Preventing Hypoglycemia After Gastric Bypass

Many patients who undergo gastric bypass surgery experience hypoglycemia after meals. Researchers report in the March issue of Gastroenterology that they can correct this condition with an agent that blocks the receptor for the glucagon-like peptide 1 (GLP1).

Roux-en-Y gastric bypass surgery, widely used to treat obesity, alters glucose metabolism in some individuals. Although the procedure provides many benefits, some patients experience high levels of insulin and low levels of blood sugar after meals (postprandial hyperinsulinemic hypoglycemia). This can lead to palpitations, lightheadedness, sweating, confusion, decreased attentiveness, and even seizures or loss of consciousness. In the patients who experience these symptoms, they occur within 1–3 hours after meals—particularly those rich in simple carbohydrates.

Although multiple mechanisms are likely to contribute to this form of hypoglycemia, several studies have indicated a role for increased levels of GLP1, which is released from intestinal L-cells in response to meals. GLP1 binds to receptors on beta cells to stimulate insulin secretion in a glucose-dependent manner. Postprandial levels of GLP1 were reported to increase more than 10-fold in patients who underwent bypass surgery.

Marzieh Salehi et al. investigated whether a blocker of the GLP1 receptor, called exendin (9–39), affected hyperinsulinemic hypoglycemia after gastric bypass. Their clinical trial included 9 patients with recurrent hypoglycemia after gastric bypass, 7 patients who were asymptomatic after gastric bypass, and 8 healthy individuals (controls). The subjects ate the same meal, and their glucose was traced.

Salehi et al. found that infusion of exendin (9–39) corrected glycemia in all patients with recurrent hypoglycemia after gastric bypass, reducing postprandial insulin secretion by 50%. In comparison, postprandial insulin secretion was reduced by only 13% in subjects who were asymptomatic after gastric bypass and 14% in controls.

Exendin (9–39) also increased the rate at which meal-derived glucose increased in hypoglycemic patients, compared with controls, whereas hepatic glucose production did not differ significantly between groups.

In an editorial that accompanies the article, Mary-Elizabeth Patti and Allison Goldfine say that the disproportionately greater response to exendin (9–39) among patients with hypoglycemia syndrome indicates that GLP1 contributes to their excessive insulin secretion and hypoglycemia after meals.

Patti and Goldfine propose that post-bypass hyperinsulinemic hypoglycemia arises from changes that the surgery and its associated weight loss produce in glycemic and hormonal patterns after meals (see figure).

Potential mechanism by which exendin(9–39) reduces GLP1 signaling, insulin secretion, and hypoglycemia in patients with gastric bypass.

Potential mechanism by which exendin(9–39) reduces GLP1 signaling, insulin secretion, and hypoglycemia in patients with gastric bypass.

Following gastric bypass, food intake and rapid emptying of the gastric pouch lead to excessive increases in glucose and parallel increases in insulin secretion, with subsequent rapid decreases in glucose levels.

Salehi et al. add that the distinct pattern of ingested glucose appearance among subjects with recurrent hypoglycemia after gastric bypass indicates that altered gastrointestinal function contributes to glucose abnormalities in this syndrome. They say that larger studies are needed to determine if these findings are applicable to a broad range of subjects who have undergone gastric bypass.

About Kristine Novak, PhD, Science Editor

Dr. Kristine Novak is the science editor for Gastroenterology and Clinical Gastroenterology and Hepatology, both published by the American Gastroenterological Association. She has worked as an editor at biomedical research journals and as a science writer for more than 12 years, covering advances in gastroenterology, hepatology, cancer, immunology, biotechnology, molecular genetics, and clinical trials. She has a PhD in cell biology and an interest in all areas of medical research.
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One Response to Preventing Hypoglycemia After Gastric Bypass

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