Blood Monocyte Phenotype Is A Marker of Cardiovascular Risk in Type 2 Diabetes.
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Julla Jean-Baptiste, Girard Diane, Diedisheim Marc, Saulnier Pierre-Jean, Tran Vuong Bao, Blériot Camille, Carcarino Elena, De Keizer Joe, Orliaguet Lucie, Nemazanyy Ivan, Potier Charline, Khider Kennan, Tonui Dorothy Chepngenoh, Ejlalmanesh Tina, Ballaire Raphaelle, Mambu Mambueni Hendrick, Germain Stéphane, Gaborit Bénédicte, Vidal-Trécan Tiphaine, Riveline Jean-Pierre, Garchon Henri-Jean, Fenaille François, Lemoine Sophie, Carlier Aurélie, Castelli Florence, Potier Louis, Masson David, Roussel Ronan, Vandiedonck Claire, Hadjadj Samy, Alzaid Fawaz, Gautier Jean-François, Venteclef Nicolas
Аннотация
METHODS: We investigated the relationship between circulating monocytes and cardiovascular risk progression in people with T2D, using phenotypic, transcriptomic, and metabolomic analyses. cardiovascular risk progression was estimated with coronary artery calcium score in a cohort of 672 people with T2D.
RESULTS: Coronary artery calcium score was positively correlated with blood monocyte count and frequency of the classical monocyte subtype. Unsupervised k-means clustering based on monocyte subtype profiles revealed 3 main endotypes of people with T2D at varying risk of cardiovascular events. These observations were confirmed in a validation cohort of 279 T2D participants. The predictive association between monocyte count and major adverse cardiovascular events was validated through an independent prospective cohort of 757 patients with T2D. Integration of monocyte transcriptome analyses and plasma metabolomes showed a disruption of mitochondrial pathways (tricarboxylic acid cycle, oxidative phosphorylation pathway) that underlined a proatherogenic phenotype.
CONCLUSIONS: In this study, we provide evidence that frequency and monocyte phenotypic profile are closely linked to cardiovascular risk in patients with T2D. The assessment of monocyte frequency and count is a valuable predictive marker for risk of cardiovascular events in patients with T2D.
REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04353869.