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

Author:
  • Lina Åkesson
  • Johan Trygg
  • Jessica Fuller
  • Rasmus Madsen
  • Jon Gabrielsson
  • Stephen Bruce
  • Hans Stenlund
  • Terry Tupling
  • Ranae Pefley
  • Torbjorn Lundstedt
  • Åke Lernmark
  • Thomas Moritz
Publishing year: 2011
Language: English
Pages: 593-603
Publication/Series: Metabolomics
Volume: 7
Issue: 4
Document type: Journal article
Publisher: Springer

Abstract english

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.

Keywords

  • Endocrinology and Diabetes
  • Type 1 diabetes
  • Metabolomics
  • OPLS-DA
  • Dynamic modeling

Other

Published
  • Diabetes and Celiac Unit
  • ISSN: 1573-3882
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79

60:11:015

Jan Waldenströms gata 35, Malmö

33

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00