Effect of Ghrelin on Glucose Tolerance after Sleeve Gastrectomy

Introduction: Ghrelin is an appetite-stimulating peptide hormone secreted from the gastric mucosa in the fasting state that decreases in response to food intake. After sleeve gastrectomy (SG) , plasma levels of ghrelin decrease dramatically, whether this may influence glucose tolerance is unknown. We therefore investigated the effects of physiological ghrelin infusions on glucose tolerance in individuals with obesity before and after SG. Methods: Nine morbidly obese individuals with normal glucose tolerance, scheduled for SG, were enrolled. Four-hour standard mixed-meal tests with concomitant patient-blinded infusions of either acyl-ghrelin (1 pmol/kg/min) or placebo (saline) were performed in randomized order before and 3 months after surgery. All values are mean ± SEM. Results: Before SG, fasting plasma glucose was unaffected by ghrelin infusion, whereas both peak (7.93 ± 0.3 mmol/L versus 6.98 ± 0.2, p<0.001) and total area under the curve (tAUC) of plasma glucose concentrations (1874 ± 61 mmol/L*min versus 1702 ± 42, p=0.03) increased significantly during ghrelin infusion versus placebo. After SG, fasting plasma glucose was again unaffected by ghrelin infusion, whereas peak of plasma glucose increased (8.65 ± 0.5 mmol/L versus 7.92 ± 0.3 mmol/L, p=0.04) and tAUC of plasma glucose tended to increase (1817 ± 73 mmol/L*min versus 1636 ± 44 mmol/l*min, p=0.054) during ghrelin infusions versus placebo. The increase in tAUC during ghrelin infusion versus placebo was 10% before surgery and 11% after SG (p=0.98) . Conclusion: Ghrelin infusions increased postprandial plasma glucose concentrations in obese individuals both before and following SG, suggesting a role of ghrelin in the regulation of postprandial glucose metabolism. This response appears to be maintained following SG and the low levels of ghrelin after SG may thus contribute to the improved glucose control after the operation. Disclosure N.Hedbäck: None. S.Madsbad: None. M.Dichman: None. C.Dirksen: None. K.N.Bojsen-moller: None. N.B.Jørgensen: Advisory Panel; Novo Nordisk A/S, Research Support; Boehringer Ingelheim International GmbH, Speaker's Bureau; Novo Nordisk A/S, Stock/Shareholder; Eli Lilly and Company, Novo Nordisk A/S. M.G.Hindsø: Research Support; Novo Nordisk Foundation. V.B.Kristiansen: None. J.J.Holst: Advisory Panel; Novo Nordisk, Board Member; Antag Therapeutics, Bainan Biotech. M.S.Svane: None. Funding European Research Council (Grant 695069-BYPASSWITHOUTSURGERY) Novo Nordisk Foundation