Hypoglycemia After Gastric Bypass Surgery: Current Concepts and Controversies

Abstract

Context: Hypoglycemia, occurring after bariatric and other forms of upper gastrointestinal surgery, is increasingly encountered by clinical endocrinologists. The true frequency of this condition remains uncertain, due, in part, to differences in the diagnostic criteria and in the affected populations, as well as relative lack of patient and physician awareness and understanding of this condition. Postbariatric hypoglycemia can be severe and disabling for some patients, with neuroglycopenia (altered cognition, seizures, and loss of consciousness) leading to falls, motor vehicle accidents, and job and income loss. Moreover, repeated episodes of hypoglycemia can result in hypoglycemia unawareness, further impairing safety and requiring the assistance of others to treat hypoglycemia.

Objective: In this review, we summarize and integrate data from studies of patients affected by hypoglycemia after Roux-en-Y gastric bypass (RYGB) surgery, obtained from PubMed searches (1990 to 2017) and reference searches of relevant retrieved articles. Whereas hypoglycemia can also be observed after sleeve gastrectomy and fundoplication, this review is focused on post-RYGB, given the greater body of published clinical studies at present.

Outcome measures: Data addressing specific aspects of diagnosis, pathophysiology, and treatment were reviewed by the authors; when not available, the authors have provided opinions based on clinical experience with this challenging condition.

Conclusions: Hypoglycemia, occurring after gastric bypass surgery, is challenging for patients and physicians alike. This review provides a systematic approach to diagnosis and treatment based on the underlying pathophysiology.

Figure 1.

Typical glycemic and hormonal patterns in the fasting state and after mixed meal. (A) Blood glucose, (B) plasma insulin, and (C) insulin secretory response (ISR) to meal ingestion. (D) Systemic appearance of ingested glucose (Ra_Oral) and (E) circulating glucagon-like peptide 1 (GLP-1) levels during meal tolerance test in RYGB subjects with (black ● and solid line) and without (black ○ and dashed line) hypoglycemia and nonsurgical controls (gray ▪ and solid line). Reproduced from Salehi et al. (6, 10).

Figure 2.

Suggested approach to possible hypoglycemia in a postbariatric patient. glc, glucose.

Figure 3.

Potential contributors to the pathophysiology of PBH. Shown is anatomy following RYGB. Contributing factors include the following: (1) accelerated nutrient emptying from stomach pouch to intestine (roux limb), leading to increased rate of appearance of glucose into blood and increased peak postprandial glucose; (2) enhanced enteroinsulin axis activity, with increased secretion and action of GLP-1 and possible direct nutrient effects and neural factors; (3) postprandial hyperinsulinemia, resulting from increased β-cell glucose sensitivity with increased glucose, cessation of β-cell secretion during decreasing glycemia, decreased insulin clearance, increased portal-systemic gradient for postmeal glucose, and GLP-1, with potential heterogeneity of β-cell mass; and (4) noninsulin-dependent factors, with reduced counter-regulatory hormone response (e.g., glucagon), increased glucose effectiveness (noninsulin-dependent glucose uptake), and gut mucosal adaptations (altering nutrient absorption, bile acid uptake and metabolism, and microbiome).

Figure 4.

Suggested approach to the treatment of established post-RYGB hypoglycemia.