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Metabolic and proteomic signatures of type 2 diabetes subtypes in an Arab population

Zaghlool, Shaza B. ; Halama, Anna ; Stephan, Nisha ; Gudmundsdottir, Valborg ; Gudnason, Vilmundur ; Jennings, Lori L. ; Thangam, Manonanthini LU ; Ahlqvist, Emma LU ; Malik, Rayaz A. and Albagha, Omar M.E. , et al. (2022) In Nature Communications 13(1).
Abstract

Type 2 diabetes (T2D) has a heterogeneous etiology influencing its progression, treatment, and complications. A data driven cluster analysis in European individuals with T2D previously identified four subtypes: severe insulin deficient (SIDD), severe insulin resistant (SIRD), mild obesity-related (MOD), and mild age-related (MARD) diabetes. Here, the clustering approach was applied to individuals with T2D from the Qatar Biobank and validated in an independent set. Cluster-specific signatures of circulating metabolites and proteins were established, revealing subtype-specific molecular mechanisms, including activation of the complement system with features of autoimmune diabetes and reduced 1,5-anhydroglucitol in SIDD, impaired insulin... (More)

Type 2 diabetes (T2D) has a heterogeneous etiology influencing its progression, treatment, and complications. A data driven cluster analysis in European individuals with T2D previously identified four subtypes: severe insulin deficient (SIDD), severe insulin resistant (SIRD), mild obesity-related (MOD), and mild age-related (MARD) diabetes. Here, the clustering approach was applied to individuals with T2D from the Qatar Biobank and validated in an independent set. Cluster-specific signatures of circulating metabolites and proteins were established, revealing subtype-specific molecular mechanisms, including activation of the complement system with features of autoimmune diabetes and reduced 1,5-anhydroglucitol in SIDD, impaired insulin signaling in SIRD, and elevated leptin and fatty acid binding protein levels in MOD. The MARD cluster was the healthiest with metabolomic and proteomic profiles most similar to the controls. We have translated the T2D subtypes to an Arab population and identified distinct molecular signatures to further our understanding of the etiology of these subtypes.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ANDIS, diabetes
in
Nature Communications
volume
13
issue
1
article number
7121
publisher
Nature Publishing Group
external identifiers
  • pmid:36402758
  • scopus:85142267290
ISSN
2041-1723
DOI
10.1038/s41467-022-34754-z
language
English
LU publication?
yes
id
ae28b26f-8655-42b9-801d-0310dd3875ad
date added to LUP
2022-12-29 15:21:22
date last changed
2025-04-06 08:00:49
@article{ae28b26f-8655-42b9-801d-0310dd3875ad,
  abstract     = {{<p>Type 2 diabetes (T2D) has a heterogeneous etiology influencing its progression, treatment, and complications. A data driven cluster analysis in European individuals with T2D previously identified four subtypes: severe insulin deficient (SIDD), severe insulin resistant (SIRD), mild obesity-related (MOD), and mild age-related (MARD) diabetes. Here, the clustering approach was applied to individuals with T2D from the Qatar Biobank and validated in an independent set. Cluster-specific signatures of circulating metabolites and proteins were established, revealing subtype-specific molecular mechanisms, including activation of the complement system with features of autoimmune diabetes and reduced 1,5-anhydroglucitol in SIDD, impaired insulin signaling in SIRD, and elevated leptin and fatty acid binding protein levels in MOD. The MARD cluster was the healthiest with metabolomic and proteomic profiles most similar to the controls. We have translated the T2D subtypes to an Arab population and identified distinct molecular signatures to further our understanding of the etiology of these subtypes.</p>}},
  author       = {{Zaghlool, Shaza B. and Halama, Anna and Stephan, Nisha and Gudmundsdottir, Valborg and Gudnason, Vilmundur and Jennings, Lori L. and Thangam, Manonanthini and Ahlqvist, Emma and Malik, Rayaz A. and Albagha, Omar M.E. and Abou‑Samra, Abdul Badi and Suhre, Karsten}},
  issn         = {{2041-1723}},
  keywords     = {{ANDIS; diabetes}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Metabolic and proteomic signatures of type 2 diabetes subtypes in an Arab population}},
  url          = {{http://dx.doi.org/10.1038/s41467-022-34754-z}},
  doi          = {{10.1038/s41467-022-34754-z}},
  volume       = {{13}},
  year         = {{2022}},
}