Gut hormone secretion in a new meal tolerance test on insulin, glucagon, and glycemic excursions in patients with morbid obesity undergone sleeve gastrectomy

We have reported that hypoglycemia during a 75-g oral glucose tolerance test (OGTT) in patients who underwent a laparoscopic sleeve gastrectomy (LSG) is prevented by a new mixed meal tolerance test (MTT) containing lipid, protein, and carbohydrate equivalent to 75-g glucose. We investigated whether the secretions of gut hormones, including glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glicentin during OGTT, were involved in reactive hypoglycemia observed in post-LSG patients through changes in plasma insulin and glucagon secretions. Thus, we compared these gut hormone secretions during the OGTT and MTT in 30 Japanese patients pre- and 1-yr post-LSG. Both GLP-1 and glicentin secretions were glucose-dependently stimulated in pre-LSG patients and were enhanced by the LSG. This enhancement was associated with postprandial hypoglycemia through both enhanced acute insulin secretion and suppressed glucagon secretion during the OGTT in the post-LSG patients whose calculated disposition index improved. Conversely, the MTT in the post-LSG patients attenuated the insulin secretion and enhanced both GIP and glucagon secretions, resulting in protection of hypoglycemia. The GIP secretion was stimulated during the OGTT without association with insulin secretion, and the baseline GIP levels were positively correlated with HOMA-R in both pre- and post-LSG patients. In conclusion, the glucose-induced glicentin and GLP-1 secretions were associated with glucose-induced postprandial hypoglycemia through an overstimulation of acute insulin secretion in post-LSG patients. The new MTT is useful to evaluate normalization of glucose tolerance through attenuation of glucose-stimulated glicentin and GLP-1 secretions and enhanced GIP and glucagon secretions in post-LSG patients.<b>NEW & NOTEWORTHY</b> In postlaparoscopic sleeve gastrectomy (LSG) patients with enhanced disposition index, the standard OGTT resulted in postprandial reactive hypoglycemia, precluding accurate assessment of glucose tolerance. Glucose-induced glicentin and GLP-1 secretions were implicated in this phenomenon. However, a mixed meal test using 75-g carbohydrate, fat, and protein attenuated such reactive hypoglycemia, providing an accurate assessment of glucose tolerance through attenuation of both glicentin and GLP-1 oversecretions and enhanced GIP and glucagon secretions in post-LSG patients.