title: Improved glucose metabolism after gastric bypass: evolution of the paradigm.
abstract: BACKGROUND
  Glucose metabolism is improved in patients with type 2 diabetes after Roux-en-Y gastric bypass (RYGB).
  
  
  OBJECTIVE
  To quantify the relative contribution of calorie restriction, rerouting of nutrients, and adipose tissue reduction.
  
  
  METHODS
  University Hospital.
  
  
  METHODS
  Fifteen diabetic patients, (47±9 yr, body mass index 41.3±4.2 kg/m2) were randomized to a 2-week very low-calorie diet (VLCD) regimen or normal diet before RYGB. A euglycemic-hyperinsulinemic clamp, indirect calorimetry, and a standard meal test were performed prediet, postdiet (preoperatively), and 2 weeks and 12 months postoperatively. The primary outcome was whole-body insulin sensitivity (M) measured with the clamp 2 weeks postoperatively.
  
  
  RESULTS
  In the VLCD group, after 2 weeks of calorie restriction, M improved (2.9±1.3 to 4.2±1.1 mg/kg/min, P = .005) with no further change at 2 weeks postoperatively. In the normal diet group 2 weeks postoperatively, M was similar to the VLCD group (4.7±1.7 versus 4.2±1.1, P = .61). One year postoperatively, M improved further in both groups. The improvement in insulin-stimulated glucose uptake after VLCD and RYGB was entirely accounted for by nonoxidative glucose disposal (NOGD), whereas weight loss at 1 year postoperatively was associated with an increase in NOGD and glucose oxidation. Postprandial glucose improved after VLCD (P<.05) and even more 2 weeks after RYGB (P<.05) with no further change after 1 year.
  
  
  CONCLUSIONS
  Improved whole-body insulin sensitivity and postprandial glucose response occur early after RYGB. Low calorie intake and rerouting of nutrients contribute through distinct mechanisms. Weight loss contributes by increasing whole-body insulin sensitivity, including glucose oxidation and NOGD. These data suggest that the combination of different mechanisms is what makes RYGB an effective intervention for type 2 diabetes.
authors.affiliation: The Norfolk and Norwich Oesophagogastric Cancer Centre, Norfolk and Norwich University Hospital, Colney Lane, Norwich, UK. Electronic address: dpournaras@doctors.org.uk.
authors.forename: Dimitri J
authors.initials: DJ
authors.lastname: Pournaras
authors.affiliation: Department of Surgery, Ersta Hospital, Stockholm, Sweden; Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Nygren
authors.affiliation: Department of Medicine, H7, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Hagström-Toft
authors.affiliation: Department of Medicine, H7, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
authors.affiliation: Diabetes Complication Research Centre, UCD Conway Institute, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland; Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden; Investigative Science, Imperial College London, London, UK.
authors.forename: Carel W
authors.initials: CW
authors.lastname: le Roux
authors.affiliation: Department of Surgery, Ersta Hospital, Stockholm, Sweden; Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Thorell
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism*; D031204:Caloric Restriction; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000178:diet therapy / Q000601:surgery*; D005260:Female; D015390:Gastric Bypass; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000097:blood / Q000178:diet therapy / Q000601:surgery; D019518:Postprandial Period; D011300:Preoperative Care / Q000379:methods
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose
keywords: Bariatric surgery; Diabetes mellitus type 2; Gastric bypass; Glucose clamp technique; Insulin resistance; Obesity; Randomized controlled trial