Scholarlink

Aims/hypothesis <p>Islet autoimmunity during presymptomatic type 1 diabetes is heterogeneous. We hypothesised that a positive family history of type 1 diabetes is associated with specific characteristics of the autoimmune process resulting in clinical diabetes. In a prospective birth cohort study, we compared the initiation and evolution of islet autoimmunity and the rate of progression from islet autoimmunity to diabetes between children with and without a first-degree relative (FDR) with type 1 diabetes.</p> Methods <p>In the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study, we prospectively followed children with HLA-conferred susceptibility from birth for the appearance of islet autoantibodies (IAA, GADA, IA-2A, ZnT8A), further development of islet autoimmunity, and progression to clinical diabetes. The presence of type 1 diabetes among their FDRs was recorded at the time of birth, and the family history data was updated during the follow-up period.</p> Results <p>Among a total of 1334 children with confirmed positivity for at least one islet autoantibody, 145 (10.9%) had one or more FDRs with type 1 diabetes at the time of birth (FDR+). During a median follow-up period of 8.6 years, FDRs of an additional 87 children developed type 1 diabetes (FDR− FDR+). At seroconversion, both FDR+ and FDR− FDR+ children were significantly more often positive for GADA and multiple autoantibodies than children without affected FDRs (FDR−). The seroconversion age was similar between the three groups (median 2.7 vs 2.1 vs 3.0 years in FDR+, FDR− FDR+ and FDR− children, respectively). During the follow-up period, FDR+ and FDR− FDR+ children more often had IAA, GADA, IA-2A and multiple autoantibodies than FDR− children, and progressed more frequently to diabetes (55.9 vs 57.5 vs 38.9%, respectively). Time from seroconversion to clinical diabetes was significantly shorter in FDR+ children compared with FDR− children (2.7 vs 3.6 years). Children with paternal type 1 diabetes at birth (<i>n</i>=71; i.e., the father had type 1 diabetes) were twice as often positive for multiple autoantibodies at seroconversion as those with maternal type 1 diabetes (<i>n</i>=50; i.e. the mother had type 1 diabetes) (39.4% vs 20.0%).</p> Conclusions/interpretation <p>At seroconversion, genetically susceptible children who had one or more FDRs with type 1 diabetes, especially an affected father, were more often positive for GADA and multiple islet autoantibodies. During the follow-up period, children with an affected FDR were more often positive for IAA, GADA and IA-2A, and progressed to clinical type 1 diabetes more often and faster than children without an affected FDR. These data should be considered when designing intervention and screening studies.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Islet autoimmunity and progression to type 1 diabetes in the Finnish DIPP study: comparison between genetically susceptible children with and without an affected first-degree relative

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月8日

查看全文
  • Salla Kuusela,
  • Jaakko J. Koskenniemi,
  • Toni Valtanen,
  • Tytti Pokka,
  • Taina Härkönen,
  • Jorma Ilonen,
  • Johanna Lempainen,
  • Anni Kyrönniemi,
  • Jorma Toppari,
  • Mikael Knip,
  • Päivi Keskinen,
  • Riitta Veijola

摘要

Aims/hypothesis

Islet autoimmunity during presymptomatic type 1 diabetes is heterogeneous. We hypothesised that a positive family history of type 1 diabetes is associated with specific characteristics of the autoimmune process resulting in clinical diabetes. In a prospective birth cohort study, we compared the initiation and evolution of islet autoimmunity and the rate of progression from islet autoimmunity to diabetes between children with and without a first-degree relative (FDR) with type 1 diabetes.

Methods

In the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study, we prospectively followed children with HLA-conferred susceptibility from birth for the appearance of islet autoantibodies (IAA, GADA, IA-2A, ZnT8A), further development of islet autoimmunity, and progression to clinical diabetes. The presence of type 1 diabetes among their FDRs was recorded at the time of birth, and the family history data was updated during the follow-up period.

Results

Among a total of 1334 children with confirmed positivity for at least one islet autoantibody, 145 (10.9%) had one or more FDRs with type 1 diabetes at the time of birth (FDR+). During a median follow-up period of 8.6 years, FDRs of an additional 87 children developed type 1 diabetes (FDR− FDR+). At seroconversion, both FDR+ and FDR− FDR+ children were significantly more often positive for GADA and multiple autoantibodies than children without affected FDRs (FDR−). The seroconversion age was similar between the three groups (median 2.7 vs 2.1 vs 3.0 years in FDR+, FDR− FDR+ and FDR− children, respectively). During the follow-up period, FDR+ and FDR− FDR+ children more often had IAA, GADA, IA-2A and multiple autoantibodies than FDR− children, and progressed more frequently to diabetes (55.9 vs 57.5 vs 38.9%, respectively). Time from seroconversion to clinical diabetes was significantly shorter in FDR+ children compared with FDR− children (2.7 vs 3.6 years). Children with paternal type 1 diabetes at birth (n=71; i.e., the father had type 1 diabetes) were twice as often positive for multiple autoantibodies at seroconversion as those with maternal type 1 diabetes (n=50; i.e. the mother had type 1 diabetes) (39.4% vs 20.0%).

Conclusions/interpretation

At seroconversion, genetically susceptible children who had one or more FDRs with type 1 diabetes, especially an affected father, were more often positive for GADA and multiple islet autoantibodies. During the follow-up period, children with an affected FDR were more often positive for IAA, GADA and IA-2A, and progressed to clinical type 1 diabetes more often and faster than children without an affected FDR. These data should be considered when designing intervention and screening studies.

Graphical Abstract