title: Alterations in gastrointestinal, endocrine, and metabolic processes after bariatric Roux-en-Y gastric bypass surgery.
abstract: OBJECTIVE
  Obesity leads to severe long-term complications and reduced life expectancy. Roux-en-Y gastric bypass (RYGB) surgery induces excessive and continuous weight loss in (morbid) obesity, although it causes several abnormal anatomical and physiological conditions.
  
  
  METHODS
  To distinctively unveil effects of RYGB surgery on β-cell function and glucose turnover in skeletal muscle, liver, and gut, nondiabetic, morbidly obese patients were studied before (pre-OP, five female/one male, BMI: 49 ± 3 kg/m(2), 43 ± 2 years of age) and 7 ± 1 months after (post-OP, BMI: 37 ± 3 kg/m(2)) RYGB surgery, compared with matching obese (CON(ob), five female/one male, BMI: 34 ± 1 kg/m(2), 48 ± 3 years of age) and lean controls (CON(lean), five female/one male, BMI: 22 ± 0 kg/m(2), 42 ± 2 years of age). Oral glucose tolerance tests (OGTTs), hyperinsulinemic-isoglycemic clamp tests, and mechanistic mathematical modeling allowed determination of whole-body insulin sensitivity (M/I), OGTT and clamp test β-cell function, and gastrointestinal glucose absorption.
  
  
  RESULTS
  Post-OP lost (P < 0.0001) 35 ± 3 kg body weight. M/I increased after RYGB, becoming comparable to CON(ob), but remaining markedly lower than CON(lean) (P < 0.05). M/I tightly correlated (τ = -0.611, P < 0.0001) with fat mass. During OGTT, post-OP showed ≥15% reduced plasma glucose from 120 to 180 min (≤4.5 mmol/L), and 29-fold elevated active glucagon-like peptide-1 (GLP-1) dynamic areas under the curve, which tightly correlated (r = 0.837, P < 0.001) with 84% increased β-cell secretion. Insulinogenic index (0-30 min) in post-OP was ≥29% greater (P < 0.04). At fasting, post-OP showed approximately halved insulin secretion (P < 0.05 vs. pre-OP). Insulin-stimulated insulin secretion in post-OP was 52% higher than before surgery, but 1-2 pmol/min(2) lower than in CON(ob)/CON(lean) (P < 0.05). Gastrointestinal glucose absorption was comparable in pre-OP and post-OP, but 9-26% lower from 40 to 90 min in post-OP than in CON(ob)/CON(lean) (P < 0.04).
  
  
  CONCLUSIONS
  RYGB surgery leads to decreased plasma glucose concentrations in the third OGTT hour and exaggerated β-cell function, for which increased GLP-1 release seems responsible, whereas gastrointestinal glucose absorption remains unchanged but lower than in matching controls.
authors.affiliation: Metabolic Unit, Institute of Biomedical Engineering, National Research Council, Padua, Italy. christian-heinz.anderwald@meduniwien.ac.at
authors.forename: Christian-Heinz
authors.initials: CH
authors.lastname: Anderwald
authors.forename: Andrea
authors.initials: A
authors.lastname: Tura
authors.forename: Miriam
authors.initials: M
authors.lastname: Promintzer-Schifferl
authors.forename: Gerhard
authors.initials: G
authors.lastname: Prager
authors.forename: Marietta
authors.initials: M
authors.lastname: Stadler
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ludvik
authors.forename: Harald
authors.initials: H
authors.lastname: Esterbauer
authors.forename: Martin Georg
authors.initials: MG
authors.lastname: Bischof
authors.forename: Anton
authors.initials: A
authors.lastname: Luger
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
authors.forename: Michael
authors.initials: M
authors.lastname: Krebs
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D015390:Gastric Bypass; D041981:Gastrointestinal Tract / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1