Relationship between biochemical and symptomatic hypoglycemia after RYGB. Responses to a mixed meal test: a case-control study

Background: Postprandial hypoglycemia is a relatively common complication after Roux-en-Y gastric bypass (RYGB). The cause remains incompletely understood, and the association between biochemical hypoglycemia and hypoglycemic symptoms is unclear. Objectives: To evaluate the association between postprandial hormonal responses and biochemical and symptomatic hypoglycemia after RYGB. Setting: University Hospital, Denmark. Methods: A case-control study with 3 groups: (1) RYGB group with postprandial hypoglycemic symptoms (HS), n = 13; (2) RYGB-group with no symptoms of hypoglycemia (NHS), n = 13; and (3) nonoperated body mass index-matched controls (CON), n = 7. Plasma glucose (PG) and hormonal responses (insulin, glucagon-like peptide-1, gastric inhibitory polypeptide, glucagon) were measured after a mixed meal test (MMT), and hypoglycemic symptoms were determined by a questionnaire. The primary outcomes were differences in subjective and biochemical responses related to hypoglycemia among the 3 groups. Results: Nadir PG was lower (3.1 versus 4.0 mmol/L (56 versus 72 mg/dL); P = .0002) and peak insulin higher in HS than NHS patients (1073 versus 734 pmol/L; P = .0499). Of the 13 patients with a peak insulin >850 pmol/L, 8 patients developed symptoms whereas only 2 out of the 13 patients with peak insulin <= 850 pmol/L developed symptoms, corresponding to an odds ratio of 12 (1.8; 81.7). Post hoc analyses comparing all RYGB patients with biochemical hypoglycemia after the MMT (nadir glucose <= 3.0 mmol/L [54 mg/dL]) with those with glucose >3 mmol/L (54 mg/dL) revealed a difference in both peak insulin (1138 versus 760 pmol/L; P = .042) and peak glucagon-like peptide-1 (182 versus 86 pmol/L; P = .016) concentrations. Conclusions: Patients with HS had lower nadir PG and higher insulin responses than NHS patients after MMT. Regarding PG, PG <= 3.0 mmol/L (54 mg/dL) was the best discriminator of having hypoglycemic symptoms after the MMT. However, high insulin level seems the most important predictor for having both biochemical and symptomatic hypoglycemia. (C) 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.