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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. [extern]*

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

Nat. Med. 27, 49-57 (2021)
Postprint 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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Intima-media Thickness; Fatty Liver-disease; Insulin-resistance; Glucose-tolerance; Adipose-tissue; Sensitivity; Association; Smoking; Obesity; Microalbuminuria
ISSN (print) / ISBN 1078-8956
e-ISSN 1546-170X
Journal Nature medicine
Quellenangaben Volume: 27, Issue: 1, Pages: 49-57 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)
Institute of Experimental Genetics (IEG)
Grants Federal Ministry of Education and Research (BMBF)
state of Baden-Wurttemberg
UK Medical Research Council
British Heart Foundation
US National Institutes of Health