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Brief Communication: Early Appearance of Islet Autoantibodies Predicts Childhood Type 1 Diabetes in Offspring of Diabetic Parents

Michael Hummel, MD; Ezio Bonifacio, PhD; Sandra Schmid, PhD; Markus Walter, MD; Annette Knopff; and Anette-G Ziegler, MD
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From Diabetes Research Institute and Academic Hospital Schwabing, Munich, Germany, and Istituto Scientifico San Raffaele, Milan, Italy.

Acknowledgments: The authors thank Andrea Baumgarten, Ulrike Mollenhauer, Doris Huber, Kerstin Koczwara, Katharina Warncke, and Mike Schenker for expert technical assistance. They also thank all pediatricians and family doctors in Germany for participation in the BABYDIAB study.

Grant Support: By grants from the Juvenile Diabetes Research Foundation (JDRF #1-2003-646), the Stiftung ‘Das Zuckerkranke Kind’, the Bundesministerium für Forschung und Technologie (BMFT 01KD89030), and the Deutsche Diabetesgesellschaft (Dr. Buding-Stiftung).

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Anette-G. Ziegler, MD, Institut für Diabetesforschung, Kölner Platz 1, D-80804 München, Germany; e-mail, anziegler@lrz.uni-muenchen.de.

Current Author Addresses: Dr. Hummel: Academic Hospital Schwabing, Kölner Platz 1, D-80804 München, Germany.

Dr. Bonifacio: Immunology of Diabetes, San Raffaele Scientific Institute, Via Olgettina 60, I-20132 Milan, Italy.

Drs. Schmid, Walter, and Ziegler, and Ms. Knopff: Diabetes Research Institute, Kölner Platz 1, D-80804 München, Germany.

Author Contributions: Conception and design: M. Hummel, A. Ziegler.

Analysis and interpretation of the data: M. Hummel, E. Bonifacio, S. Schmid, A. Ziegler.

Drafting of the article: M. Hummel, E. Bonifacio, A. Ziegler.

Critical revision of the article for important intellectual content: E. Bonifacio, S. Schmid, M. Walter, A. Ziegler.

Final approval of the article: M. Hummel, E. Bonifacio, S. Schmid, M. Walter, A. Knopff, A. Ziegler.

Provision of the study materials or patients: M. Hummel, M. Walter, A. Ziegler.

Statistical expertise: E. Bonifacio.

Obtaining of funding: A. Ziegler.

Administrative, technical, or logistic support: E. Bonifacio, S. Schmid, M. Walter, A. Knopff, A. Ziegler.

Collection and assembly of the data: M. Hummel, S. Schmid, M. Walter, A. Knopff, A. Ziegler.

Ann Intern Med. 2004;140(11):882-886. doi:10.7326/0003-4819-140-11-200406010-00009
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Young-onset type 1 diabetes is increasing in frequency in most western countries and in particular in children younger than 5 years of age (1011). Children who have a first-degree relative with type 1 diabetes are at highest risk (2). Therefore, affected families are targeted for counseling and for investigative studies to identify causes of type 1 diabetes and to test intervention therapies (34, 1213). The German BABYDIAB study was designed to determine and stratify risk for islet autoimmunity and type 1 diabetes in offspring of parents with this form of diabetes.

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Life-table analysis of islet autoantibody development and diabetes development in BABYDIAB offspring.

A.The frequency of at least 1 autoantibody (autoantibodies to insulin [IAA], glutamic acid decarboxylase [GADA], or protein tyrosine phosphatase-like molecule IA-2 [IA-2A]). Autoantibody-positive events correspond to samples taken at all scheduled visits at approximately 9 months, 2 years, 5 years, and 8 years of age. B. Progression to multiple islet autoantibodies in autoantibody-positive BABYDIAB offspring. Offspring are categorized by their age at first autoantibody appearance as 9 months, 2 years, or 5 or 8 years of age, and follow-up is calculated from the age at the first positive sample to the age at the multiple autoantibody–positive sample or last sample. Progression to multiple autoantibodies was faster in 9-month (  = 0.002) and 2-year islet autoantibody–positive offspring (  = 0.005) than in offspring who became islet autoantibody positive at 5 or 8 years of age. C. Diabetes risk based on number of autoantibodies categorized as multiple (>1 or ≥ 2 of IAA, GADA, or IA-2A) or single (1 of IAA, GADA, or IA-2A). Follow-up is calculated from the age at the first positive sample to the age at diabetes onset or last contact. D. Diabetes risk based on the age when offspring first became positive for multiple islet autoantibodies. Follow-up is calculated from the age at the first multiple islet autoantibody–positive sample to the age at diabetes onset or last contact. The risk for diabetes increased in offspring with multiple autoantibodies (  < 0.001) compared with single autoantibodies and was directly related to the age when multiple autoantibodies appeared (  = 0.04, 9 months vs. 2 years;  = 0.04, 9 months vs. 5 or 8 years).

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Summary for Patients

Development of Islet Cell Autoantibodies and Type 1 Diabetes

The summary below is from the full report titled “Brief Communication: Early Appearance of Islet Autoantibodies Predicts Childhood Type 1 Diabetes in Offspring of Diabetic Parents.” It is in the 1 June 2004 issue of Annals of Internal Medicine (volume 140, pages 882-886). The authors are M. Hummel, E. Bonifacio, S. Schmid, M. Walter, A. Knopff, and A.-G. Ziegler.


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