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, Karsten Suhre
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...
November 19, 2022: Nature Communications