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Dimethylguanidino valeric acid is a marker of liver fat and predicts diabetes.

ABSTRACT: Unbiased, "nontargeted" metabolite profiling techniques hold considerable promise for biomarker and pathway discovery, in spite of the lack of successful applications to human disease. By integrating nontargeted metabolomics, genetics, and detailed human phenotyping, we identified dimethylguanidino valeric acid (DMGV) as an independent biomarker of CT-defined nonalcoholic fatty liver disease (NAFLD) in the offspring cohort of the Framingham Heart Study (FHS) participants. We verified the relationship between DMGV and early hepatic pathology. Specifically, plasma DMGV levels were correlated with biopsy-proven nonalcoholic steatohepatitis (NASH) in a hospital cohort of individuals undergoing gastric bypass surgery, and DMGV levels fell in parallel with improvements in post-procedure cardiometabolic parameters. Further, baseline DMGV levels independently predicted future diabetes up to 12 years before disease onset in 3 distinct human cohorts. Finally, we provide all metabolite peak data consisting of known and unidentified peaks, genetics, and key metabolic parameters as a publicly available resource for investigations in cardiometabolic diseases.

SUBMITTER: O'Sullivan JF

PROVIDER: S-EPMC5707166 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Dimethylguanidino valeric acid is a marker of liver fat and predicts diabetes.

O'Sullivan John F JF Morningstar Jordan E JE Yang Qiong Q Zheng Baohui B Gao Yan Y Jeanfavre Sarah S Scott Justin J Fernandez Celine C Zheng Hui H O'Connor Sean S Cohen Paul P Vasan Ramachandran S RS Long Michelle T MT Wilson James G JG Melander Olle O Wang Thomas J TJ Fox Caroline C Peterson Randall T RT Clish Clary B CB Corey Kathleen E KE Gerszten Robert E RE

The Journal of clinical investigation 20171030 12

Unbiased, "nontargeted" metabolite profiling techniques hold considerable promise for biomarker and pathway discovery, in spite of the lack of successful applications to human disease. By integrating nontargeted metabolomics, genetics, and detailed human phenotyping, we identified dimethylguanidino valeric acid (DMGV) as an independent biomarker of CT-defined nonalcoholic fatty liver disease (NAFLD) in the offspring cohort of the Framingham Heart Study (FHS) participants. We verified the relatio ...[more]

PMID: 29083323

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Dimethylguanidino valeric acid is a marker of liver fat and predicts diabetes.

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Dimethylguanidino valeric acid is a marker of liver fat and predicts diabetes.

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