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Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study
Vanessa D. de Mello, Jussi Paananen, Jaana Lindström and 16 more
Scientific Reports · 2017 · CC BY
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.
References 54
- 1.
Wang T. J.. Metabolite profiles and the risk of developing diabetes. Nat. Med. 17, 448–453 (2011 ).
Not in our library10.1038/nm.2307
- 2.
Floegel A.. Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach. Diabetes 62, 639–648 (2013 ).
Not in our library10.2337/db12-0495
- 3.
Menni C.. Biomarkers for type 2 diabetes and impaired fasting glucose using a nontargeted metabolomics approach. Diabetes 62, 4270–4276 (2013 ).
Not in our library10.2337/db13-0570
- 4.
- 5.
Hanhineva K.. Nontargeted metabolite profiling discriminates diet-specific biomarkers for consumption of whole grains, fatty fish, and bilberries in a randomized controlled trial. J. Nutr. 145, 7–17 (2015 ).
Not in our library10.3945/jn.114.196840
- 6.
Lindström J.. Improved lifestyle and decreased diabetes risk over 13 years: long-term follow-up of the randomised Finnish Diabetes Prevention Study (DPS). Diabetologia 56, 284–293 (2013 ).
Not in our library10.1007/s00125-012-2752-5
- 7.
de Mello V. D.. Insulin secretion and its determinants in the progression of impaired glucose tolerance to type 2 diabetes in impaired glucose-tolerant individuals: the Finnish Diabetes Prevention Study. Diabetes Care 35, 211–217 (2012 ).
Not in our library10.2337/dc11-1272
- 8.
Lankinen M. A.. Plasma fatty acids as predictors of glycaemia and type 2 diabetes. Diabetologia 58, 2533–2544 (2015 ).
Not in our library10.1007/s00125-015-3730-5
- 9.
Rolandsson O.. How to diagnose and classify diabetes in primary health care: lessons learned from the Diabetes Register in Northern Sweden (DiabNorth). Scand. J. Prim. Health Care 30, 81–87 (2012 ).
Not in our library10.3109/02813432.2012.675565
- 10.
Smith E. A. & Macfarlane G. T. Enumeration of human colonic bacteria producing phenolic and indolic compounds: effects of pH, carbohydrate availability and retention time on dissimilatory aromatic amino acid metabolism. J. Appl. Bacteriol. 81, 288–302 (1996 ).
Not in our library10.1111/j.1365-2672.1996.tb04331.x
- 11.
Smith E. A. & Macfarlane G. T. Formation of Phenolic and Indolic Compounds by Anaerobic Bacteria in the Human Large Intestine. Microb. Ecol. 33, 180–188 (1997 ).
Not in our library10.1007/s002489900020
- 12.
Wikoff W. R.. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc. Natl. Acad. Sci. USA 106, 3698–3703 (2009 ).
Not in our library10.1073/pnas.0812874106
- 13.
Haeusler R. A., Astiarraga B., Camastra S., Accili D. & Ferrannini E. Human insulin resistance is associated with increased plasma levels of 12alpha-hydroxylated bile acids. Diabetes 62, 4184–4191 (2013 ).
Not in our library10.2337/db13-0639
- 14.
Guasch-Ferré M.. Dietary fat intake and risk of cardiovascular disease and all-cause mortality in a population at high risk of cardiovascular disease. The American Journal of Clinical Nutrition(2015 ).
Not in our library10.3945/ajcn.115.116046
- 15.
- 16.
Garber A. J. Incretin effects on beta-cell function, replication, and mass: the human perspective. Diabetes Care 34 Suppl 2, S258–63 (2011 ).
Not in our library10.2337/dc11-s230
- 17.
Chyan Y. J.. Potent neuroprotective properties against the Alzheimer beta-amyloid by an endogenous melatonin-related indole structure, indole-3-propionic acid. J. Biol. Chem. 274, 21937–21942 (1999 ).
Not in our library10.1074/jbc.274.31.21937
- 18.
