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Wagner, R. ; Heni, M. ; Tabak, A.G.* ; Machann, J. ; Randrianarisoa, E. ; Hrabě de Angelis, M. ; Birkenfeld, A.L. ; Stefan, N. ; Peter, A. ; Häring, H.-U. ; Fritsche, A. ; Schick, F.*

Pathophysiology-based subphenotyping of individuals at elevated risk for type 2 diabetes.

Nat. Med. 27, 49-57 (2021)
Postprint Forschungsdaten DOI PMC
Open Access Green
The state of intermediate hyperglycemia is indicative of elevated risk of developing type 2 diabetes1. However, the current definition of prediabetes neither reflects subphenotypes of pathophysiology of type 2 diabetes nor is predictive of future metabolic trajectories. We used partitioning on variables derived from oral glucose tolerance tests, MRI-measured body fat distribution, liver fat content and genetic risk in a cohort of extensively phenotyped individuals who are at increased risk for type 2 diabetes2,3 to identify six distinct clusters of subphenotypes. Three of the identified subphenotypes have increased glycemia (clusters 3, 5 and 6), but only individuals in clusters 5 and 3 have imminent diabetes risks. By contrast, those in cluster 6 have moderate risk of type 2 diabetes, but an increased risk of kidney disease and all-cause mortality. Findings were replicated in an independent cohort using simple anthropomorphic and glycemic constructs4. This proof-of-concept study demonstrates that pathophysiological heterogeneity exists before diagnosis of type 2 diabetes and highlights a group of individuals who have an increased risk of complications without rapid progression to overt type 2 diabetes.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Intima-media Thickness; Fatty Liver-disease; Insulin-resistance; Glucose-tolerance; Adipose-tissue; Sensitivity; Association; Smoking; Obesity; Microalbuminuria
Sprache englisch
Veröffentlichungsjahr 2021
HGF-Berichtsjahr 2021
ISSN (print) / ISBN 1078-8956
e-ISSN 1546-170X
Zeitschrift Nature medicine
Quellenangaben Band: 27, Heft: 1, Seiten: 49-57 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York, NY
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
Institute of Experimental Genetics (IEG)
POF Topic(s) 90000 - German Center for Diabetes Research
30201 - Metabolic Health
Forschungsfeld(er) Helmholtz Diabetes Center
Genetics and Epidemiology
PSP-Element(e) G-502400-001
G-500600-001
Förderungen Federal Ministry of Education and Research (BMBF)
state of Baden-Wurttemberg
UK Medical Research Council
British Heart Foundation
US National Institutes of Health
DOI 10.1038/s41591-020-1116-9
WOS ID WOS:000604849400004
Scopus ID 85098795850
PubMed ID 33398163
Erfassungsdatum 2021-02-08
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