Effects of Exenatide on Coagulation and Platelet Aggregation in Patients with Type 2 Diabetes

Abstract

Objective: To explore the effect of the glucagon-like peptide-1 receptor agonist exenatide on coagulation function and platelet aggregation in patients with type 2 diabetes mellitus (T2DM).

Methods: Thirty patients with newly diagnosed T2DM were enrolled as the case group, and 30 healthy people with matching age and sex were selected as the control group. Patients in the case group received exenatide treatment for 8 weeks. The general clinical data and biochemical indicators of all subjects were collected; and their peripheral blood platelet count, coagulation index, nitric oxide (NO), platelet membrane glycoprotein (CD62p), platelet activation complex-1 (PAC-1) and platelet aggregation induced by collagen, epinephrine (EPI), arachidonic acid (AA), and adenosine diphosphate (ADP) were detected.

Results: The fibrinogen, CD62p, PAC-1, and platelet aggregation rates of the case group (pretreatment) are higher than those in the control group (EPI 77.90±6.31 vs 60.15±5.37, ADP 52.89±9.36 vs 47.90±6.16, and AA 76.09±3.14 vs.55.18±3.55); and the NO level is lower in the case group than in the control group (p<0.05, respectively). After 8 weeks of exenatide treatment in the case group, the CD62p, PAC-1, and platelet aggregation rates were lower than before the treatment (EPI: 61.96±8.94 vs 77.90±6.31 and AA: 50.98±6.73 vs 76.09±3.14); and the NO level was higher than before the treatment (p<0.05, respectively). Pearson correlation analysis showed that the changes in platelet aggregation rates (Δ EPI and ΔAA) of the patients in the case group after 8 weeks of exenatide treatment were positively correlated with the changes in body mass index, waist circumference, weight, blood lipids, fasting plasma glucose, haemoglobin A1c, fibrinogen, CD62p, and PAC-1 and negatively correlated with the changes in high-density lipoprotein and NO (p<0.05). Multiple linear regression analysis showed that the changes in NO, CD62p and PAC-1 were independent risk factors affecting the changes in platelet aggregation rates.

Conclusion: The GLP-1R agonist exenatide can inhibit the activation state of platelets in patients with T2DM and inhibit thrombosis, which is beneficial to reduce the risk of cardiovascular events.

Keywords: exenatide; glucagon-like peptide-1; platelet activation; thrombosis; type 2 diabetes mellitus.

Figure 1

(A) Pearson correlation analysis of platelet aggregation rates and other clinical parameters in the control group. Pearson correlation analysis showed that the platelet aggregation rates in the control group were positively correlated with BMI, weight, waist circumference, TCH, TG, LDL-C, FPG, HbA1c, CD62p and PAC-1 and negatively correlated with HDL-C and NO (p<0.05). (B) Pearson correlation analysis of platelet aggregation rates and other clinical parameters in the case group (pretreatment). Pearson correlation analysis showed that the platelet aggregation rates in the case group (pretreatment) were positively correlated with BMI, weight, waist circumference, TCH, TG, LDL-C, FPG, HbA1c, CD62p and PAC-1 and negatively correlated with HDL-C and NO (p<0.05).

Figure 2

Changes in CD62p and PAC-1 after 8 weeks of exenatide treatment were detected by three-colour flow cytometry. Three-colour flow cytometry was performed to detect platelet CD62p and PAC-1 (represented by the percentage of positive platelets for each activation marker) in whole-blood samples. The percentage represented more platelets positive for P-selectin/PAC-1.

Figure 3

Changes in platelet aggregation rates after 8 weeks of exenatide treatment were detected by light transmission aggregometry.

Figure 4

Pearson correlation analysis of the correlation between changes in the platelet aggregation rate (ΔEPI and ΔAA) and changes in other clinical parameters (r).