Gastric bypass (GB) alters postprandial glucose pattern with a higher peak of glucose and lower glucose nadir. Glycemic effects of GB is exaggerated in patients suffering from postprandial hyperinsulinemic hypoglycemia. Diagnosis is complex and requires documentation of concurrent symptoms with low glucose that are relieved by carbohydrate (CHO) intake (Whipple’s triad). Mixed meal tolerance test (MTT) is often used to provoke hypoglycemia but glucose threshold to fulfill Whipple’s triad remains unknown. Here we measured accuracy of 350-kcal MTT (Ensure Plus®, 51 g CHO) to diagnose hypoglycemia in 95 GB subject (43 with prior documented hypoglycemia [H] and 52 asymptomatic [A]). In addition, measured outcomes were compared with those during isovolemic 250-kcal liquid MTT (Ensure®, 40 g CHO) in a separate cohort of 49 GB subjects (31 H vs. 18 A). Time and weight loss since surgery, BMI, and A1c were similar between H and A. The H subjects had lower fasting glucose (80±1 vs. 84±1 mg/dL, P<0.05) and nadir glucose levels (51±2 vs. 67±2 mg/dL, P<0.001). Nadir glucose values were associated with fasting glucose (r=0.6, P<0.001). Plotting true positive rate (sensitivity) against false positive rates (1-specificity) for nadir glucose during MTT yielded an area under the Receiver Operating Characteristics (ROC) curve of 0.80±0.05. A nadir blood glucose cut-off of 53 mg/dL produced the highest sum of sensitivity (65%) and specificity (88%) for detecting hypoglycemia. Lower CHO ingestion (40 g) did not significantly affect the accuracy of MTT to diagnose hypoglycemia (AUC ROC: 0.69±0.08). Our findings indicates that mixed meals containing 40-50 g of CHO have good discriminatory value to diagnose hypoglycemia after GB using blood glucose threshold of <54mg/dL.


H. Honka: None. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. M.E. Patti: Consultant; Self; Eiger BioPharmaceuticals. Research Support; Self; Dexcom, Inc., Janssen Pharmaceuticals, Inc., MedImmune, Xeris Pharmaceuticals, Inc. M. Salehi: None.


National Institutes of Health (DK105379, DK083554 to M.S.); National Center for Advancing Translational Sciences (8UL1TR000077); Finnish Cultural Foundation (00180071)

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