Distinct molecular signatures of clinical clusters in people with Type 2 diabetes: an IMIRHAPSODY study.
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2021-08-10
Date Acceptance
2021-08-01
Citation
Diabetes, 2021, 70 (11), pp.2683-2693
ISSN
0012-1797
Publisher
American Diabetes Association
Start Page
2683
End Page
2693
Journal / Book Title
Diabetes
Volume
70
Issue
11
Copyright Statement
© 2021 by the American Diabetes Association https://www.diabetesjournals.org/content/license
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license.
Sponsor
MRC Programme Grant
Wellcome Trust
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/34376475
PII: db20-1281
Grant Number
MR/R022259/1
212625/Z/18/Z
Subjects
Endocrinology & Metabolism
11 Medical and Health Sciences
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2021-08-10