Heterogeneity in phenotype, disease progression and drug response in type 2 diabetes.

Autor: Nair ATN; Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK., Wesolowska-Andersen A; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK., Brorsson C; Novo Nordisk Center for Protein Research, University of Copenhagen, Copenhagen, Denmark., Rajendrakumar AL; Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK., Hapca S; Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK., Gan S; Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK., Dawed AY; Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK., Donnelly LA; Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK., McCrimmon R; Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK., Doney ASF; Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK., Palmer CNA; Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK., Mohan V; Madras Diabetes Research Foundation, Chennai, India., Anjana RM; Madras Diabetes Research Foundation, Chennai, India., Hattersley AT; Institute of Biomedical and Clinical Science, Royal Devon and Exeter Hospital, University of Exeter, Exeter, UK., Dennis JM; Institute of Biomedical and Clinical Science, Royal Devon and Exeter Hospital, University of Exeter, Exeter, UK., Pearson ER; Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK. e.z.pearson@dundee.ac.uk.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2022 May; Vol. 28 (5), pp. 982-988. Date of Electronic Publication: 2022 May 09.
DOI: 10.1038/s41591-022-01790-7
Abstrakt: 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.
(© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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