RS19 - The Impact of Insulin Therapy on Clot Strength in Diabetic Patients with Peripheral Artery Disease

Objectives: Patients with peripheral arterial disease (PAD) and diabetes are at an increased risk for thrombotic complications following revascularization. This is because diabetes creates a pro-thrombotic state through platelet hyperreactivity, excess coagulation signaling, and impaired fibrinolysis. However, there is a paucity of data regarding the impact of diabetic therapies (oral medication versus insulin) on an individual’s coagulative state. The aim of this study was to compare differences in coagulation profiles between diabetic PAD patients treated with insulin versus oral anti diabetic agents to determine the impact of diabetic treatment choice on coagulative states.

Methods: In this observational cohort, thromboelastography with platelet mapping (TEG-PM) was performed in diabetic patients with PAD undergoing planned revascularization between December 2020 and March 2024 to document their objective coagulation states. Patients were stratified by diabetic treatment regime (insulin versus oral medications). Global coagulation parameters, fibrin-mediated clot strength, and pathway-specific platelet function were assessed. Mann–Whitney U testing was used to compare groups. Multivariable linear regression was performed in patients to evaluate the independent association of insulin use with clot amplitude measures adjusting for age, BMI, baseline hemoglobin A1c and antiplatelet use.

Results: A total of 172 patients were analyzed, of whom 120 were treated with insulin. Baseline HbA1c was significantly higher in the insulin treated group. Antiplatelet regimen distribution did not differ significantly between groups. Insulin-treated patients demonstrated significantly higher unadjusted clot amplitude values, most notably arachidonic acid–mediated maximum amplitude (AA-MA) (43.3 vs 33.2 mm; p< 0.05) indicating that patients on insulin were pro-thrombotic (Figure 1). There were no significant differences in clot initiation (R time), fibrinolysis (LY30), citrated kaolin kinetics, or Adenosine diphosphate-mediated platelet parameters. In the multivariable regression model (Table I) adjusting for age, BMI, HbA1c, and aspirin use, insulin use remained independently associated with increased AA-MA (p < 0.05). HbA1c was also independently associated with higher AA-MA (p < 0.05), while aspirin use was associated with lower AA-MA (p < 0.001).

Conclusions: Insulin therapy is independently associated with increased clot strength within the aspirin-sensitive arachidonic acid pathway (AA-MA) among diabetic PAD patients even after accounting for differences in glycemic control. These findings suggest that insulin-treated patients may have persistent AA-mediated platelet activity despite routine aspirin therapy, supporting further study of individualized antiplatelet strategies as these patients may require increased platelet medications or doses to achieve a therapeutic effect.