1 research outputs found
Distinct 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 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 diseas