Early infant growth is associated with the risk of islet autoimmunity in genetically susceptible children

Authors

  • Andreas Beyerlein,

    1. Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany
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    • These authors contributed equally to this study.
  • Elisabeth Thiering,

    1. Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg, Germany
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    • These authors contributed equally to this study.
  • Maren Pflueger,

    1. Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany
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  • Martin Bidlingmaier,

    1. Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, LMU München, Munich, Germany
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  • Joanna Stock,

    1. Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany
    2. Forschergruppe Diabetes e.V., Neuherberg, Germany
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  • Annette Knopff,

    1. Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany
    2. Forschergruppe Diabetes e.V., Neuherberg, Germany
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  • Christiane Winkler,

    1. Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany
    2. Forschergruppe Diabetes e.V., Neuherberg, Germany
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  • Joachim Heinrich,

    1. Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg, Germany
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  • Anette-Gabriele Ziegler

    Corresponding author
    1. Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany
    2. Forschergruppe Diabetes e.V., Neuherberg, Germany
    • Corresponding author: Prof. Dr Anette-Gabriele Ziegler,

      Institute of Diabetes Research,

      Helmholtz Zentrum München,

      Ingolstaedter Landstr. 1,

      85764 Neuherberg,

      Germany.

      Tel: +49 89 3187 2896;

      fax: +49 89 3187 3144;

      email: anziegler@lrz.uni-muenchen.de

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Abstract

Background

Islet autoimmunity commonly develops early in infancy. We assessed whether specific parameters of early growth (including weight gain) were associated with the development of islet autoimmunity in children of type 1 diabetes patients, taking individual developmental patterns into account.

Methods

Growth parameters were estimated in n = 1011 children followed from birth in the prospective BABYDIAB and BABYDIET studies using longitudinal models. Cox proportional hazard models, adjusted for study, sex, gestational age, birth weight percentile, and maternal type 1 diabetes status, were calculated to assess hazard ratios (HR) for islet autoimmunity with corresponding 95% confidence intervals (95% CI) by 2 SD increases in growth parameters. In a subset of n = 170 infants, we investigated whether the growth hormones insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) were in the causal pathway.

Results

We found an early age at infant body mass index (BMI) peak to be associated with the development of islet autoimmunity [HR 0.60 (95% CI 0.41–0.87), per 2 SD increase in age]. Islet autoimmunity was also associated with BMI difference between infant BMI peak and childhood BMI rebound [HR 1.52 (95% CI 1.04–2.22)], but not after adjustment for age at infant BMI peak, and not with other parameters such as peak height and weight velocity during infancy. Serum concentrations of IGF-1 and IGFBP-3 at birth, 9 months, and 2 yr, respectively, were not significantly different between children with and without later islet autoimmunity.

Conclusions

Variations in early growth rate have subtle effects on the risk of islet autoimmunity with growth hormones unlikely to be in the causal pathway.

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