Distinct Molecular Signatures of Clinical Clusters in People With Type 2 Diabetes: An IMI-RHAPSODY Study.

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Etat: Public
Version: de l'auteur⸱e
Licence: Non spécifiée
ID Serval
serval:BIB_A3ADFE199CED
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Distinct Molecular Signatures of Clinical Clusters in People With Type 2 Diabetes: An IMI-RHAPSODY Study.
Périodique
Diabetes
Auteur⸱e⸱s
Slieker R.C., Donnelly L.A., Fitipaldi H., Bouland G.A., Giordano G.N., Åkerlund M., Gerl M.J., Ahlqvist E., Ali A., Dragan I., Elders P., Festa A., Hansen M.K., van der Heijden A.A., Mansour Aly D., Kim M., Kuznetsov D., Mehl F., Klose C., Simons K., Pavo I., Pullen T.J., Suvitaival T., Wretlind A., Rossing P., Lyssenko V., Legido Quigley C., Groop L., Thorens B., Franks P.W., Ibberson M., Rutter G.A., Beulens JWJ, 't Hart L.M., Pearson E.R.
ISSN
1939-327X (Electronic)
ISSN-L
0012-1797
Statut éditorial
Publié
Date de publication
11/2021
Peer-reviewed
Oui
Volume
70
Numéro
11
Pages
2683-2693
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity, investigators of a previous study clustered people with diabetes according to five diabetes subtypes. The aim of the current study is to investigate the etiology of these clusters by comparing their molecular signatures. In three independent cohorts, in total 15,940 individuals were clustered based on five clinical characteristics. In a subset, genetic (N = 12,828), metabolomic (N = 2,945), lipidomic (N = 2,593), and proteomic (N = 1,170) data were obtained in plasma. For each data type, each cluster was compared with the other four clusters as the reference. The insulin-resistant cluster showed the most distinct molecular signature, with higher branched-chain amino acid, diacylglycerol, and triacylglycerol levels and aberrant protein levels in plasma were enriched for proteins in the intracellular PI3K/Akt pathway. The obese cluster showed higher levels of cytokines. The mild diabetes cluster with high HDL showed the most beneficial molecular profile with effects opposite of those seen in the insulin-resistant cluster. This study shows that clustering people with type 2 diabetes can identify underlying molecular mechanisms related to pancreatic islets, liver, and adipose tissue metabolism. This provides novel biological insights into the diverse aetiological processes that would not be evident when type 2 diabetes is viewed as a homogeneous disease.
Mots-clé
Cluster Analysis, Cohort Studies, Cross-Sectional Studies, Diabetes Mellitus, Type 2/metabolism, Humans, Insulin Resistance
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/08/2021 12:28
Dernière modification de la notice
12/03/2022 6:29
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