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

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

From Diabetes Research Institute and Academic Hospital Schwabing, Munich, Germany, and Istituto Scientifico San Raffaele, Milan, Italy.

Abstract

Background: The development of type 1 diabetes mellitus is preceded by autoimmunity against islet β cells.

Objective: To determine the risk for islet autoimmunity and childhood diabetes in offspring of affected parents.

Design: Prospective cohort study.

Setting: German BABYDIAB study.

Participants: 1610 offspring of parents with type 1 diabetes.

Measurements: Autoantibodies to islet autoantigens were measured at 9 months, 2 years, 5 years, and 8 years of age.

Results: By 5 years of age, the frequency of islet autoantibodies was 5.9% (95% CI, 4.6% to 7.2%), the frequency of multiple islet autoantibodies was 3.5% (CI, 2.5% to 4.5%), and the frequency of diabetes was 1.5% (CI, 0.9% to 2.1%). The risk for diabetes was highest in offspring with multiple autoantibodies (40% within 5 years vs. 3% in offspring with single autoantibodies; P = 0.005). Progression to multiple islet autoantibodies was fastest in children who were autoantibody positive by age 2 years (P < 0.001), and progression to diabetes was inversely related to the age of positivity for multiple autoantibodies (P = 0.02).

Limitations: The findings are limited to childhood diabetes in affected families.

Conclusions: Childhood autoimmune diabetes is associated with autoimmunity that starts before 2 years of age.

Article and Author Information

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{at}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.