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Research article2017Peer reviewedOpen access

Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study

de Mello, Vanessa D.; Paananen, Jussi; Lindstrom, Jaana; Lankinen, Maria A.; Shi, Lin; Kuusisto, Johanna; Pihlajamaki, Jussi; Auriola, Seppo; Lehtonen, Marko; Rolandsson, Olov; Bergdahl, Ingvar A.; Nordin, Elise; Ilanne-Parikka, Pirjo; Keinanen-Kiukaanniemi, Sirkka; Landberg, Rikard; Eriksson, Johan G.; Tuomilehto, Jaakko; Hanhineva, Kati; Uusitupa, Matti

Abstract

Wide-scale profiling technologies including metabolomics broaden the possibility of novel discoveries related to the pathogenesis of type 2 diabetes (T2D). By applying non-targeted metabolomics approach, we investigated here whether serum metabolite profile predicts T2D in a well-characterized study population with impaired glucose tolerance by examining two groups of individuals who took part in the Finnish Diabetes Prevention Study (DPS); those who either early developed T2D (n = 96) or did not convert to T2D within the 15-year follow-up (n = 104). Several novel metabolites were associated with lower likelihood of developing T2D, including indole and lipid related metabolites. Higher indolepropionic acid was associated with reduced likelihood of T2D in the DPS. Interestingly, in those who remained free of T2D, indolepropionic acid and various lipid species were associated with better insulin secretion and sensitivity, respectively. Furthermore, these metabolites were negatively correlated with low-grade inflammation. We replicated the association between indolepropionic acid and T2D risk in one Finnish and one Swedish population. We suggest that indolepropionic acid, a gut microbiota-produced metabolite, is a potential biomarker for the development of T2D that may mediate its protective effect by preservation of alpha-cell function. Novel lipid metabolites associated with T2D may exert their effects partly through enhancing insulin sensitivity.

Published in

Scientific Reports
2017, Volume: 7, article number: 46337
Publisher: NATURE PUBLISHING GROUP

      SLU Authors

        • Sustainable Development Goals

        SDG3 Ensure healthy lives and promote well-being for all at all ages

        UKÄ Subject classification

        Physiology

        Publication identifier

        DOI: https://doi.org/10.1038/srep46337

        Permanent link to this page (URI)

        https://res.slu.se/id/publ/94071