Association of insulin therapy with clot strength in patients with diabetes with peripheral artery disease

Objective Patients with peripheral arterial disease (PAD) and diabetes mellitus are at an increased risk for thrombotic complications after revascularization. Whether insulin therapy is associated with altered coagulation profiles compared with oral antidiabetic therapy remains unclear. The aim of this study was to compare differences in coagulation profiles between patients with diabetes and PAD treated with insulin vs those treated with oral antidiabetic agents to evaluate the association of insulin therapy with viscoelastic coagulation parameters. Methods In this observational cohort, thromboelastography with platelet mapping was performed in patients with diabetes with PAD undergoing planned revascularization between December 2020 and March 2024 to document their objective coagulation states. Patients were stratified by diabetic treatment regimen (insulin vs 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, sex, body mass index, baseline hemoglobin A1c, presence of chronic kidney disease, and aspirin use. Results A total of 172 patients were analyzed, of whom 120 were treated with insulin. Baseline hemoglobin A1c was significantly higher in the insulin-treated group. Antiplatelet regimen distribution did not differ significantly between the groups. Insulin-treated patients demonstrated significantly higher unadjusted clot amplitude values, most notably arachidonic acid-mediated maximum amplitude (AA-MA) (45.5 mm [interquartile range, 25.7-60.0 mm] vs 27.4 mm [interquartile range, 17.4-49.0 mm]; P = .004 ). There were no significant differences in clot initiation (reaction time), fibrinolysis, citrated kaolin kinetics, or adenosine diphosphate-mediated platelet parameters. In adjusted analysis, insulin use remained independently associated with increased AA-MA (β = 8.36 mm (95% confidence interval [CI], 1.39-15.33; P = .019). Hemoglobin A1c was also independently associated with higher AA-MA (β = 2.04 mm per 1% increase; 95% CI, 0.05-4.03 mm per 1% increase; P = .045), whereas aspirin use was associated with lower AA-MA (β = −17.41 mm; 95% CI, −24.82 to −10.00 mm; P < .001). Conclusions Insulin therapy is independently associated with increased clot strength within the aspirin-sensitive AA-MA among patients with diabetes and PAD, 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 to achieve optimal therapeutic effect. Clinical Relevance Thrombotic complications after revascularization remain a major contributor to limb loss in patients with peripheral arterial disease, particularly among patients with diabetes. Our findings suggest that patients with diabetes receiving insulin therapy may represent a distinct subgroup characterized by persistent arachidonic acid-mediated platelet activation resulting in increased clot strength despite routine aspirin therapy. Recognition of this heterogeneity could guide further investigation into individualized strategies for thromboprophylaxis in these patients aimed at reducing thrombotic complications and improving limb preservation.