Identification of Serum Metabolites Associated With Risk of Type 2 Diabetes Using a Targeted Metabolomic Approach
Anna Floegel,Norbert Stefan,Zhonghao Yu,Kristin Mühlenbruch,Dagmar Drogan,Hans-Georg Joost,Andreas Fritsche,Hans-Ulrich Häring,Martin Hrabě de Angelis,Annette Peters,Michael Roden,Cornelia Prehn,Rui Wang-Sattler,Thomas Illig,Matthias B. Schulze,Jerzy Adamski,Heiner Boeing,Tobias Pischon +17 more
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TLDR
The data indicate that metabolic alterations, including sugar metabolites, amino acids, and choline-containing phospholipids, are associated early on with a higher risk of T2D.Abstract:
Metabolomic discovery of biomarkers of type 2 diabetes (T2D) risk may reveal etiological pathways and help to identify individuals at risk for disease. We prospectively investigated the association between serum metabolites measured by targeted metabolomics and risk of T2D in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam (27,548 adults) among all incident cases of T2D (n = 800, mean follow-up 7 years) and a randomly drawn subcohort (n = 2,282). Flow injection analysis tandem mass spectrometry was used to quantify 163 metabolites, including acylcarnitines, amino acids, hexose, and phospholipids, in baseline serum samples. Serum hexose; phenylalanine; and diacyl-phosphatidylcholines C32:1, C36:1, C38:3, and C40:5 were independently associated with increased risk of T2D and serum glycine; sphingomyelin C16:1; acyl-alkyl-phosphatidylcholines C34:3, C40:6, C42:5, C44:4, and C44:5; and lysophosphatidylcholine C18:2 with decreased risk. Variance of the metabolites was largely explained by two metabolite factors with opposing risk associations (factor 1 relative risk in extreme quintiles 0.31 [95% CI 0.21–0.44], factor 2 3.82 [2.64–5.52]). The metabolites significantly improved T2D prediction compared with established risk factors. They were further linked to insulin sensitivity and secretion in the Tubingen Family study and were partly replicated in the independent KORA (Cooperative Health Research in the Region of Augsburg) cohort. The data indicate that metabolic alterations, including sugar metabolites, amino acids, and choline-containing phospholipids, are associated early on with a higher risk of T2D.read more
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Human gut microbes impact host serum metabolome and insulin sensitivity
Helle Krogh Pedersen,Valborg Gudmundsdottir,Henrik Nielsen,Tuulia Hyötyläinen,Tuulia Hyötyläinen,Trine G. Nielsen,Benjamin A. H. Jensen,Kristoffer Forslund,Falk Hildebrand,Falk Hildebrand,Edi Prifti,Edi Prifti,Gwen Falony,Florence Levenez,Joël Doré,Ismo Mattila,Ismo Mattila,Damian R. Plichta,Päivi Pöhö,Päivi Pöhö,Lars Hellgren,Manimozhiyan Arumugam,Shinichi Sunagawa,Sara Vieira-Silva,Torben Jørgensen,Torben Jørgensen,Jacob Bak Holm,Kajetan Trošt,Karsten Kristiansen,Susanne Brix,Jeroen Raes,Jeroen Raes,Jun Wang,Torben Hansen,Torben Hansen,Peer Bork,Søren Brunak,Søren Brunak,Matej Orešič,Matej Orešič,Matej Orešič,S. Dusko Ehrlich,S. Dusko Ehrlich,Oluf Pedersen +43 more
TL;DR: It is shown how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals and suggested that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.
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Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future
TL;DR: More effective therapies to slow progressive loss of β-cell function are needed and additional long-term studies of drugs and bariatric surgery are needed to identify new ways to prevent and treat type 2 diabetes and thereby reduce the harmful effects of this disease.
Journal ArticleDOI
Metabolomics in Prediabetes and Diabetes: A Systematic Review and Meta-analysis
Marta Guasch-Ferré,Adela Hruby,Estefanía Toledo,Clary B. Clish,Miguel Ángel Martínez-González,Miguel Ángel Martínez-González,Jordi Salas-Salvadó,Frank B. Hu,Frank B. Hu +8 more
TL;DR: In studies using high-throughput metabolomics, several blood amino acids appear to be consistently associated with the risk of developing type 2 diabetes.
Journal ArticleDOI
Metabolite Profiling and Cardiovascular Event Risk A Prospective Study of 3 Population-Based Cohorts
Peter Würtz,Aki S. Havulinna,Pasi Soininen,Tuulia Tynkkynen,David Prieto-Merino,Therese Tillin,Anahita Ghorbani,Anna Artati,Qin Wang,Mika Tiainen,Antti J. Kangas,Johannes Kettunen,Jari Kaikkonen,Vera Mikkilä,Antti Jula,Mika Kähönen,Terho Lehtimäki,Debbie A Lawlor,Tom R. Gaunt,Alun D. Hughes,Naveed Sattar,Thomas Illig,Jerzy Adamski,Thomas J. Wang,Markus Perola,Samuli Ripatti,Ramachandran S. Vasan,Olli T. Raitakari,Robert E. Gerszten,Juan-Pablo Casas,Nish Chaturvedi,Mika Ala-Korpela,Veikko Salomaa +32 more
TL;DR: The value of high-throughput metabolomics for biomarker discovery and improved risk assessment is substantiated and the value of net reclassification was particularly improved for persons in the 5% to 10% risk range.
Journal ArticleDOI
Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development
Jared R. Mayers,Chen Wu,Chen Wu,Clary B. Clish,Peter Kraft,Margaret E. Torrence,Brian P. Fiske,Chen Yuan,Ying Bao,Mary K. Townsend,Shelley S. Tworoger,Shawn M. Davidson,Thales Papagiannakopoulos,Annan Yang,Talya L. Dayton,Shuji Ogino,Shuji Ogino,Meir J. Stampfer,Edward Giovannucci,Zhi Rong Qian,Douglas A. Rubinson,Jing Ma,Howard D. Sesso,John Michael Gaziano,John Michael Gaziano,Barbara B. Cochrane,Simin Liu,Jean Wactawski-Wende,JoAnn E. Manson,Michael Pollak,Alec C. Kimmelman,Amanda Souza,Kerry A. Pierce,Thomas J. Wang,Robert E. Gerszten,Charles S. Fuchs,Charles S. Fuchs,Matthew G. Vander Heiden,Brian M. Wolpin,Brian M. Wolpin +39 more
TL;DR: It is suggested that increased whole-body protein breakdown is an early event in development of PDAC, and elevated plasma levels of branched-chain amino acids (BCAAs) are associated with a greater than twofold increased risk of future pancreatic cancer diagnosis.
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