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:

• glucagon-like peptide-1
• type 2 diabetes mellitus
• exenatide
• platelet activation
• thrombosis

Acknowledgments

The authors thank the laboratory of Anhui Medical University and the participants of this study including statistician, doctors, nurses, and researchers from the First Affiliated Hospital of Anhui Medical University.

Abbreviations

ADP, adenosine diphosphate; AA, arachidonic acid; APTT, activated partial thromboplastin time; BMI, body mass index; COLL, collagen; cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate; DD, D-dimer; DBP, diastolic blood pressure; EPI, epinephrine; FPG, fasting plasma glucose; FIB, fibrinogen; FDP, fibrin degradation products; GLP-1R, glucagon-like peptide-1 receptor; HDL-C, high-density lipoprotein cholesterol; HbA1c, hemoglobin A1c; INR, international normalized ratio; LDL-C, low-density lipoprotein cholesterol; NO, nitric oxide; PLT, platelets; PT, prothrombin time; PTA, prothrombin time activity; PAC-1, platelet activation complex-1; PKG, protein kinase G; PI3K, phosphoinositide 3-kinase; PRP, platelet-rich plasma; PPP, platelet-poor plasma; RCT, randomized controlled trial; SBP, systolic blood pressure; sGC, soluble guanylate cyclase; TCH, total cholesterol; TG, triglycerides; TT, thrombin time; T2DM, type 2 diabetes mellitus; TGE, thromboelastogram.

Data Sharing Statement

The data sets used to support the findings of this study are available from the corresponding authors upon request.

Ethics Approval

According to the ethical principles of the “Measures for the Ethical Review of Biomedical Research Involving Humans”, the WMA “Declaration of Helsinki” and the CIOMS “International Ethical Guidelines for Human Biomedical Research”, the study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Anhui Medical University.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agreed to be accountable for all aspects of the work.

Disclosure

The authors declare no conflict of interest.

Additional information

Funding

This work was supported by the Natural Foundation of Anhui Province [NO.1808085MH279] and Discipline Construction Project of Anhui Medical University Project number [NO. 2021lcxk004].