Four groups of type 2 diabetes contribute to the etiological and clinical heterogeneity in newly diagnosed individuals: An IMI DIRECT study
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Authors
Wesolowska-Andersen, A
Brorsson, CA
Bizzotto, R
Mari, A
Tura, A
Koivula, R
Mahajan, A
Vinuela, A
Tajes, JF
Sharma, S
Haid, M
Prehn, C
Artati, A
Hong, MG
Musholt, PB
Kurbasic, A
De Masi, F
Tsirigos, K
Pedersen, HK
Gudmundsdottir, V
Thomas, CE
Banasik, K
Jennison, C
Jones, A
Kennedy, G
Bell, J
Thomas, L
Frost, G
Thomsen, H
Allin, K
Hansen, TH
Vestergaard, H
Hansen, T
Rutters, F
Elders, P
t'Hart, L
Bonnefond, A
Canouil, M
Kokkola, T
Heggie, A
McEvoy, D
Hattersley, A
McDonald, T
Teare, H
Ridderstrale, M
Walker, M
Forgie, I
Giordano, GN
Froguel, P
Pavo, I
Ruetten, H
Pedersen, O
Dermitzakis, E
Franks, PW
Schwenk, JM
Adamski, J
Pearson, E
McCarthy, MI
Brunak, S
Publication Date
2022-01-18Journal Title
Cell Reports Medicine
ISSN
2666-3791
Publisher
Elsevier BV
Volume
3
Issue
1
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Wesolowska-Andersen, A., Brorsson, C., Bizzotto, R., Mari, A., Tura, A., Koivula, R., Mahajan, A., et al. (2022). Four groups of type 2 diabetes contribute to the etiological and clinical heterogeneity in newly diagnosed individuals: An IMI DIRECT study. Cell Reports Medicine, 3 (1) https://doi.org/10.1016/j.xcrm.2021.100477
Abstract
The presentation and underlying pathophysiology of type 2 diabetes (T2D) is complex and heterogeneous. Recent studies attempted to stratify T2D into distinct subgroups using data-driven approaches, but their clinical utility may be limited if categorical representations of complex phenotypes are suboptimal. We apply a soft-clustering (archetype) method to characterize newly diagnosed T2D based on 32 clinical variables. We assign quantitative clustering scores for individuals and investigate the associations with glycemic deterioration, genetic risk scores, circulating omics biomarkers, and phenotypic stability over 36 months. Four archetype profiles represent dysfunction patterns across combinations of T2D etiological processes and correlate with multiple circulating biomarkers. One archetype associated with obesity, insulin resistance, dyslipidemia, and impaired β cell glucose sensitivity corresponds with the fastest disease progression and highest demand for anti-diabetic treatment. We demonstrate that clinical heterogeneity in T2D can be mapped to heterogeneity in individual etiological processes, providing a potential route to personalized treatments.
Keywords
Type 2 diabetes, Disease Progression, Archetypes, Precision Medicine, Patient Stratification, Multi-omics, Patient Clustering, Soft-clustering, Glycaemic Deterioration, Humans, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Risk Factors, Follow-Up Studies, Genomics, Phenotype, Adult, Middle Aged, Female, Male
Sponsorship
Wellcome Trust (098381, 102820/Z/13/Z, 090532 , 106130, 212259 , 098381 , 090532, 106130 , 212259, 203141, 203141)
National Institute for Health Research (NIHR) (NF-SI-0508-10112)
Identifiers
PMC8784706, 35106505
External DOI: https://doi.org/10.1016/j.xcrm.2021.100477
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334703
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