Applying metabolomics to cardiometabolic intervention studies and trials: past experiences and a roadmap for the future

Rankin, N. J. , Preiss, D. , Welsh, P. and Sattar, N. (2016) Applying metabolomics to cardiometabolic intervention studies and trials: past experiences and a roadmap for the future. International Journal of Epidemiology, 45(5), pp. 1351-1371. (doi:10.1093/ije/dyw271) (PMID:27789671) (PMCID:PMC5100629)

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Abstract

Metabolomics and lipidomics are emerging methods for detailed phenotyping of small molecules in samples. It is hoped that such data will: (i) enhance baseline prediction of patient response to pharmacotherapies (beneficial or adverse); (ii) reveal changes in metabolites shortly after initiation of therapy that may predict patient response, including adverse effects, before routine biomarkers are altered; and( iii) give new insights into mechanisms of drug action, particularly where the results of a trial of a new agent were unexpected, and thus help future drug development. In these ways, metabolomics could enhance research findings from intervention studies. This narrative review provides an overview of metabolomics and lipidomics in early clinical intervention studies for investigation of mechanisms of drug action and prediction of drug response (both desired and undesired). We highlight early examples from drug intervention studies associated with cardiometabolic disease. Despite the strengths of such studies, particularly the use of state-of-the-art technologies and advanced statistical methods, currently published studies in the metabolomics arena are largely underpowered and should be considered as hypothesis-generating. In order for metabolomics to meaningfully improve stratified medicine approaches to patient treatment, there is a need for higher quality studies, with better exploitation of biobanks from randomized clinical trials i.e. with large sample size, adjudicated outcomes, standardized procedures, validation cohorts, comparison witth routine biochemistry and both active and control/placebo arms. On the basis of this review, and based on our research experience using clinically established biomarkers, we propose steps to more speedily advance this area of research towards potential clinical impact.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Welsh, Dr Paul and Rankin, Dr Naomi and Preiss, Dr David and Sattar, Professor Naveed
Authors: Rankin, N. J., Preiss, D., Welsh, P., and Sattar, N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:International Journal of Epidemiology
Publisher:Oxford University Press
ISSN:0300-5771
ISSN (Online):1464-3685
Published Online:27 October 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in International Journal of Epidemiology 2016
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
629851The UPBEAT RCT mother-child study. Stratifying and treating obese pregnant women to prevent adverse pregnancy, perinatal and longer term outcomesPaul WelshMedical Research Council (MRC)MR/L002477/1RI CARDIOVASCULAR & MEDICAL SCIENCES
468871Effect of metformin on progression of carotid atherosclerosis in non-diabetic patients with CHD optimally treated with conventional risk reducing agentsNaveed SattarScottish Executive Health Department (SEHHD-CSO)CZB/4/613RI CARDIOVASCULAR & MEDICAL SCIENCES
594271Integrated Health - Polyomics and Systems Biomedicine (ISSF Bid)Anna DominiczakWellcome Trust (WELLCOME)097821/Z/11/ZRI CARDIOVASCULAR & MEDICAL SCIENCES
603151EMIFNaveed SattarEuropean Commission (EC)115372RI CARDIOVASCULAR & MEDICAL SCIENCES
601881HOMAGE: Heart OMics in AGEingChristian DellesEuropean Commission (EC)305507RI CARDIOVASCULAR & MEDICAL SCIENCES
621401Assessing the predictive value of quantitative high-throughput NMR metabolomic analysis for CVD events in a major study of diabetes: ADVANCEPaul WelshChest, Heart & Stroke, Scotland (CHSS)R13/A149RI CARDIOVASCULAR & MEDICAL SCIENCES