Journal
DIABETES CARE
Volume 35, Issue 12, Pages 2580-2587Publisher
AMER DIABETES ASSOC
DOI: 10.2337/dc12-0197
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Funding
- Austrian Society of Internal Medicine
- WWTF (Vienna Science and Technology Fund)
- European Union [QLG1-CT-2001-01252]
- AstraZeneca
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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. RESEARCH DESIGN AND METHODS-To distinctively unveil effects of RYGB surgery on beta-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 (CONob, five female/one male, BMI: 34 +/- 1 kg/m(2), 48 +/- 3 years of age) and lean controls (CONlean, 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 b-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 CONob, but remaining markedly lower than CONlean (P < 0.05). M/I tightly correlated (tau = 20.611, 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 beta-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 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). CONCLUSIONS-RYGB surgery leads to decreased plasma glucose concentrations in the third OGTT hour and exaggerated beta-cell function, for which increased GLP-1 release seems responsible, whereas gastrointestinal glucose absorption remains unchanged but lower than in matching controls.
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