Background

Postprandial hyperinsulinemic hypoglycemia (PHH) after Roux-en-Y gastric bypass (RYGB) may involve a mismatch in timing and amount of post-meal glucose with insulin secretion. With ingestion of high carbohydrate load, exaggerated insulin release follows rise in post-meal glucose. Proposed mechanisms include decreased systemic and adipose inflammation, increased liver and muscle insulin receptor expression, and stimulation of pancreatic beta cell hyperplasia by incretins such as glucagon-like peptide-1 (GLP-1).Management includes acarbose, diazoxide, and octreotide; Exendin 9-39, a GLP-1 antagonist, is being studied. PHH is not fully understood; options to date have not proven reliably effective, leading some patients to RYGB reversal or even partial pancreatectomy, risking diabetes. Options posited to be of possible benefit in small and/or uncontrolled settings for PHH are GLP-1 receptor agonists, proposed to potentially improve matching efficiency between post-meal insulin secretion with glucose.

Methods

We conducted a pilot randomized placebo-controlled cross-over trial with baseline mixed meal tolerance tests to establish PHH followed by 3 blinded visits with either or both active 25mg acarbose and 5mcg exenatide, followed by final visit with open label 10mcg exenatide.

Results

Six women and 2 men, mean age 52.0 (SD:9.2) and BMI 32.2 (5.4) had mean peak glucose value of 187.5 (SD:46.9) and minimum glucose value of 51.8 (SD:3.9) at baseline visit.One of eight required hypoglycemia rescue at baseline visit and one with acarbose alone, compared to 3 with exenatide alone at 5mcg and 2 on 10mcg exenatide. Mean trough glucoses were 58.4 (12.9), 53.5 (16.4), 45.4 (10.5), and 42.9 (8.0) for acarbose, both agents, 5mcg exenatide, and 10mcg exenatide, respectively.

Conclusions

In summary, though this is a small study, results of this pilot trial suggest exenatide does not ameliorate PPH post RYGB; research is needed to better define underlying pathophysiology to inform potential treatments.