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. 2015 Feb 15;308(4):R321-9. doi: 10.1152/ajpregu.00331.2014. Epub 2014 Dec 24.

Abstract

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 = 15) or SG surgery (n = 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 = 6), with body weight (n = 8), or glycemic matching (n = 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 < 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 < 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.

Keywords: Roux-en-Y gastric bypass; Zucker diabetic fatty rat; bariatric surgery; caloric restriction; glycemic control; medical therapy; sleeve gastrectomy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Behavior, Animal
  • Biomarkers / blood
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Caloric Restriction*
  • Combined Modality Therapy
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Eating
  • Feeding Behavior
  • Gastrectomy* / adverse effects
  • Gastric Bypass* / adverse effects
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptide 1 / pharmacology
  • Hypoglycemia / blood
  • Hypoglycemia / etiology
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / toxicity
  • Insulin / pharmacology
  • Liraglutide
  • Male
  • Metformin / pharmacology
  • Obesity / blood
  • Obesity / physiopathology
  • Obesity / therapy*
  • Rats, Zucker
  • Risk Factors
  • Time Factors
  • Weight Gain
  • Weight Loss / drug effects*

Substances

  • Biomarkers
  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Metformin