Effect of bariatric surgery combined with medical therapy versus intensive medical therapy or calorie restriction and weight loss on glycemic control in Zucker diabetic fatty rats

Background: Bariatric surgery rapidly improves type 2 diabetes mellitus (T2DM). Our objective was to profile and compare the extent and duration of improved glycemic control following Roux-en-Y gastric (RYGB) bypass surgery and vertical sleeve gastrectomy (SG) and compare against caloric restriction/weight loss and medical combination therapy based approaches using the Zucker diabetic fatty rat (ZDF) rodent model of advanced T2DM. Methods: Male ZDF rats underwent RYGB (n=15) or SG surgery (n=10) at 18 weeks of age and received postsurgical insulin treatment as required to maintain mid light phase glycemia within a predefined range (10-15 mmol/L). In parallel, further groups of animals underwent sham surgery with ad libitum feeding (n=6), with bodyweight (n=8) or glycemic matching (n=8) to the RYGB group using food restriction or a combination of insulin, metformin and liraglutide respectively. Results: Both bariatric procedures decreased the daily insulin dose required to maintain mid light phase blood glucose levels below 15 mmol/L as compared to those required by bodyweight or glycemic matched rats (p < 0.001). No difference was noted between RYGB and SG with regard to initial efficacy. SG was however associated with higher food intake, weight regain and higher insulin requirements versus RYGB at study end (p < 0.05). Severe hypoglycemia occurred in several rats after RYGB. Conclusions: RYGB and SG significantly improved glycemic control in a rodent model of advanced T2DM. Whilst short-term outcomes are similar, long-term efficacy appears marginally better after RYGB although this is tempered by the increased risk of hypoglycemia.