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Sci Rep. 2017 Apr 11;7:46337. doi: 10.1038/srep46337.

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

Author information

1
Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
2
Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
3
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
4
Department of Food Science, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden.
5
Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Finland.
6
Clinical Nutrition and Obesity Center, Kuopio University Hospital, Finland.
7
School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
8
LC-MS Metabolomics Center, Biocenter Kuopio, Kuopio, Finland.
9
Department of Public Health and Clinical Medicine, Family Medicine, Umeå University, Umeå, Sweden.
10
Department of Biobank Research, Umeå University, Umeå, Sweden.
11
The Diabetes Centre, Finnish Diabetes Association, Tampere, Finland.
12
Science Center, Tampere University Hospital, Tampere, Finland.
13
Institute of Health Sciences, University of Oulu, Oulu, Finland.
14
Unit of General Practice, Oulu University Hospital, Oulu, Finland.
15
Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
16
Department of General Practice and Primary Health, University of Helsinki, Helsinki, Finland.
17
Folkhälsan Research Center, Helsinki, Finland.
18
Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland.
19
Vaasa Central Hospital, Vaasa, Finland.
20
Center for Vascular Prevention, Danube-University Krems, Austria.
21
Saudi Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
22
Research Unit, Kuopio University Hospital, Kuopio, Finland.

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.

PMID:
28397877
PMCID:
PMC5387722
DOI:
10.1038/srep46337
[Indexed for MEDLINE]
Free PMC Article

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