Press Release

04.01.2021

Pathophysiology-based subphenotyping of people with prediabetes

The  state of intermediate  hyperglycemia is indicative of elevated risk of developing type 2 diabetes. However, the current definition of  prediabetes  neither reflects  subphenotypes  of the pathophysiology of type 2 diabetes nor is it predictive for 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 diabetes 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 a 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 constructs.
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.

04.01.2021; Nature Medicine, Volume 27, pages49–57(2021), PMID: 33398163