Imperial College London
Alternate

Professor Neil Poulter

Faculty of Medicine, School of Public Health

Professor of Preventive Cardiovascular Medicine.
 
 
 
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Contact

 

+44 (0)20 7594 3446n.poulter

 
 
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Assistant

 

Mrs Ranjit Rayat +44 (0)20 7594 3445

 
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Location

 

55Stadium HouseWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Welsh:2018:10.1007/s00125-018-4619-x,
author = {Welsh, P and Rankin, N and Li, Q and Mark, PB and Würtz, P and Ala-Korpela, M and Marre, M and Poulter, N and Hamet, P and Chalmers, J and Woodward, M and Sattar, N},
doi = {10.1007/s00125-018-4619-x},
journal = {Diabetologia},
pages = {1581--1591},
title = {Circulating amino acids and the risk of macrovascular, microvascular and mortality outcomes in individuals with type 2 diabetes: results from the ADVANCE trial},
url = {http://dx.doi.org/10.1007/s00125-018-4619-x},
volume = {61},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - AIMS/HYPOTHESES: We aimed to quantify the association of individual circulating amino acids with macrovascular disease, microvascular disease and all-cause mortality in individuals with type 2 diabetes. METHODS: We performed a case-cohort study (N = 3587), including 655 macrovascular events, 342 microvascular events (new or worsening nephropathy or retinopathy) and 632 all-cause mortality events during follow-up, in a secondary analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study. For this study, phenylalanine, isoleucine, glutamine, leucine, alanine, tyrosine, histidine and valine were measured in stored plasma samples by proton NMR metabolomics. Hazard ratios were modelled per SD increase in each amino acid. RESULTS: In models investigating associations and potential mechanisms, after adjusting for age, sex and randomised treatment, phenylalanine was positively, and histidine inversely, associated with macrovascular disease risk. These associations were attenuated to the null on further adjustment for extended classical risk factors (including eGFR and urinary albumin/creatinine ratio). After adjustment for extended classical risk factors, higher tyrosine and alanine levels were associated with decreased risk of microvascular disease (HR 0.78; 95% CI 0.67, 0.91 and HR 0.86; 95% CI 0.76, 0.98, respectively). Higher leucine (HR 0.79; 95% CI 0.69, 0.90), histidine (HR 0.89; 95% CI 0.81, 0.99) and valine (HR 0.79; 95% CI 0.70, 0.88) levels were associated with lower risk of mortality. Investigating the predictive ability of amino acids, addition of all amino acids to a risk score modestly improved classification of participants for macrovascular (continuous net reclassification index [NRI] +35.5%, p < 0.001) and microvascular events (continuous NRI +14.4%, p = 0.012). CONCLUSIONS/INTERPRETATION: We report distinct associations between circulat
AU  - Welsh,P
AU  - Rankin,N
AU  - Li,Q
AU  - Mark,PB
AU  - Würtz,P
AU  - Ala-Korpela,M
AU  - Marre,M
AU  - Poulter,N
AU  - Hamet,P
AU  - Chalmers,J
AU  - Woodward,M
AU  - Sattar,N
DO  - 10.1007/s00125-018-4619-x
EP  - 1591
PY  - 2018///
SN  - 0012-186X
SP  - 1581
TI  - Circulating amino acids and the risk of macrovascular, microvascular and mortality outcomes in individuals with type 2 diabetes: results from the ADVANCE trial
T2  - Diabetologia
UR  - http://dx.doi.org/10.1007/s00125-018-4619-x
UR  - https://www.ncbi.nlm.nih.gov/pubmed/29728717
UR  - http://hdl.handle.net/10044/1/61426
VL  - 61
ER  -
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