. 2024 Jan 19;134(2):189-202.

doi: 10.1161/CIRCRESAHA.123.322757. Epub 2023 Dec 28.

Blood Monocyte Phenotype Is A Marker of Cardiovascular Risk in Type 2 Diabetes

Jean-Baptiste Julla^#^{1

2

3

4}, Diane Girard^#^{1

2

3}, Marc Diedisheim^{1

2

3

5}, Pierre-Jean Saulnier⁶, Bao Tran Vuong^{1

2

3}, Camille Blériot^{1

2

3}, Elena Carcarino^{1

2

3}, Joe De Keizer⁷, Lucie Orliaguet^{1

2

3}, Ivan Nemazanyy¹, Charline Potier^{1

2

3}, Kennan Khider^{1

2

3}, Dorothy Chepngenoh Tonui^{1

2

3}, Tina Ejlalmanesh^{1

2

3}, Raphaelle Ballaire^{1

2

3}, Hendrick Mambu Mambueni⁸, Stéphane Germain⁹, Bénédicte Gaborit^{10

11}, Tiphaine Vidal-Trécan^{3

4}, Jean-Pierre Riveline^{1

2

3

4}, Henri-Jean Garchon⁸, François Fenaille¹², Sophie Lemoine¹³, Aurélie Carlier¹⁴, Florence Castelli¹², Louis Potier^{1

2

3

14}, David Masson^{15

16

17

18}, Ronan Roussel^{1

2

3

14}, Claire Vandiedonck^{1

2

3}, Samy Hadjadj⁷, Fawaz Alzaid^{1

2

3

19}, Jean-François Gautier^{1

2

3

4}, Nicolas Venteclef^{1

2

3}

Affiliations

¹ INSERM, Necker Enfants Malades (INEM), INSERM U1151, CNRS UMR 8253, IMMEDIAB Laboratory (J.-B.J., D.G., M.D., B.T.V., C.B., E.C., L.O., I.N., C.P., K.K., D.C.T., T.E., R.B., J.-P.R., L.P., R.R., C.V., F.A., J.-F.G., N.V.), Université Paris Cité, France.
² Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université (J.-B.J., D.G., M.D., B.T.V., C.B., E.C., L.O., C.P., K.K., D.C.T., T.E., R.B., J.-P.R., L.P., R.R., C.V., F.A., J.-F.G., N.V.), Université Paris Cité, France.
³ Diabetes Institute (J.-B.J., D.G., M.D., B.T.V., C.B., E.C., L.O., C.P., K.K., D.C.T., T.E., R.B., T.V.-T., J.-P.R., L.P., R.R., C.V., F.A., J.-F.G., N.V.), Université Paris Cité, France.
⁴ Diabetology, Endocrinology and Nutrition Department, Lariboisière Hospital, Fédération de Diabétologie, France (J.-B.J., T.V.-T., J.-P.R., J.-F.G.).
⁵ Clinique Saint Gatien Alliance (NCT+), Saint-Cyr-sur-Loire, France (M.D.).
⁶ Poitiers Université, CHU Poitiers, INSERM, Centre d'Investigation Clinique CIC1402, Poitiers, France (P.-J.S.).
⁷ Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France (J.D.K., S.H.).
⁸ Genomics platform UFR Simone Veil 1173; U, University of Versailles Paris-Saclay; Inserm UMR 1173 (H.M.M., H.-J.G.).
⁹ Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, Paris, France (S.G.).
¹⁰ C2VN, INRAE, INSERM, Aix Marseille University, Marseille, France (B.G.).
¹¹ Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, AP-HM, Marseille, France (B.G.).
¹² Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (MTS), MetaboHUB, France (F.F., F.C.).
¹³ Genomics core facility, Institut de Biologie de l'ENS (IBENS), Département de biologie, École Normale Supérieure, CNRS, INSERM, Université PSL, Paris, France (S.L.).
¹⁴ Diabetology and Endocrinology Department, Bichat Hospital, Fédération de Diabétologie, France (L.P., A.C., R.R.).
¹⁵ INSERM, LNC UMR1231, Dijon, France (D.M.).
¹⁶ University of Bourgogne and Franche-Comté, LNC UMR1231, Dijon, France (D.M.).
¹⁷ FCS Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France (D.M.).
¹⁸ Plateau Automatisé de Biochimie, Dijon University Hospital, France (D.M.).
¹⁹ Dasman Diabetes Institute, Kuwait (F.A.).

