Abstract 11756: Tracking High-Density Lipoprotein Functionality in Diabetic and Non-Diabetic Patients With Toe Amputations

Abstract

Introduction: High-density lipoprotein cholesterol (HDL-c) levels have an established inverse association with cardiovascular event risk. More recently, the focus has shifted to HDL functionality as an improved metric of its predictive value and is impaired in patients with coronary arterial disease. HDL-c levels have been reported to inversely associate with the risk of amputation in patients with diabetic foot ulcers (DFUs), but whether HDL functionality is predictive of wound closure success is currently unknown. Methods: Eighteen diabetic and eight non-diabetic patients with toe/s amputations had blood collected at: (1) the time of surgery, (2) four weeks and (3) six months post-amputation. Wound areas were tracked until closure by 3D camera. Blood was collected from 20 healthy age and gender-matched participants. From blood, HDL was isolated and its functionality tested via (1) cholesterol efflux from macrophages, and (2) anti-inflammatory and (3) pro-angiogenic effects in endothelial cells. Results: Wound closure was faster in non-diabetic than diabetic amputation patients at four weeks (186.6%, P =0.12). Diabetic HDL promoted less cholesterol efflux at four-weeks (37.8%, P <0.05) and six-months (45.6%, P <0.01) post-amputation, compared to non-diabetic HDL. Incubation of non-diabetic HDL with endothelial cells caused greater reductions in inflammatory markers RELA (51.4%, P <0.01), CCL5 (46.9%, P <0.01), CCL2 (15.3%, P <0.05) and ICAM-1 (33.1%, P <0.05) than non-diabetic HDL. Non-diabetic HDL elicited greater endothelial cell angiogenesis with increased Matrigel tubule number at four weeks post amputation (46.15%, P <0.05), compared to diabetic HDL. There were significant correlations between the rate of wound closure and HDL-c levels (R 2 = +0.62, P <0.05), CCL2 (R = -0.64, P <0.05) and ICAM-1 (R = -0.71, P <0.05). Conclusion: In toe amputation patients, HDL-c levels and inflammatory HDL functionality markers associate with the rate of wound closure. HDL from diabetic patients had impaired cholesterol efflux capacity, reduced anti-inflammatory effects and was less able to promote angiogenesis, compared to non-diabetic HDL.