title: Effects of gastric bypass surgery on insulin resistance and insulin secretion in nondiabetic obese patients.
abstract: Roux-en-Y-Gastric-Bypass (RYGB) reduces overall and diabetes-specific mortality by 40% and over 90%. This study aims to gain insight into the underlying mechanisms of this effect. We evaluated time-courses of glucose, insulin, C-peptide, and the incretin glucagon like peptide-1 (GLP-1) following an oral glucose load. Insulin-sensitivity was measured by a hyperinsulinemic-isoglycemic-clamp-test; glucose-turnover was determined using D-[6,6-(2)H(2)] glucose. Examinations were performed in six nondiabetic patients with excess weight before (PRE: BMI: 49.3 ± 3.2 kg/m(2)) and 7 months after RYGB (POST: BMI: 36.7 ± 2.9 kg/m(2)), in a lean (CON: BMI: 22.6 ± 0.6 kg/m(2)) and an obese control group (CONob) without history of gastrointestinal surgery (BMI: 34.7 ± 1.2 kg/m(2)). RYGB reduced fasting plasma concentrations of insulin and C-peptide (P < 0.01, respectively) whereas fasting glucose concentrations remained unchanged. After RYGB increase of C-peptide concentration following glucose ingestion was significantly higher compared to all other groups (dynamic-area under the curve (Dyn-AUC): 0-90 min: POST: 984 ± 115 ng·min/ml, PRE: 590 ± 67 ng·min/ml, CONob: 440 ± 44 ng·min/ml, CON: 279 ± 22 ng·min/ml, P < 0.01 respectively). Early postprandial increase of glucose concentration was however not affected. GLP-1 concentrations following glucose ingestion were sixfold higher after RYBG than before (P = 0.01). Insulin-stimulated glucose uptake tended to increase postoperatively (M-value: PRE: 1.8 ± 0.5, POST: 3.0 ± 0.3, not significant (n.s.)). Endogenous glucose production (EGP) was unaffected by RYGB. Hepatic insulin resistance index improved after RYGB and was then comparable to both control groups (PRE: 29.2 ± 4.3, POST: 12.6 ± 1.1, P < 0.01). RYGB results in hyper-secretion of insulin and C-peptide, whereas improvements of insulin resistance are minor and seem to occur rather in the liver and the adipose tissue than in the skeletal muscle.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Miriam
authors.initials: M
authors.lastname: Promintzer-Schifferl
authors.forename: Gerhard
authors.initials: G
authors.lastname: Prager
authors.forename: Christian
authors.initials: C
authors.lastname: Anderwald
authors.forename: Martina
authors.initials: M
authors.lastname: Mandl
authors.forename: Harald
authors.initials: H
authors.lastname: Esterbauer
authors.forename: Soheila
authors.initials: S
authors.lastname: Shakeri-Leidenmühler
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
authors.forename: Marietta
authors.initials: M
authors.lastname: Stadler
authors.forename: Martin G
authors.initials: MG
authors.lastname: Bischof
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ludvik
authors.forename: Aanton
authors.initials: A
authors.lastname: Luger
authors.forename: Michael
authors.initials: M
authors.lastname: Krebs
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism; D005260:Female; D015390:Gastric Bypass; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology; D007328:Insulin / Q000097:blood* / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008099:Liver / Q000378:metabolism; D008297:Male; D009767:Obesity, Morbid / Q000097:blood* / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D019518:Postprandial Period
chemical_list: D001786:Blood Glucose; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D002097:C-Reactive Protein