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@article{Slieker:2021:10.2337/db20-1281,
author = {Slieker, RC and Donnelly, LA and Fitipaldi, H and Bouland, GA and Giordano, GN and Åkerlund, M and Gerl, MJ and Ahlqvist, E and Ali, A and Dragan, I and Elders, P and Festa, A and Hansen, MK and van, der Heijden AA and Aly, DM and Kim, M and Kuznetsov, D and Mehl, F and Klose, C and Simons, K and Pavo, I and Pullen, TJ and Suvitaival, T and Wretlind, A and Rossing, P and Lyssenko, V and Quigley, CL and Groop, L and Thorens, B and Franks, PW and Ibberson, M and Rutter, GA and Beulens, JW and 't, Hart LM and Pearson, ER},
doi = {10.2337/db20-1281},
journal = {Diabetes},
pages = {2683--2693},
title = {Distinct molecular signatures of clinical clusters in people with Type 2 diabetes: an IMIRHAPSODY study.},
url = {http://dx.doi.org/10.2337/db20-1281},
volume = {70},
year = {2021}
}

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TY  - JOUR
AB  - Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity a previous study clustered people with diabetes into five diabetes subtypes. The aim of the current study is to investigate the aetiology 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=12828), metabolomic- (N=2945), lipidomic- (N=2593) and proteomic (N=1170) data were obtained in plasma. In each datatype each cluster was compared with the other four clusters as the reference. The insulin resistant cluster showed the most distinct molecular signature, with higher BCAAs, DAG and TAG levels and aberrant protein levels in plasma enriched for proteins in the intracellular PI3K/Akt pathway. The obese cluster showed higher cytokines. A subset of the mild diabetes cluster with high HDL showed the most beneficial molecular profile with opposite effects to those seen in the insulin resistant cluster. This study showed 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.
AU  - Slieker,RC
AU  - Donnelly,LA
AU  - Fitipaldi,H
AU  - Bouland,GA
AU  - Giordano,GN
AU  - Åkerlund,M
AU  - Gerl,MJ
AU  - Ahlqvist,E
AU  - Ali,A
AU  - Dragan,I
AU  - Elders,P
AU  - Festa,A
AU  - Hansen,MK
AU  - van,der Heijden AA
AU  - Aly,DM
AU  - Kim,M
AU  - Kuznetsov,D
AU  - Mehl,F
AU  - Klose,C
AU  - Simons,K
AU  - Pavo,I
AU  - Pullen,TJ
AU  - Suvitaival,T
AU  - Wretlind,A
AU  - Rossing,P
AU  - Lyssenko,V
AU  - Quigley,CL
AU  - Groop,L
AU  - Thorens,B
AU  - Franks,PW
AU  - Ibberson,M
AU  - Rutter,GA
AU  - Beulens,JW
AU  - 't,Hart LM
AU  - Pearson,ER
DO  - 10.2337/db20-1281
EP  - 2693
PY  - 2021///
SN  - 0012-1797
SP  - 2683
TI  - Distinct molecular signatures of clinical clusters in people with Type 2 diabetes: an IMIRHAPSODY study.
T2  - Diabetes
UR  - http://dx.doi.org/10.2337/db20-1281
UR  - https://www.ncbi.nlm.nih.gov/pubmed/34376475
UR  - https://diabetes.diabetesjournals.org/content/early/2021/08/09/db20-1281
UR  - http://hdl.handle.net/10044/1/91436
VL  - 70
ER  -

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