An Analysis of Lipid and Glucose Metabolism Following Bariatric Surgery

Background: Bariatric surgery is the only evidence-based approach to efficacious and sustainable weight loss. It is estimated that about one third of patients undergoing bariatric surgery have type 2 diabetes, with a high rate of resolution of diabetes post-operatively: 84-98% after gastric bypass and 48-68% after purely restrictive procedures(1, 2). Other cardiovascular risk factors such as lipid profile and inflammatory markers also, significantly improve. 25% of the population of Alberta are obese and 2,7% are morbidly obese, one third of them are with type 2 diabetes. Bariatric surgery in these patients will translate into a cure for type II diabetes, dramatic improvements in quality of life, improved longevity and lower health care costs for the system.

Morbid obesity leads to elevated plasma free fatty acids (FFA) and subsequently to excessive accumulation of triglyceride in peripheral tissues. Excessive triglyceride accretion is an independent risk factor for insulin resistance, type II diabetes and cardiovascular complications. Bariatric surgery is associated with dramatic improvements in these comorbid diseases(2). Purely restrictive procedures (laparoscopic adjustable gastric band - LAGB) may differ from hybrid procedures (laparoscopic roux-en-y gastric bypass - LRYGB) in their effect on diabetes and cardiovascular disease. The LAGB is a less complex surgical procedure that can be done on a day surgery basis and has an extremely low peri-operative mortality rate. The LRYGB is much more complex and has a low but important rate of anastomotic leak and mortality.

LAGB and LRYGB vary in their average percent excess weight loss (%EWL)(2). This may contribute to a disparity in their impact on comorbid disease. However, improvements in insulin sensitivity and glucose homeostasis occur early after LRYGB, preceding significant weight loss(3). Postoperative changes in the absorption and metabolism of lipids induced by a malabsorptive procedure may be responsible for these beneficial changes. The relationship of improved insulin sensitivity to changes in lipid metabolism need to be clarified in order to understand the varying impact of LAGB and LRYGB on comorbid disease associated with obesity. The initial decreased caloric intake following Bariatric surgery can improve the response of adipose tissue manifested by favorable changes in adipocytokines. The postoperative rise in adiponectin (4, 7) (an anti-inflammatory mediator) was observed. These changes correlate with weight loss and improvement in insulin resistance.

In obese insulin-resistant subjects, insulin cannot attenuate hydrolysis of stored triglyceride in adipose tissue and consequently this leads to excessive free fatty acids release into circulation and increased delivery of fatty acids to the muscle, liver and pancreas. Excessive uptake of fatty acids into these tissues exacerbates hepatic and muscle insulin resistance and impairs insulin secretion from pancreatic beta cells. Bariatric surgery improves insulin sensitivity which leads to inhibition of hydrolysis of adipose triglycerides and decreased release of free FFA into the circulation. Recently it was shown that not only increased baseline FFA but also altered clearance of FFA normalize after LRYGB (8). Also, postoperative reduction in fat intake and absorption leads to decreased level of FFA in blood. After malabsorptive, weight-reducing procedures the beta cell glucose and fatty acid sensitivity was doubled early in diabetic patients, leading to a decrease in insulin secretion (9).

Beside its contribution to insulin resistance, severe obesity is also associated with an elevated inflammatory state. In obese with type 2 diabetes and metabolic syndrome, the highly sensitive C-reactive protein (CRP) serum concentration, an inflammatory marker, is increased and correlates with the severity of glucose intolerance and with the severity of inflammation (10). Following bariatric surgery, C-reactive protein (CRP) decreases. It has been shown that gastric bypass reduces biochemical cardiac risk factors, particularly, CRP by 80% in addition to triglycerides, total cholesterol, LDL, and lipoprotein A (7, 11).