Gestational diabetes mellitus is associated with in vivo platelet activation and platelet hyperreactivity

Giuseppe Guglielmini; Emanuela Falcinelli; Elisa Piselli; Anna Maria Mezzasoma; Francesca Tondi; Luisa Alfonsi; Caterina De Luca; Valeria Fino; Alessandro Favilli; Sara Parrettini; Pietro Minuz; Elisabetta Torlone; Paolo Gresele; Sandro Gerli

doi:10.1016/j.ajog.2024.04.003

Gestational diabetes mellitus is associated with in vivo platelet activation and platelet hyperreactivity

Am J Obstet Gynecol. 2024 Apr 4:S0002-9378(24)00505-2. doi: 10.1016/j.ajog.2024.04.003. Online ahead of print.

Affiliations

¹ Division of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
² Division of Obstetrics and Gynecology, Centre of Perinatal and Reproductive Medicine, University of Perugia, Perugia, Italy.
³ Division of Endocrinology and Metabolism, S. Maria della Misericordia Hospital, Perugia, Italy; Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
⁴ Unit of General Medicine for the Study and Treatment of Hypertensive Disease, University of Verona, Verona, Italy.
⁵ Division of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy. Electronic address: paolo.gresele@unipg.it.

PMID: 38582292
DOI: 10.1016/j.ajog.2024.04.003

Abstract

Background: Gestational diabetes mellitus is associated with obstetrical and long-term cardiovascular complications. Although platelet hyperresponsiveness in type-2 diabetes mellitus has been well characterized and has been shown to play a crucial role in cardiovascular complications, this aspect has been little studied in gestational diabetes mellitus.

Objective: We aimed to evaluate platelet reactivity, in vivo platelet activation, and endothelial function in gestational diabetes mellitus in comparison with normal pregnancy.

Study design: This was a prospective, case-control study of 23 women with gestational diabetes mellitus and 23 healthy pregnant women who were studied at 26 to 28 and 34 to 36 weeks of gestation and at 8 weeks postpartum. Platelet reactivity and in vivo platelet activation, including light transmission aggregometry, PFA-100, platelet activation antigen expression, platelet adhesion under flow, platelet nitric oxide and reactive oxygen species production, and endothelial dysfunction markers, were assessed.

Results: The study of platelet function showed a condition of platelet hyperreactivity in cases with gestational diabetes mellitus when compared with healthy pregnant women at enrollment, which was further enhanced at the end of pregnancy and tended to decrease 2 months after delivery, although it still remained higher in gestational diabetes mellitus. In vivo platelet activation was also evident in gestational diabetes mellitus, especially at the end of pregnancy, in part persisting up to 8 weeks after delivery. Finally, women with gestational diabetes mellitus showed defective platelet nitric oxide production and endothelial dysfunction when compared with healthy pregnancies.

Conclusion: Our data showed that gestational diabetes mellitus generates a condition of platelet hyperreactivity that in part persists up to 2 months after delivery. Impaired platelet sensitivity to nitric oxide and reduced platelet and endothelial nitric oxide production may contribute to the platelet hyperreactivity condition. Platelet hyperreactivity may play a role in the long-term cardiovascular complications of gestational diabetes mellitus women.

Keywords: GDM pregnancy; endothelial dysfunction; gestational diabetes mellitus; in vitro platelet reactivity; in vivo platelet activation; nitric oxide; platelet hyperreactivity; platelets; reactive oxygen species.