^# Contributed equally.

PMID: 38152893
DOI: 10.1161/CIRCRESAHA.123.322757

Free article

Blood Monocyte Phenotype Is A Marker of Cardiovascular Risk in Type 2 Diabetes

Jean-Baptiste Julla et al. Circ Res. 2024.

Free article

. 2024 Jan 19;134(2):189-202.

doi: 10.1161/CIRCRESAHA.123.322757. Epub 2023 Dec 28.

Authors

Affiliations

¹ INSERM, Necker Enfants Malades (INEM), INSERM U1151, CNRS UMR 8253, IMMEDIAB Laboratory (J.-B.J., D.G., M.D., B.T.V., C.B., E.C., L.O., I.N., C.P., K.K., D.C.T., T.E., R.B., J.-P.R., L.P., R.R., C.V., F.A., J.-F.G., N.V.), Université Paris Cité, France.
² Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université (J.-B.J., D.G., M.D., B.T.V., C.B., E.C., L.O., C.P., K.K., D.C.T., T.E., R.B., J.-P.R., L.P., R.R., C.V., F.A., J.-F.G., N.V.), Université Paris Cité, France.
³ Diabetes Institute (J.-B.J., D.G., M.D., B.T.V., C.B., E.C., L.O., C.P., K.K., D.C.T., T.E., R.B., T.V.-T., J.-P.R., L.P., R.R., C.V., F.A., J.-F.G., N.V.), Université Paris Cité, France.
⁴ Diabetology, Endocrinology and Nutrition Department, Lariboisière Hospital, Fédération de Diabétologie, France (J.-B.J., T.V.-T., J.-P.R., J.-F.G.).
⁵ Clinique Saint Gatien Alliance (NCT+), Saint-Cyr-sur-Loire, France (M.D.).
⁶ Poitiers Université, CHU Poitiers, INSERM, Centre d'Investigation Clinique CIC1402, Poitiers, France (P.-J.S.).
⁷ Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France (J.D.K., S.H.).
⁸ Genomics platform UFR Simone Veil 1173; U, University of Versailles Paris-Saclay; Inserm UMR 1173 (H.M.M., H.-J.G.).
⁹ Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, Paris, France (S.G.).
¹⁰ C2VN, INRAE, INSERM, Aix Marseille University, Marseille, France (B.G.).
¹¹ Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, AP-HM, Marseille, France (B.G.).
¹² Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (MTS), MetaboHUB, France (F.F., F.C.).
¹³ Genomics core facility, Institut de Biologie de l'ENS (IBENS), Département de biologie, École Normale Supérieure, CNRS, INSERM, Université PSL, Paris, France (S.L.).
¹⁴ Diabetology and Endocrinology Department, Bichat Hospital, Fédération de Diabétologie, France (L.P., A.C., R.R.).
¹⁵ INSERM, LNC UMR1231, Dijon, France (D.M.).
¹⁶ University of Bourgogne and Franche-Comté, LNC UMR1231, Dijon, France (D.M.).
¹⁷ FCS Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France (D.M.).
¹⁸ Plateau Automatisé de Biochimie, Dijon University Hospital, France (D.M.).
¹⁹ Dasman Diabetes Institute, Kuwait (F.A.).

^# Contributed equally.

PMID: 38152893
DOI: 10.1161/CIRCRESAHA.123.322757

Abstract

Background: Diabetes is a major risk factor for atherosclerotic cardiovascular diseases with a 2-fold higher risk of cardiovascular events in people with diabetes compared with those without. Circulating monocytes are inflammatory effector cells involved in both type 2 diabetes (T2D) and atherogenesis.

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.

Keywords: cardiovascular risk; inflammation; metabolism; monocytes; transcriptomic.

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Disclosures None.

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Blood Monocyte Phenotype Is A Marker of Cardiovascular Risk in Type 2 Diabetes

Affiliations

Blood Monocyte Phenotype Is A Marker of Cardiovascular Risk in Type 2 Diabetes

Authors

Affiliations

Abstract

Conflict of interest statement

Publication types

MeSH terms

Substances

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Molecular Biology Databases