Gestational diabetes linked to increased platelet hyperreactivity

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There is a link between gestational diabetes mellitus (GDM) and platelet hyperreactivity lasting up to 2 months after delivery, according to a recent study published in the American Journal of Obstetrics & Gynecology.¹

Approximately 7% to 14% of pregnancies are impacted by GDM, which has been linked to long-term adverse health outcomes.² As increased thromboxane A2 (TxA2) and reduced prostacyclin (PGI2) are produced by the placenta during GDM, placental dysfunction has been considered by experts as a potential cause of perinatal complications.¹

According to investigators, “A greater understanding of the involvement of platelets in GDM and of its mechanisms can help to identify prognostic markers for the disorder and to define novel therapeutic targets to reduce… pregnancy complications.” Therefore, a study was conducted to evaluate platelet activation and hyperreactivity in women with GDM.

Participants included GDM cases on a dietary or insulin therapy and healthy pregnant women (HP) controls matched by gestational age. Glucose intolerance was required for inclusion in the GDM group. GDM diagnosis occurred by week 18 of gestation.

The first GDM evaluation occurred at weeks 26 to 28 of gestation, the second evaluation weeks 34 to 36 of gestation, and the third evaluation 8 weeks after delivery. During these evaluations, standard methods were used to assess blood glucose, hemoglobin A1c, cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol.

Platelet aggregation was measured based on adenosine diphosphate (ADP), collagen, arachidonic acid, and epinephrine (Epi) types, as well as U46619 (1 μM). Image software was used to assess platelet surface coverage.

Using flow cytometry, investigators measured P-selectin expression and αIIbβ3 receptor activation on platelets stimulated with thrombin receptor activating peptide-6 (TRAP-6) (4 μM) or ADP (10 μM). Assessments of reactive oxygen species (ROS) and nitric oxide (NO) production by platelets was also performed.

Indications of the International Society on Thrombosis and Hemostasis were used to evaluate activation antigen expression on the surface of circulating platelets. Platelet identification was based on forward scatter characteristics and positivity for CD41.

Additional measurements were performed for plasma soluble CD40L and soluble P-selectin levels. The EndoPAT System (Itamar Medical ltd, Caesarea, Israel) was used to measure in vivo endothelial function.

There were 46 women included in the final analysis, 23 of whom were in the HP group and 23 were in the GMD group. Similar total cholesterol, HDL and low-density lipoprotein–cholesterol, and triglycerides (TG) were reported between groups at enrollment.

Little change in these parameters were reported at 2 months after delivery except for a significant decline in TG for both groups. The GDM group presented with significantly increased fasting blood glucose levels at week 27 vs the HP group.

Women with GDM presented with significantly reduced half maximal effective concentration of collagen-induced aggregation compared to HP. GDM patients also had an increased maximal amplitude of platelet aggregation at week 27.

At week 35, increased reactivity was reported in both groups. However, levels remained significantly increased in GDM women with collagen, ADP, and arachidonic acid. Significant declines were reported in both groups 8 weeks after delivery.

Significantly reduced PFA-100 C/EPI closure time was also reported in GDM women vs HP women. However, significant differences in C/ADP closure time were not observed between groups

Women with GDM had significantly increased platelet adhesion to collagen and P-Sel during stimulation with ADP or TRAP. At all time points, significantly reduced platelet NO production was observed in GDM women vs HP women.

Investigators noted a negative correlation between NO production and low-dose collagen-induced platelet aggregation. ROS production was significantly higher in GDM women vs HP women at all 3 time points.

These results indicated a potential role of platelet hyperactivity toward long-term complications among women with GDM. Investigators concluded “it may represent a therapeutic target, for instance, for the use of low-dose aspirin or other antiplatelet agents to be explored.”

References

1. Guglielmini G, Falcinelli E, Piselli E, et al. Gestational diabetes mellitus is associated with in vivo platelet activation and platelet hyperreactivity. Am J Obstet Gynecol. 2025;232:120.e1-14. doi:10.1016/j.ajog.2024.04.003
2. Hyer SL, Shehata HA. Gestational diabetes mellitus. Curr Obstet Gynaecol. 2005;15(6):368-374. doi:10.1016/j.curobgyn.2005.09.011