Defining clinically important hypoglycemia in patients with postbariatric hypoglycemia

Background: Postbariatric hypoglycemia (PBH) is a rare but growing complication of bariatric surgery. Many aspects have yet to be established, including the blood glucose threshold which represents clinically important hypoglycemia in affected patients.

Objective: To confirm the glucose threshold below which neuroglycopenic (NG) symptoms arise in patients with PBH during provoked and real-world hypoglycemia as an indicator of clinically important hypoglycemia.

Setting: Stanford University School of Medicine.

Methods: Forty patients with PBH were enrolled. Thirty-two patients underwent hypoglycemia provocation in the clinical research unit (CRU) during which symptoms and blood glucose concentrations were assessed. A sensitivity analysis and stepwise linear regression were conducted evaluating relationships between symptoms and glucose levels. To validate CRU findings in the real-world setting, 8 sex-, age-, body mass index (BMI)-, and disease severity-matched patients underwent 20 days of at-home continuous glucose monitoring (CGM), self-monitoring of blood glucose (SMBG), and symptom assessment by electronic diary (eDiary).

Results: In response to hypoglycemia provocation 19%, 59%, and 22% of patients developed a postprandial glucose nadir <70-54 mg/dL , <54-40 mg/dL, and <40 mg/dL, respectively. Number of NG symptoms was highest when glucose was in the <54-40 mg/dL range, although 23% of those with NG symptoms in this range, and 37% with NG symptoms below this range lacked autonomic symptoms, indicating substantial hypoglycemia unawareness. Sensitivity of symptoms to detect hypoglycemia was poor other than for drowsiness, while specificity was high for all NG symptoms. Confusion, sweating, drowsiness, and incoordination were significant independent predictors of hypoglycemia. Events captured during real-world monitoring mirrored CRU data, showing a spike in NG symptoms in the <54-40 mg/dL range. CGM captured up to 10-fold more events than were patient-perceived and captured by SMBG/eDiary.

Conclusion: Due to the peak in NG symptoms at glucose <54-40 mg/dL during provoked and real-world hypoglycemia, the low sensitivity/high specificity of NG symptoms to detect hypoglycemia, and high prevalence of hypoglycemia unawareness at glucose values <54 mg/dL, we propose that blood glucose <54 mg/dL should be taken to signify clinically important hypoglycemia in patients with established PBH.