Alterations in Gastrointestinal, Endocrine, and Metabolic Processes After Bariatric Roux-en-Y Gastric Bypass Surgery

Abstract

OBJECTIVEObesity 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.RESEARCH DESIGN AND METHODSTo 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/m2, 43 ± 2 years of age) and 7 ± 1 months after (post-OP, BMI: 37 ± 3 kg/m2) RYGB surgery, compared with matching obese (CONob, five female/one male, BMI: 34 ± 1 kg/m2, 48 ± 3 years of age) and lean controls (CONlean, five female/one male, BMI: 22 ± 0 kg/m2, 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.RESULTSPost-OP lost (P < 0.0001) 35 ± 3 kg body weight. M/I increased after RYGB, becoming comparable to CONob, but remaining markedly lower than CONlean (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/min2 lower than in CONob/CONlean (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 CONob/CONlean (P < 0.04).CONCLUSIONSRYGB 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.