Vertaisarvioitu alkuperäisartikkeli tai data-artikkeli tieteellisessä aikakauslehdessä (A1)

Longitudinal Metabolome-Wide Signals Prior to the Appearance of a First Islet Autoantibody in Children Participating in the TEDDY Study




Julkaisun tekijät: Li Q, Parikh H, Butterworth MD, Lernmark A, Hagopian W, Rewers M, She JX, Toppari J, Ziegler AG, Akolkar B, Fiehn O, Fan SL, Krischer JP; and the TEDDY Study Group

Kustantaja: AMER DIABETES ASSOC

Julkaisuvuosi: 2020

Journal: Diabetes

Tietokannassa oleva lehden nimi: DIABETES

Lehden akronyymi: DIABETES

Volyymi: 69

Julkaisunumero: 3

Sivujen määrä: 12

ISSN: 0012-1797

DOI: http://dx.doi.org/10.2337/db19-0756

Verkko-osoite: https://diabetesjournals.org/diabetes/article/69/3/465/39778/Longitudinal-Metabolome-Wide-Signals-Prior-to-the


Tiivistelmä
Children at increased genetic risk for type 1 diabetes (T1D) after environmental exposures may develop pancreatic islet autoantibodies (IA) at a very young age. Metabolic profile changes over time may imply responses to exposures and signal development of the first IA. Our present research in The Environmental Determinants of Diabetes in the Young (TEDDY) study aimed to identify metabolome-wide signals preceding the first IA against GAD (GADA-first) or against insulin (IAA-first). We profiled metabolomes by mass spectrometry from children's plasma at 3-month intervals after birth until appearance of the first IA. A trajectory analysis discovered each first IA preceded by reduced amino acid proline and branched-chain amino acids (BCAAs), respectively. With independent time point analysis following birth, we discovered dehydroascorbic acid (DHAA) contributing to the risk of each first IA, and gamma-aminobutyric acid (GABAs) associated with the first autoantibody against insulin (IAA-first). Methionine and alanine, compounds produced in BCAA metabolism and fatty acids, also preceded IA at different time points. Unsaturated triglycerides and phosphatidylethanolamines decreased in abundance before appearance of either autoantibody. Our findings suggest that IAA-first and GADA-first are heralded by different patterns of DHAA, GABA, multiple amino acids, and fatty acids, which may be important to primary prevention of T1D.


Last updated on 2022-10-02 at 13:11