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

Shaza B. Zaghlool, Anna Halama, Nisha Stephan, Valborg Gudmundsdottir, Vilmundur Gudnason, Lori L. Jennings, Manonanthini Thangam, Emma Ahlqvist, Rayaz A. Malik, Omar M. E. Albagha, Abdul Badi Abou‑Samra and Karsten Suhre ()
Additional contact information
Shaza B. Zaghlool: Weill Cornell Medicine-Qatar
Anna Halama: Weill Cornell Medicine-Qatar
Nisha Stephan: Weill Cornell Medicine-Qatar
Valborg Gudmundsdottir: University of Iceland
Vilmundur Gudnason: University of Iceland
Lori L. Jennings: Novartis Institutes for Biomedical Research
Manonanthini Thangam: Lund University
Emma Ahlqvist: Lund University
Rayaz A. Malik: Weill Cornell Medicine-Qatar
Omar M. E. Albagha: Hamad Bin Khalifa University, Education City
Abdul Badi Abou‑Samra: Hamad Medical Corporation
Karsten Suhre: Weill Cornell Medicine-Qatar

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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 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.

Date: 2022
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DOI: 10.1038/s41467-022-34754-z

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