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Appears in Collections:Computing Science and Mathematics Journal Articles
Peer Review Status: Refereed
Title: Heterogeneity in phenotype, disease progression and drug response in type 2 diabetes
Author(s): Nair, Anand Thakarakkattil Narayanan
Wesolowska-Andersen, Agata
Brorsson, Caroline
Rajendrakumar, Aravind Lathika
Hapca, Simona
Gan, Sushrima
Dawed, Adem Y
Donnelly, Louise A
McCrimmon, Rory
Doney, Alex S F
Palmer, Colin N A
Viswanathan, Mohan
Anjana, Ranjit M
Hattersley, Andrew T
Dennis, John M
Pearson, Ewan R
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Keywords: Type 2 diabetes
Issue Date: May-2022
Date Deposited: 28-Mar-2022
Citation: Nair ATN, Wesolowska-Andersen A, Brorsson C, Rajendrakumar AL, Hapca S, Gan S, Dawed AY, Donnelly LA, McCrimmon R, Doney ASF, Palmer CNA, Viswanathan M, Anjana RM, Hattersley AT, Dennis JM & Pearson ER (2022) Heterogeneity in phenotype, disease progression and drug response in type 2 diabetes. Nature Medicine, 28, pp. 982-988.
Abstract: Type 2 diabetes (T2D) is a complex chronic disease characterized by considerable phenotypic heterogeneity. In this study, we applied a reverse graph embedding method to routinely collected data from 23,137 Scottish patients with newly diagnosed diabetes to visualize this heterogeneity and used partitioned diabetes polygenic risk scores to gain insight into the underlying biological processes. Overlaying risk of progression to outcomes of insulin requirement, chronic kidney disease, referable diabetic retinopathy and major adverse cardiovascular events, we show how these risks differ by patient phenotype. For example, patients at risk of retinopathy are phenotypically different from those at risk of cardiovascular events. We replicated our findings in the UK Biobank and the ADOPT clinical trial, also showing that the pattern of diabetes drug monotherapy response differs for different drugs. Overall, our analysis highlights how, in a European population, underlying phenotypic variation drives T2D onset and affects subsequent diabetes outcomes and drug response, demonstrating the need to incorporate these factors into personalized treatment approaches for the management of T2D.
DOI Link: 10.1038/s41591-022-01790-7
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