Karbownik M.. Indole-3-propionic acid, a melatonin-related molecule, protects hepatic microsomal membranes from iron-induced oxidative damage: relevance to cancer reduction. J. Cell. Biochem. 81, 507–513 (2001 ).
Not in our library
- 19.
Halban P. A.. Beta-Cell Failure in Type 2 Diabetes: Postulated Mechanisms and Prospects for Prevention and Treatment. Diabetes Care 37, 1751–1758 (2014 ).
Not in our library10.2337/dc14-0396
- 20.
Lutz T. A. & Meyer U. Amylin at the interface between metabolic and neurodegenerative disorders. Front. Neurosci. 9, 216 (2015 ).
Not in our library10.3389/fnins.2015.00216
- 21.
Haro C.. Two healthy diets modulate gut microbial community improving insulin sensitivity in a human obese population. J. Clin. Endocrinol. Metab. 101, 233–242 (2016 ).
Not in our library10.1210/jc.2015-3351
- 22.
Marchesi J. R.. The gut microbiota and host health: a new clinical frontier. Gut 65, 330–339 (2016 ).
Not in our library10.1136/gutjnl-2015-309990
- 23.
De Filippis,. F.. High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut(2015 ).
Not in our library10.1136/gutjnl-2015-309957
- 24.
Landberg R., Aman P., Hallmans G. & Johansson I. Long-term reproducibility of plasma alkylresorcinols as biomarkers of whole-grain wheat and rye intake within Northern Sweden Health and Disease Study Cohort. Eur. J. Clin. Nutr. 67, 259–263 (2013 ).
Not in our library10.1038/ejcn.2013.10
- 25.
- 26.
Qin J.. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 55–60 (2012 ).
Not in our library10.1038/nature11450
- 27.
Soga T.. Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor. Biochem. Biophys. Res. Commun. 326, 744–751 (2005).
Not in our library10.1016/j.bbrc.2004.11.120
- 28.
Yea K.. Lysophosphatidylcholine activates adipocyte glucose uptake and lowers blood glucose levels in murine models of diabetes. J. Biol. Chem. 284, 33833–33840 (2009 ).
Not in our library10.1074/jbc.m109.024869
- 29.
Pedersen H. K.. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature 535, 376–381 (2016 ).
Not in our library10.1038/nature18646
- 30.
Wang X.. Inflammatory markers and risk of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care 36, 166–175 (2013 ).
Not in our library10.2337/dc12-0702
- 31.
Liu C.. Adiponectin, TNF-alpha and inflammatory cytokines and risk of type 2 diabetes: A systematic review and meta-analysis. Cytokine 86, 100–109 (2016 ).
Not in our library10.1016/j.cyto.2016.06.028
- 32.
Pfeuffer M. & Jaudszus A. Pentadecanoic and Heptadecanoic Acids: Multifaceted Odd-Chain Fatty Acids. Adv. Nutr. 7, 730–734 (2016 ).
Not in our library10.3945/an.115.011387
- 33.
- 34.
- 35.
Fu J.. The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids. Circ. Res. 117, 817–824 (2015 ).
Not in our library10.1161/circresaha.115.306807
- 36.
Wang-Sattler R.. Novel biomarkers for pre-diabetes identified by metabolomics. Mol. Syst. Biol. 8, 615 (2012 ).
Not in our library10.1038/msb.2012.43
- 37.
Walford G. A.. Metabolite traits and genetic risk provide complementary information for the prediction of future type 2 diabetes. Diabetes Care 37, 2508–2514 (2014 ).
Not in our library10.2337/dc14-0560
- 38.
Wittenbecher C.. Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes. Am. J. Clin. Nutr. 101, 1241–1250 (2015 ).
Not in our library10.3945/ajcn.114.099150
- 39.
Wurtz P.. Circulating metabolite predictors of glycemia in middle-aged men and women. Diabetes Care 35, 1749–1756 (2012 ).
Not in our library10.2337/dc11-1838
- 40.
Wurtz P.. Branched-chain and aromatic amino acids are predictors of insulin resistance in young adults. Diabetes Care 36, 648–655 (2013 ).
Not in our library10.2337/dc12-0895
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