biostudies-literatureSlieker RCSteno Diabetes Center Copenhagen (SDCC)Medical Research CouncilWellcome TrustNovo Nordisk Fonden2683-2693https://www.ebi.ac.uk/biostudies/studies/S-EPMC8564413biostudies-literatureUnknown70(11)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 (<i>N</i> = 12,828), metabolomic (<i>N</i> = 2,945), lipidomic (<i>N</i> = 2,593), and proteomic (<i>N</i> = 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 brancDiabetesDistinct Molecular Signatures of Clinical Clusters in People With Type 2 Diabetes: An IMI-RHAPSODY Study.PMC8564413MR/R022259/1212625/Z/18/ZSDCC 3.A Complications102820/Z/13/ZSDCC 3.C. Sys MedMR/L020149/1WT098424AIAMR/J0003042/1NNF18OC0034440Franks PWElders PLyssenko VSuvitaival TRossing PMehl FBeulens JWJKim MKuznetsov DKlose CFitipaldi HPearson ERAli AFesta ADonnelly LADragan IBouland GAWretlind APavo IGroop Lvan der Heijden AA't Hart LMHansen MKGerl MJAhlqvist EAkerlund MGiordano GNPullen TJIbberson MSlieker RCSimons KRutter GAThorens BMansour Aly DLegido Quigley CfalseDistinct Molecular Signatures of Clinical Clusters in People With Type 2 Diabetes: An IMI-RHAPSODY Study.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 (<i>N</i> = 12,828), metabolomic (<i>N</i> = 2,945), lipidomic (<i>N</i> = 2,593), and proteomic (<i>N</i> = 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 branc2021-01-01T00:00:00Z2021 Nov2025-06-01T12:26:01.352Z2022-02-11T12:56:52.089ZS-EPMC85644133437647510.2337/db20-1281