Altered blood gene expression in the obesity-related type 2 diabetes cluster may be causally involved in lipid metabolism: a Mendelian randomisation study – published online 24/02/2023

Juliette A. de Klerk, Joline W. J. Beulens, Hailiang Mei, Roel Bijkerk, Anton Jan van Zonneveld, Robert W. Koivula, Petra J. M. Elders, Leen M. ’t Hart, Roderick C. Slieker

Individuals with diabetes are a heterogenous group and therefore further stratification is key. It has previously been shown that individuals with type 2 diabetes can be organised into five clusters based on five clinical variables: age, HbA_1c, BMI, C-peptide level and HDL-cholesterol level. While clusters differ in terms of clinical outcomes, the differences at the molecular level are largely unclear. In this issue, de Klerk et al (https://doi.org/10.1007/s00125-023-05886-8) compare whole blood gene expression profiles between the different clusters of people with diabetes. The authors show that relatively young people with a high BMI have an altered blood transcriptome profile compared with the other clusters. Using Mendelian randomisation, they demonstrate that the differentially expressed mRNAs may have a causal effect on multiple traits, including anthropometric characteristics and lipid metabolism. The authors conclude that the clusters may help to further stratify people with diabetes, highlighting the different underlying pathophysiologies and providing a more holistic view of type 2 diabetes.

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