Investigation of the Relationship between Gremlin-1 Levels and Wagner Classification in Diabetic Foot Patients and Evaluation of Its Usability as a Biomarker in the Progress to Amputation
Project no. 21555 · Status: Kapanmış (Yayın bekleniyor) · 2020
Summary
Objective: Diabetic foot (DF), one of the microvascular complications of diabetes, usually occurs as a result of neuropathy and ischemia. DF causes severe complications including tissue and organ loss, prolonged hospital stay, and psychosocial trauma with high morbidity and mortality. 60% of non-traumatic foot amputations are performed due to diabetic foot. The main elements of the DFS therapy are to accurate evaluation of DF, knowing the prognosis of the diasease and taking precautions. Gremlin-1 is a member of the TGF-ß superfamily that can act as a BMP antagonist and also it has been identified as a ligand of VEGFR2. It plays a key role in the development of muscles, skeletons and organs in embryogenesis, diseases which are accompaniying with fibrosis of various organs in adult life, and a number of mechanisms such as osteogenesis, angiogenesis, and hematopoiesis. In our study, we aimed to evaluate the relationship between serum Gremlin-1 levels and severity of the disease through Wagner staging in diabetic foot patients and to assess the prognostic value of Gremlin-1 levels for predicting amputation. Method: Eighty-five patients who applied to Ege University Faculty of Medicine Endocrinology Department either with foot wounds due to diabetes or high risk to develop DF were included in the study. The patients' age, gender, height, weight, diabetes type, diabetes duration, presence of diabetes complications and smoking habits were received, laboratory test results were obtained from the outpatient clinic files. Wagner classification of the patients was made and their ABIs were measured. Blood was drawn from the patients and the Gremlin-1 level was analyzed by ELISA method. Results: It was found that while the Wagner level of the DF increased, Gremlin-1 values liminally decreased statistically significant (p=0.05). In the patient group who underwent amputation, Gremlin-1 level decreased significantly (p <0.05). To predict the amputation, the sensitivity of Gremlin-1 level was 67% and specificity 46% at the cut-off value of 2,47 ng/ml. Furthermore, positive correlations were found between total cholesterol, LDL, fasting glucose and gremlin-1 levels(p <0.05). Gremlin-1was significantly increased significantly in the patient group who have HbA1c value> 7,5% (p <0.05). Serum Gremlin-1 levels were significantly decreased in patients with albuminuria (p <0.05). Conclusion: In diabetic foot patients, it was found that Gremlin-1 functioned by an unknown mechanism and while the Wagner level increased, the Gremlin-1 level was decreased. Therefore, it was determined that statistically meaningful especially in events with amputation. vi It has been shown that Gremlin-1 can be a prognostic marker to predict amputation. Comprehensive studies are required to elucidate the role and pathophysiology of Gremlin-1 in diabetic foot patients.