Postprandial hypoglycemia after gastric bypass surgery: from pathogenesis to diagnosis and treatment

Abstract

Purpose of review: The Roux-en-Y gastric bypass surgery (RYGB) improves glucose control in majority of patients with type 2 diabetes. However, a minority group of individuals develop a life-threatening complication of hyperinsulinemic hypoglycemia. The goal of this review is to identify underlying mechanisms by which RYGB cause hypoglycemia and describe pathogenesis-driven strategies to diagnose and treat this condition.

Recent findings: Gastric bypass leads to higher and earlier peak levels of glucose and lower nadir glucose after eating along with larger insulin and glucagon-like peptide 1 (GLP-1) secretion, resetting the balance between glucose appearance and clearance after this procedure. These weight-loss independent glycemic effects of RYGB have been attributed to changes in ingested glucose appearance as a result of rapid nutrient emptying from stomach pouch to the intestine and increased glucose clearance as a result of prandial hyperinsulinemia. The exaggerated effect of RYGB on postmeal glucose metabolism is a syndrome of postprandial hyperinsulinemic hypoglycemia manifesting in a group of individuals several years after this surgery. Affected patients have larger systemic appearance of ingested glucose and greater postmeal secretion of insulin and GLP-1 compared to those with history of RYGB without symptomatic hypoglycemia. Current evidence supporting a multifactorial model of glucose dysregulation among patients with hypoglycemia will be highlighted in this review.

Summary: Hypoglycemia after RYGB is a life-threatening condition and likely represents the extreme glycemic phenotype of this procedure. Diagnosis is challenging and treatment options are limited.

FIGURE 1.

Changes in glucose delivery and glucose utilization typical of gastric bypass surgery and the steps that are implicated in the pathogenesis of hypoglycemia after this procedure. The glycemic gradient across the liver contributing to enhanced net hepatic glucose uptake is shown by different font sizes in this figure. ^☆, Gastric bypass effect; ^☆, Pathophysiologic defect specific to hypoglycemia; ^★, Treatment options utilized based on pathogenic factors. CNS, central nervous system; GE, gastric emptying; GLP-1, glucagon-like peptide-1; IR, insulin receptor; S_G, glucose effectiveness.