Leiden University Scholarly Publications

Persistent URL of this record https://hdl.handle.net/1887/3563988

Documents

In Collections

This item can be found in the following collections:

Wesolowska-Andersen, A.; Brorsson, C.A.; Bizzotto, R.; Mari, A.; Tura, A.; Koivula, R.; ... ; Brunak, S. (2022)

Four groups of type 2 diabetes contribute to the etiological and clinical heterogeneity in newly diagnosed individuals: an IMI DIRECT study

Article / Letter to editor
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 1 beta cell glucose sensitivity corresponds with the fastest disease progression and highest demand for anti-diabetic...Show moreThe 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 1 beta 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.Show less
All authors
Wesolowska-Andersen, A.; Brorsson, C.A.; Bizzotto, R.; Mari, A.; Tura, A.; Koivula, R.; Mahajan, A.; Vinuela, A.; Tajes, J.F.; Sharma, S.; Haid, M.; Prehn, C.; Artati, A.; Hong, M.G.; Musholt, P.B.; Kurbasic, A.; Masi, F. de; Tsirigos, K.; Pedersen, H.K.; Gudmundsdottir, V.; Thomas, C.E.; Banasik, K.; Jennison, C.; Jones, A.; Kennedy, G.; Bell, J.; Thomas, L.; Frost, G.; Thomsen, H.; Allin, K.; Hansen, T.H.; Vestergaard, H.; Hansen, T.; Rutters, F.; Elders, P.; T'Hart, L.; Bonnefond, A.; Canouil, M.; Brage, S.; Kokkola, T.; Heggie, A.; McEvoy, D.; Hattersley, A.; McDonald, T.; Teare, H.; Ridderstrale, M.; Walker, M.; Forgie, I.; Giordano, G.N.; Froguel, P.; Pavo, I.; Ruetten, H.; Pedersen, O.; Dermitzakis, E.; Franks, P.W.; Schwenk, J.M.; Adamski, J.; Pearson, E.; McCarthy, M.I.; Brunak, S.
Date
2022-01-18
Journal
Cell Reports Medicine
Volume
3
Issue
1
DOI
doi:10.1016/j.xcrm.2021.100477
Link
https://www.sciencedirect.com/science/article/pii/S2666379121003499?via%...