In patients who develop hypoglycemic complications after gastric bypass surgery, postprandial insulin overresponse may be due to altered islet cell function and decreased insulin clearance, according to a study from the University of Cincinnati. A total of 65 patients who underwent gastric bypass more than 2 years before enrollment were included in this study and grouped according to history of postprandial hypoglycemia during the glucose tolerance test. Eleven patients with the same BMI but who had not undergone surgery were also included as a control group. The researchers conducted a cross-sectional analysis of the patients’ insulin secretion rate, pancreatic islets, and response responses to other glucagon hormones, such as gastrointestinal hormones, after consuming a liquid meal. All subjects maintained their usual carbohydrate intake during the day without any physical activity for 3 days, fasted overnight, and then ate 237 ml of a liquid mixed meal (35 kcal; 57% carbohydrate, 15% protein, 28% fat) the next day after baseline blood samples were collected, and then blood samples were collected again from 0 to 180 minutes later, and blood glucose levels were measured using an automated analyzer. The results of the study showed that patients who had undergone gastric bypass had a higher rate of glucose and insulin response, which occurred earlier after a liquid meal. Patients with a history of hypoglycemia had the strongest early insulin response and relatively lowest blood glucose level nadir, more so in patients with neurologic hypoglycemic symptoms (cognitive abnormalities, loss of consciousness, seizures) than in patients with vegetative nervous system symptoms (rapid heartbeat, sweating, tingling, fatigue). Patients who had undergone gastric bypass and experienced hypoglycemia were seen to have lower insulin clearance and higher insulin secretion rates during the drop in blood glucose after the meal test. Postprandial glucagon levels were elevated in all patients who underwent gastric bypass with or without hypoglycemia. In post-gastric bypass patients with or without symptoms of neurologic hypoglycemia, there were no differences in plasma gastrointestinal inhibitory peptide and glucagon-like peptide-1 levels between the two. The researchers concluded that in patients who have undergone gastric bypass and have a history of hypoglycemia, inappropriate insulin secretion and decreased insulin clearance often lead to hyperinsulinemia. In patients with symptoms of postprandial hypoglycemia, insulin secretion is also increased during the late postprandial glucose clearance period despite elevated glucagon levels and the absence of a distant response to hypoglycemia. These abnormalities in insulin function are most pronounced in patients with neurologic hypoglycemic symptoms.