Pathophysiology-based subphenotyping of individuals at elevated risk for type 2 diabetes
- 4 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 27 (1), 49-57
- https://doi.org/10.1038/s41591-020-1116-9
Abstract
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.Keywords
Funding Information
- Bundesministerium für Bildung und Forschung (01GI0925, 01GI0925, 01GI0925)
- Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg (32-5400/58/2, 32-5400/58/2, 32-5400/58/2)
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