Abstract:Salam Hama (The University of Manchester) Degree Title: Doctor of Philosophy in the Faculty of Medical and Human SciencesThesis Title: Investigating Changes in the Composition and the Function of High Density Lipoprotein after Roux-n-Y Roux-n-Y Bariatric Surgery (2013).Background: Obesity is a major modifiable risk factor for cardiovascular disease (CVD). High Density Lipoprotein (HDL) functionality alters during obesity. Roux-n-Y Bariatric Surgery offers the best results for weight reduction, especially in obese patients with diabetes mellitus.Aim: the aim of this study is to investigate improvements in lipid metabolism after Roux-n-Y Bariatric Surgery, especially changes in HDL function and composition. Methods: 28 healthy volunteers and 27 obese patients, 11 with type 2 diabetes, were recruited. Lipid, glycaemic and vascular biomarkers were measured by ELISA and 3rd Generation Auto-analyser techniques. In vitro Oxidation was assessed by measurement of Lipid Peroxide (LPO) in mixtures of Low Density Lipoprotein (LDL) and HDL. Results: One year after surgery triglycerides and HDL-Cholesterol were significantly changed. Total cholesterol only reduced significantly in obese non-diabetic patients. Serum Paraoxonase1 (PON1) activity decreased six months after surgery, but increased significantly over the following six months. Despite this, PON1 activity remained significantly lower than pre-operative levels in the obese diabetic patients. LPO concentration in LDL had increased six months after surgery, but decreased significantly by one year. LPO in HDL also decreased one year after surgery but the reduction was only significant in obese non-diabetic patients. Fasting blood glucose, HbA1c and insulin decreased significantly in all obese patients. TNFalpha, IL-6, hsCRP, resistin, MCP-1, ICAM-1, VCAM-1, E-selectin, leptin and ASP decreased significantly one year after surgery. Small-dense LDL decreased while oxidised LDL (oxLDL) increased after surgery, but not significantly in the obese non-diabetic patients. Conclusions: Lipid and glucose metabolism and vascular inflammatory biomarkers improved after surgery. These changes are likely to contribute to morbidity and mortality improvement in morbidly obese patients after surgery. My results suggest that non-diabetic patients may draw a greater benefit from Roux-n-Y Bariatric Surgery than those with Type 2 Diabetes Mellitus suggesting a role for early gastric bypass surgery before complications of obesity develop. LDL oxidizability is greater in the first six months but the high concentration of in vivo oxLDL one year after surgery warrants further investigation.
|Date of Award||1 Aug 2014|
- The University of Manchester
|Supervisor||Paul Durrington (Supervisor), Deepak Bhatnagar (Supervisor) & Handrean Soran (Supervisor)|