Role of Adiponectine in Pathophysiology Ogf Diabetic Foot

Overview

Diabetic patients with a history of diabetic foot are considered to be a high-risk population for increased cardiovascular and all-cause mortality (1,2,3,). Diabetic foot (DF) is responsible for more hospitalizations than any other complication of diabetes and are the leading cause of non-traumatic lower extremity amputations, resulting in nearly 100 000 amputations annually in the US alone (4,5,6). Surgical debridement, as an important component of standard of care of diabetic foot, is intended to remove healing-impaired tissue, decreases bacterial burden, thus to stimulate overall wound closure, while removing as little of healing-competent skin as possible. Furthermore, debrided tissue is often used as a valuable tissue source for research purposes (7,8,9,10). Debrided tissue presents valuable diagnostic and research source to verify pathology, assess prognosis and gain insights into DF molecular pathology, all of which ultimately leads to improved outcomes. We aimed to validate tissue obtained from surgical debridement of DF for the cellular/molecular tissue analyses and biomarkers, to evaluate the pathophysiology of DF and understanding mechanisms that inhibit healing. The age range will be 50-70 years, in order to minimize the effects of irreversible vascular wall changes induced progressively by the aging process. All patients will undergo screening procedures that will include full anamnesis, physical examination, basic laboratory blood tests (full chemistry, CBC); urine examination and EKG will be performed at start and at the end of the study. Patients with a significant myocardial, and renal, cerebrovascular or hepatic disease will be excluded from the study. In a prospective study, we will collect wound edge tissue specimens from 75 patients with DF during surgical debridement. From each patient, 1-4 specimens will be obtained per debridement. To evaluate debrided tissue, each specimen will be processed for paraffin embedding and stained with haematoxylin and eosin. Histopathology analysis of multiple specimens acquired from the same wound will be analysed.

Diabetic patients with a history of diabetic foot are considered to be a high-risk population for increased cardiovascular and all-cause mortality (1,2,3,). Diabetic foot (DF) is responsible for more hospitalizations than any other complication of diabetes and are the leading cause of non-traumatic lower extremity amputations, resulting in nearly 100 000 amputations annually in the US alone (4,5,6). Surgical debridement, as an important component of standard of care of diabetic foot, is intended to remove healing-impaired tissue, decreases bacterial burden, thus to stimulate overall wound closure, while removing as little of healing-competent skin as possible. Furthermore, debrided tissue is often used as a valuable tissue source for research purposes (7,8,9,10). Debrided tissue presents valuable diagnostic and research source to verify pathology, assess prognosis and gain insights into DF molecular pathology, all of which ultimately leads to improved outcomes. We aimed to validate tissue obtained from surgical debridement of DF for the cellular/molecular tissue analyses and biomarkers, to evaluate the pathophysiology of DF and understanding mechanisms that inhibit healing. The age range will be 50-70 years, in order to minimize the effects of irreversible vascular wall changes induced progressively by the aging process. All patients will undergo screening procedures that will include full anamnesis, physical examination, basic laboratory blood tests (full chemistry, CBC); urine examination and EKG will be performed at start and at the end of the study. Patients with a significant myocardial, and renal, cerebrovascular or hepatic disease will be excluded from the study. In a prospective study, we will collect wound edge tissue specimens from 75 patients with DF during surgical debridement. From each patient, 1-4 specimens will be obtained per debridement. To evaluate debrided tissue, each specimen will be processed for paraffin embedding and stained with haematoxylin and eosin. Histopathology analysis of multiple specimens acquired from the same wound will be analysed. Full-thickness epidermis biopsies will be followed by biomarker assessment such as: 1. Expression of insulin-like growth factor 1 receptor (IGF-1R) 2. Adiponectin 3. Leptin 4. Resistin 5. Osteocalcin 6. Osteoprotegerin 7. Insulin, c-peptid 8. HOMA-IR Blood sampling for chemistry and metabolic markers including lipids, fasting glucose, fasting insulin, HbA1C, HOMA-IR , CRP, plasma adiponectin, visfatin, resistin, and plasma leptin will be performed. Additionally, relationship between serum and tissue adipokines level will be evaluated.