title: Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study.
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 β-cell function. Novel lipid metabolites associated with T2D may exert their effects partly through enhancing insulin sensitivity.
authors.affiliation: Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
authors.forename: Vanessa D
authors.initials: VD
authors.lastname: de Mello
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Paananen
authors.affiliation: Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Lindström
authors.affiliation: Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Lankinen
authors.affiliation: Department of Food Science, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Lin
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Kuusisto
authors.affiliation: Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.|Clinical Nutrition and Obesity Center, Kuopio University Hospital, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Pihlajamäki
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.|LC-MS Metabolomics Center, Biocenter Kuopio, Kuopio, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Auriola
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.|LC-MS Metabolomics Center, Biocenter Kuopio, Kuopio, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Lehtonen
authors.affiliation: Department of Public Health and Clinical Medicine, Family Medicine, Umeå University, Umeå, Sweden.
authors.forename: Olov
authors.initials: O
authors.lastname: Rolandsson
authors.affiliation: Department of Biobank Research, Umeå University, Umeå, Sweden.
authors.forename: Ingvar A
authors.initials: IA
authors.lastname: Bergdahl
authors.affiliation: Department of Food Science, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Elise
authors.initials: E
authors.lastname: Nordin
authors.affiliation: The Diabetes Centre, Finnish Diabetes Association, Tampere, Finland.|Science Center, Tampere University Hospital, Tampere, Finland.
authors.forename: Pirjo
authors.initials: P
authors.lastname: Ilanne-Parikka
authors.affiliation: Institute of Health Sciences, University of Oulu, Oulu, Finland.|Unit of General Practice, Oulu University Hospital, Oulu, Finland.
authors.forename: Sirkka
authors.initials: S
authors.lastname: Keinänen-Kiukaanniemi
authors.affiliation: Department of Food Science, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden.|Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Rikard
authors.initials: R
authors.lastname: Landberg
authors.affiliation: Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.|Department of General Practice and Primary Health, University of Helsinki, Helsinki, Finland.|Folkhälsan Research Center, Helsinki, Finland.|Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland.|Vaasa Central Hospital, Vaasa, Finland.
authors.forename: Johan G
authors.initials: JG
authors.lastname: Eriksson
authors.affiliation: Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.|Center for Vascular Prevention, Danube-University Krems, Austria.|Saudi Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Tuomilehto
authors.affiliation: Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.|LC-MS Metabolomics Center, Biocenter Kuopio, Kuopio, Finland.
authors.forename: Kati
authors.initials: K
authors.lastname: Hanhineva
authors.affiliation: Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.|Research Unit, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Uusitupa
mesh_terms: D000368:Aged; D000596:Amino Acids / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D015415:Biomarkers; D002097:C-Reactive Protein / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000209:etiology* / Q000378:metabolism; D004043:Dietary Fiber; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D007211:Indoles / Q000009:adverse effects*; D007328:Insulin / Q000378:metabolism; D008019:Life Style; D050356:Lipid Metabolism; D008055:Lipids / Q000009:adverse effects*; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D011159:Population Surveillance; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D000596:Amino Acids; D001647:Bile Acids and Salts; D015415:Biomarkers; D004043:Dietary Fiber; D007211:Indoles; D007328:Insulin; D008055:Lipids; C015292:indolepropionic acid; D002097:C-Reactive Protein