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Serum metabolite signature predicts the acute onset of diabetes in spontaneously diabetic congenic BB rats

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Abstract

The clinical presentation of type 1 diabetes is preceded by a prodrome of beta cell autoimmunity. We probed the short period of subtle metabolic abnormalities, which precede the acute onset of diabetes in the spontaneously diabetic BB rat, by analyzing the serum metabolite profile detected with combined gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS). We found that the metabolite pattern prior to diabetes included 17 metabolites, which differed between individual diabetes prone (DP) BB rats and their age and sex matched diabetes resistant (DR) littermates. As the metabolite signature at the 40 days of age baseline failed to distinguish DP from DR, there was a brief 10-day period after which the diabetes prediction pattern was observed, that includes fatty acids (e.g. oleamide), phospholipids (e.g. phosphocholines) and amino acids (e.g. isoleucine). It is concluded that distinct changes in the serum metabolite pattern predict type 1 diabetes and precede the appearance of insulitis in spontaneously diabetic BB DP rats. This observation should prove useful to dissect mechanisms of type 1 diabetes.

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Acknowledgments

Krister Lundgren and Inga-Britt Carlsson are acknowledged for help with the metabolomics analyses. This study was supported by the Juvenile Diabetes Research Foundation (grant 1-2008-1011), the Swedish Research Council (621-2005-5635, 521-2007-2666), the Swedish Foundation for Strategic Research, the Knut and Alice Wallenberg Foundation, the Kempe Foundation, and SLU.

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Authors and Affiliations

  1. Department of Clinical Sciences, Diabetes and Celiac Disease Unit, Lund University, Malmö, Sweden

    Lina Åkesson & Åke Lernmark

  2. Computational Life Science Cluster, KBC, Umeå University, Umeå, 90187, Sweden

    Johan Trygg, Rasmus Madsen & Hans Stenlund

  3. Department of Medicine, University of Washington, Seattle, WA, USA

    Jessica M. Fuller, Terry Tupling, Ranae Pefley & Åke Lernmark

  4. AcureOmics AB, Tvistevägen 48, SE, 907 36, Umeå, Sweden

    Jon Gabrielsson

  5. Nestlé Research Center–Lausanne, Nestec Ltd, CH-1000 Lausanne 26, Vers-chez-les-Blanc, Switzerland

    Stephen Bruce

  6. Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, SE, 901 87, Umeå, Sweden

    Stephen Bruce & Thomas Moritz

  7. AcurePharma AB, Ulleråkersvägen 38, SE, 756 43, Uppsala, Sweden

    Torbjörn Lundstedt

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  1. Lina Åkesson
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Correspondence to Thomas Moritz.

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11306_2011_278_MOESM1_ESM.eps

Figure 1-S. An overview of the serum metabolite profiles from all DP and DR samples at the 39–40 days of age baseline. The PCA scores plot (t1-t2) of the normoglycemic DP (n = 16), DR1 (n = 7) and DR2 (n = 12) rats reveals no systematic difference in the serum metabolite profiles at baseline day. The metabolite profiles were analyzed by LC/MS. (EPS 1650 kb)

11306_2011_278_MOESM2_ESM.eps

Figure 2-S Cross validated OPLS-DA Prediction of Class (PoC) of onset of hyperglycemia in the DP rats compared to the DR rats. (EPS 785 kb)

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Åkesson, L., Trygg, J., Fuller, J.M. et al. Serum metabolite signature predicts the acute onset of diabetes in spontaneously diabetic congenic BB rats. Metabolomics 7, 593–603 (2011). https://doi.org/10.1007/s11306-011-0278-3

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