Carrasco-Zanini, Julia;
Pietzner, Maik;
Lindbohm, Joni V;
Wheeler, Eleanor;
Oerton, Erin;
Kerrison, Nicola;
Simpson, Missy;
... Langenberg, Claudia; + view all
(2022)
Proteomic signatures for identification of impaired glucose tolerance.
Nature Medicine
, 28
pp. 2293-2300.
10.1038/s41591-022-02055-z.
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Abstract
The implementation of recommendations for type 2 diabetes (T2D) screening and diagnosis focuses on the measurement of glycated hemoglobin (HbA1c) and fasting glucose. This approach leaves a large number of individuals with isolated impaired glucose tolerance (iIGT), who are only detectable through oral glucose tolerance tests (OGTTs), at risk of diabetes and its severe complications. We applied machine learning to the proteomic profiles of a single fasted sample from 11,546 participants of the Fenland study to test discrimination of iIGT defined using the gold-standard OGTTs. We observed significantly improved discriminative performance by adding only three proteins (RTN4R, CBPM and GHR) to the best clinical model (AUROC = 0.80 (95% confidence interval: 0.79–0.86), P = 0.004), which we validated in an external cohort. Increased plasma levels of these candidate proteins were associated with an increased risk for future T2D in an independent cohort and were also increased in individuals genetically susceptible to impaired glucose homeostasis and T2D. Assessment of a limited number of proteins can identify individuals likely to be missed by current diagnostic strategies and at high risk of T2D and its complications.
| Type: | Article |
|---|---|
| Title: | Proteomic signatures for identification of impaired glucose tolerance |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41591-022-02055-z |
| Publisher version: | https://doi.org/10.1038/s41591-022-02055-z |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, Medicine, Research & Experimental, Research & Experimental Medicine, NEUTROPHIL SERINE PROTEASES, LIFE-STYLE INTERVENTION, HIGH-RISK, TYPE-2, PREVALENCE, DISEASE, A1C, INDIVIDUALS, ASSOCIATION, DYSGLYCEMIA |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry > Mental Health of Older People |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10167383 |
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