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

Nat. Med. 27, 49-57 (2021)
Verlagsversion Postprint Forschungsdaten DOI
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
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
Förderungen Federal Ministry of Education and Research (BMBF)
state of Baden-Wurttemberg
UK Medical Research Council
British Heart Foundation
US National Institutes of Health