logrank test. Factors associated with progression to diabetes were analysed using the parametric accelerated failure time model. RESULTS:Children with late-onset islet autoimmunity were more likely to be Hispanic or African-American than non-Hispanic white (p = 0.004), and less likely to be siblings of individuals with type 1 diabetes (p = 0.04). The frequencies of the HLA-DR3/4 genotype and non-HLA gene variants associated with type 1 diabetes did not differ between the two groups. However, age and HLA-DR3/4 were important predictors of rate of progression to both the presence of additional autoantibodies and type 1 diabetes. Late-onset islet autoimmunity was more likely to present with a single islet autoantibody (p = 0.01) and revert to an antibody-negative state (p = 0.01). Progression to diabetes was significantly slower in children with late-onset islet autoimmunity (p < 0.001). CONCLUSIONS/INTERPRETATION:A late onset of islet autoimmunity is more common in African-American and Hispanic individuals. About half of those with late-onset islet autoimmunity progress to show multiple islet autoantibodies and develop diabetes in adolescence or early adulthood. Further investigation of environmental determinants of late-onset autoimmunity may lead to an understanding of and ability to prevent adolescent and adult-onset type 1 diabetes.

Dataset Information

Accelerated progression from islet autoimmunity to diabetes is causing the escalating incidence of type 1 diabetes in young children.

Publications

Accelerated progression from islet autoimmunity to diabetes is causing the escalating incidence of type 1 diabetes in young children.

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