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

Wagner, Robert ✉; Heni, Martin; Tabák, Adam G. [Tabák, Ádám (belgyógyászat, di...), szerző] Népegészségtani Intézet (SE / AOK / I); Belgyógyászati és Onkológiai Klinika (SE / AOK / K); Machann, Jürgen; Schick, Fritz; Randrianarisoa, Elko; Hrabě, de Angelis Martin; Birkenfeld, Andreas L.; Stefan, Norbert; Peter, Andreas; Häring, Hans-Ulrich; Fritsche, Andreas

Angol nyelvű Szakcikk (Folyóiratcikk) Tudományos
Megjelent: NATURE MEDICINE 1078-8956 1546-170X 27 (1) pp. 49-57 2021
  • SJR Scopus - Biochemistry, Genetics and Molecular Biology (miscellaneous): D1
  • Orvos- és egészségtudomány
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.
Hivatkozás stílusok: IEEEACMAPAChicagoHarvardCSLMásolásNyomtatás
2024-07-23 19:20