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.