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.
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.
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.
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.