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

Abstract

Abegg K, Corteville C, Docherty NG, Boza C, Lutz TA, Muñoz R, le Roux CW. 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. Am J Physiol Regul Integr Comp Physiol 308: R321-R329, 2015. First published December 24, 2014 doi:10.1152/ajpregu.00331.2014.-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 calorie restriction/weight loss and medical combination therapy-based approaches using the Zucker diabetic fatty rat (ZDF) rodent model of advanced T2DM. Male ZDF rats underwent RYGB (n ϭ 15) or SG surgery (n ϭ 10) at 18 wk 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, other groups of animals underwent sham surgery with ad libitum feeding (n ϭ 6), with body weight (n ϭ 8), or glycemic matching (n ϭ 8) to the RYGB group, using food restriction or a combination of insulin, metformin, and liraglutide, respectively. Both bariatric procedures decreased the daily insulin dose required to maintain mid-light-phase blood glucose levels below 15 mmol/l, compared with those required by body weight or glycemia-matched rats (P Ͻ 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 vs. RYGB at study end (P Ͻ 0.05). Severe hypoglycemia occurred in several rats after RYGB. RYGB and SG significantly improved glycemic control in a rodent model of advanced T2DM. While short-term outcomes are similar, long-term efficacy appears marginally better after RYGB, although this is tempered by the increased risk of hypoglycemia. bariatric surgery; Roux-en-Y gastric bypass; sleeve gastrectomy; glycemic control; medical therapy; caloric restriction; Zucker diabetic fatty rat ROUX-EN-Y GASTRIC BYPASS (RYGB) and vertical sleeve gastrectomy (SG) surgery can be used as a treatment alternative to intensive management in obese patients (body mass index Ͼ30 kg/m 2 ) with Type 2 diabetes mellitus (T2DM) (5, 29, 39).After these operations, most patients have improved glycemic control, and ϳ40% of patients achieve a HbA1c Ͻ42 mmol/ mol (6%) after one year. It remains controversial whether RYGB and SG lead to comparable rates of metabolic improvement and T2DM remission. Some studies report a higher T2DM remission rate or that glycemic targets can be achieved with fewer medications after RYGB compared with SG surgery (3, 22, 23, 32), while others show a similar glycemic outcome for both procedures (12,16,28,46). Data on longterm remission and relapse rates are scarce, but at 3 years, 38% of those after RYGB and 24% of those after SG had a HbA1c Ͻ42 mmol/l (6%) (39). The use ...

Roux‐en‐Y gastric bypass decreases endotoxemia and inflammatory stress in association with improvements in gut permeability in obese diabetic rats

“…22 The ZDF rat, a genetically engineered rat model of obesity associated with insulin resistance, dyslipidemia, and other complications, has been chosen to assess the effect of RYGB in many previous studies. [15][16][17][18][19]23 In the present study, RYGB surgery obviously decreased endotoxemia-associated indices, plasma LPS concentrations, and serum and adipose tissue concentrations of the inflammatory cytokines TNF-α and IL-1β. Recently, the inflammatory reaction in insulin resistance, obesity, and T2D has attracted increasing attention.…”

“…Therefore, research on the mechanism by which RYGB relieves diabetes‐associated obesity is important . The ZDF rat, a genetically engineered rat model of obesity associated with insulin resistance, dyslipidemia, and other complications, has been chosen to assess the effect of RYGB in many previous studies . In the present study, RYGB surgery obviously decreased endotoxemia‐associated indices, plasma LPS concentrations, and serum and adipose tissue concentrations of the inflammatory cytokines TNF‐α and IL‐1β.…”

“…Thus, we performed RYGB in Zucker diabetic fatty (ZDF) rats, a diabetic rat model of insulin resistance, dyslipidemia, and other complications. Many early and recent studies have used this experimental model to assess the effects of RYGB on glucose homeostasis . providing a quite precise approximation of obesity associated with T2D in humans.…”

“…Many early and recent studies have used this experimental model to assess the effects of RYGB on glucose homeostasis. [15][16][17][18][19] providing a quite precise approximation of obesity associated with T2D in humans. Based on a previous study 12 on the relationship between metabolism and gut microbiota following RYGB, in this study we further investigated the levels of inflammation and gut permeability after RYGB in ZDF rats and explored the relationship between inflammatory status and intestinal barrier integrity represented by specific tight junction proteins.…”

Roux-en-Y Gastric Bypass Improves Hepatic Glucose Metabolism Involving Down-Regulation of Protein Tyrosine Phosphatase 1B in Obese Rats

“…Among common bariatric procedures, Roux-en-Y gastric bypass (RYGB) surgery is considered the most effective procedure for producing long-term weight loss and metabolic improvement in obese patients. Glucose homeostasis has been reported to be improved prior to marked increases in weight loss and insulin sensitivity in both rodents and humans, particularly in the context of T2D [4,5], suggesting that the benefit effects of RYGB may not completely depend on food restriction and malabsorption. Previous studies have shown that RYGB promotes the secretion of incretins, such as glucagon-like peptide 1 (GLP-1), and improves the metabolic homeostasis [6,7,8,9].…”