SGLT2 Inhibition with Empagliflozin Increases Circulating Provascular Progenitor Cells in People with Type 2 Diabetes Mellitus

David A Hess; Daniella C Terenzi; Justin Z Trac; Adrian Quan; Tamique Mason; Mohammed Al-Omran; Deepak L Bhatt; Natasha Dhingra; Ori D Rotstein; Lawrence A Leiter; Bernard Zinman; Sandra Sabongui; Andrew T Yan; Hwee Teoh; C David Mazer; Kim A Connelly; Subodh Verma

doi:10.1016/j.cmet.2019.08.015

SGLT2 Inhibition with Empagliflozin Increases Circulating Provascular Progenitor Cells in People with Type 2 Diabetes Mellitus

Cell Metab. 2019 Oct 1;30(4):609-613. doi: 10.1016/j.cmet.2019.08.015. Epub 2019 Aug 30.

Authors

David A Hess¹, Daniella C Terenzi², Justin Z Trac³, Adrian Quan⁴, Tamique Mason³, Mohammed Al-Omran⁵, Deepak L Bhatt⁶, Natasha Dhingra⁴, Ori D Rotstein⁷, Lawrence A Leiter⁸, Bernard Zinman⁹, Sandra Sabongui⁴, Andrew T Yan¹⁰, Hwee Teoh¹¹, C David Mazer¹², Kim A Connelly¹³, Subodh Verma¹⁴

Affiliations

¹ Division of Vascular Surgery, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Molecular Medicine Research Laboratories, Robarts Research Institute, London, ON, Canada; Department of Physiology and Pharmacology, Western University, London, ON, Canada. Electronic address: [email protected].
² Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
³ Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
⁴ Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
⁵ Division of Vascular Surgery, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Department of Surgery, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
⁶ Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, MA, USA.
⁷ Division of General Surgery, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada; Department of Surgery, University of Toronto, Toronto, ON, Canada.
⁸ Division of Endocrinology and Metabolism, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada.
⁹ Department of Medicine, University of Toronto, Toronto, ON, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
¹⁰ Division of Cardiology, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹¹ Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada; Division of Endocrinology and Metabolism, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
¹² Department of Anesthesia, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada; Department of Anesthesia, University of Toronto, Toronto, ON, Canada.
¹³ Division of Cardiology, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
¹⁴ Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Department of Surgery, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada. Electronic address: [email protected].

PMID: 31477497
DOI: 10.1016/j.cmet.2019.08.015

Abstract

Hess et al. quantified circulating aldehyde dehydrogenase-expressing (ALDH^hi) cell subsets in people with T2DM given either empagliflozin (EMPA) or placebo. EMPA treatment increased circulating pro-angiogenic CD133⁺ progenitor cells, decreased pro-inflammatory ALDH^hi granulocyte precursors, and increased ALDH^hi monocytes with M2 polarization. EMPA treatment improved T2DM-associated "regenerative cell depletion" contributing to enhanced vascular health.

Publication types

Letter
Randomized Controlled Trial

MeSH terms

Adult
Aged
Aged, 80 and over
Benzhydryl Compounds / pharmacology*
Benzhydryl Compounds / therapeutic use
Cardiotonic Agents / pharmacology*
Cardiotonic Agents / therapeutic use
Cardiovascular Diseases / complications
Cardiovascular Diseases / drug therapy*
Coronary Artery Disease / drug therapy*
Diabetes Mellitus, Type 2 / complications*
Glucosides / pharmacology*
Glucosides / therapeutic use
Humans
Middle Aged
Myeloid Progenitor Cells / drug effects*
Myeloid Progenitor Cells / physiology
Regeneration
Sodium-Glucose Transporter 2 Inhibitors / pharmacology*
Sodium-Glucose Transporter 2 Inhibitors / therapeutic use

Substances

Benzhydryl Compounds
Cardiotonic Agents
Glucosides
Sodium-Glucose Transporter 2 Inhibitors
empagliflozin