title: 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: 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.
authors.affiliation: Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland;
authors.forename: Kathrin
authors.initials: K
authors.lastname: Abegg
authors.affiliation: Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland;
authors.forename: Caroline
authors.initials: C
authors.lastname: Corteville
authors.affiliation: Diabetes Complications Research Centre, Conway Institute, School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland;
authors.forename: Neil G
authors.initials: NG
authors.lastname: Docherty
authors.affiliation: Department of Digestive Surgery, School of Medicine Santiago, Pontificia Universidad Católica, Santiago, Chile;
authors.forename: Camilo
authors.initials: C
authors.lastname: Boza
authors.affiliation: Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland; Institute of Laboratory Animal Science, University of Zurich, Zurich, Switzerland; tomlutz@vetphys.uzh.ch.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Lutz
authors.affiliation: Department of Digestive Surgery, School of Medicine Santiago, Pontificia Universidad Católica, Santiago, Chile;
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Muñoz
authors.affiliation: Diabetes Complications Research Centre, Conway Institute, School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland; Gastrosurgical Laboratory, University of Gothenburg, Gothenburg, Sweden; and Investigative Science, Imperial College London, London, United Kingdom.
authors.forename: Carel W
authors.initials: CW
authors.lastname: le Roux
mesh_terms: D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D031204:Caloric Restriction; D003131:Combined Modality Therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004435:Eating; D005247:Feeding Behavior; D005743:Gastrectomy / Q000009:adverse effects; D015390:Gastric Bypass / Q000009:adverse effects; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000494:pharmacology; D007003:Hypoglycemia / Q000097:blood / Q000209:etiology; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000633:toxicity; D007328:Insulin / Q000494:pharmacology; D000069450:Liraglutide; D008297:Male; D008687:Metformin / Q000494:pharmacology; D009765:Obesity / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D011924:Rats, Zucker; D012307:Risk Factors; D013997:Time Factors; D015430:Weight Gain; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D008687:Metformin
keywords: Roux-en-Y gastric bypass; Zucker diabetic fatty rat; bariatric surgery; caloric restriction; glycemic control; medical therapy; sleeve gastrectomy