Wagner, R;
Heni, M;
Tabák, AG;
Machann, J;
Schick, F;
Randrianarisoa, E;
Hrabě de Angelis, M;
... Fritsche, A; + view all
(2021)
Pathophysiology-based subphenotyping of individuals at elevated risk for type 2 diabetes.
Nature Medicine
, 27
pp. 49-57.
10.1038/s41591-020-1116-9.
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Abstract
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 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 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 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.
| Type: | Article |
|---|---|
| Title: | Pathophysiology-based subphenotyping of individuals at elevated risk for type 2 diabetes |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41591-020-1116-9 |
| Publisher version: | https://doi.org/10.1038/s41591-020-1116-9 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Diabetes complications, Endocrinology, Metabolic syndrome, Type 2 diabetes |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10119132 |
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