Investigation of the relationship between serum NLRP3 and NRF-2 levels and lower extremity arterial ischemia in patients with diabetic foot ulcers

In this thesis study, the relationship between the degree of lower extremity arterial ischemia and serum NLRP3 and NRF-2 levels in patients with diabetic foot ulcers, and the role of these biomarkers in the formation of diabetic foot ulcers were evaluated. Our study was conducted between November 1, 2023, and June 1, 2024, on 39 patients with diabetic foot ulcers, 42 diabetic patients without foot ulcers, and 41 healthy volunteers who presented to our hospital. The ankle-brachial index and peripheral arterial oxygen saturation of the toes were measured using a saturation probe to evaluate the lower extremity ischemia status in the cases. The arterial flow patterns and lower extremity arterial flow velocities of the patients were assessed using color Doppler ultrasonography of the anterior and posterior tibial arteries. The patients were also grouped according to the Wagner classification of diabetic foot ulcers. Serum NLRP3 and NRF-2 levels were measured from blood samples using the ELISA method. NLRP3 levels were significantly higher in the DM foot group (mean rank 86.87) compared to the type 2 DM group (mean rank 63.21) and the control group (mean rank 35.61) (p<0.001). NRF2 levels were significantly lower in the DM foot group (mean rank 34.58) compared to the type 2 DM group (mean rank 2.38) and the control group (mean rank 86.21) (p<0.001). In the DM foot group, patients with monophasic flow had significantly higher NLRP3 levels compared to those with biphasic and triphasic flow (p=0.016). In the DM foot group, female patients had higher NLRP3 levels compared to males (p=0.028). In male patients in the DM foot group with monophasic flow, NLRP3 levels were higher than in those with biphasic and triphasic flow (p=0.044). In the DM foot group, patients aged ≥40 years had higher NLRP3 levels compared to those under 40 years (p=0.010). In the DM foot group, patients aged ≥40 years with monophasic flow had higher NLRP3 levels compared to those with biphasic and triphasic flow (p=0.031). In conclusion, the finding of elevated serum NLRP3 levels and decreased NRF2 levels in patients with diabetic foot ulcers, along with their association with lower extremity arterial ischemia findings on Doppler ultrasonography, suggests the role of these molecules in the formation of diabetic foot ulcers. Therefore, interventions and treatments targeting these molecules in patients with diabetic foot ulcers may contribute to patient recovery. Keywords: Diabetic foot, flow pattern, peripheral artery disease, NLRP3, NRF2 Supporting Institution: GAÜN BAP Unit (Project Code: TF.UT.24.17)