Beta-cell sensitivity reduced after gastric bypass surgery

By Will Boggs MD

NEW YORK (Reuters Health) - 4/3/2019

After gastric bypass surgery, beta-cells in nondiabetic patients are less sensitive to insulinotropic gut hormones, researchers report.

"Prior to our report, evidence suggested that postprandial beta-cell sensitivity to glucose and glucagon-like peptide 1 (GLP-1) contribution to hyperinsulinemia is increased after Roux-en-Y gastric bypass (RYGB)," said Dr. Marzieh Salehi of the University of Cincinnati College of Medicine and the University of Texas at San Antonio.

"Our findings portray a completely different model of surgical effects on beta-cell function. In nondiabetic individuals several years after surgery, beta-cell sensitivity to glucose and insulinotropic gut hormones, GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) are substantially reduced in the absence of meal stimulation," she told Reuters Health by email.

Earlier, Dr. Salehi's team found that beta-cell sensitivity to graded doses of intravenous glucose is diminished in nondiabetic individuals after gastric bypass, compared with non-operated matched controls.

In the current study, they tested their hypothesis that individuals with gastric bypass (GB) would also have reduced insulin responses to exogenous GLP-1 and GIP in 10 patients with a history of GB and nine age- and BMI-matched controls without diabetes and with no history of gastrointestinal surgeries.

Fasting levels of insulin and insulin secretion rates were significantly lower in GB patients than in controls. After intravenous glucose administration, both early-phase insulin response (0-10 minutes) and second-phase insulin secretion (70-90 minutes) were lower in GB patients than in controls.

Insulin clearance during fasting tended to be higher in the GB patients, while during the glucose clamp studies, insulin clearance was twofold to threefold greater in GB subjects than in controls, the team reports Gut, online February 16.

During fixed hyperglycemia, the stepwise increase of GLP-1 dose-dependently raised insulin secretion, but insulin responses to both GLP-1 and GIP infusions were significantly lower in GB patients than in controls.

Beta-cell sensitivity to these incretins was significantly lower in GB patients than in controls, even after adjustment for insulin sensitivity.

"Postprandial hyperinsulinemia after GB is mainly caused by enhanced meal-stimulated GLP-1 secretion (20-fold compared to non-operated) and increased gastric delivery of glucose to the gut (25-fold compared to non-operated)," Dr. Salehi said. "It remains to be examined whether variation in blunted beta-cell responsiveness in the setting of GI surgery contributes to deterioration in glucose tolerance over time (diabetes relapse after surgery) or once augmented enteral stimulation is removed (reversal of RYGB)."

"Understanding the mechanisms connecting surgical changes in the gut and beta-cell function has potential benefits for development of novel approaches for treatment of diabetes as well as improvement of glycemia effects of RYGB in patients with partial diabetes or relapse after complete remission as well as those with hyperinsulinemic hypoglycemia syndrome," she said.

Dr. Jean Buteau from Alberta Diabetes Institute, in Edmonton, Canada, who recently found evidence of beta-cell proliferation and neogenesis in a patient with hyperinsulinemic hypoglycemia after GB, told Reuters Health by email, "These results contrast with those of a previous study that examined a similar question but at earlier time points (1 week and 3 months post-operation)."

In that study (, he added, "Dirksen and colleagues demonstrated that exaggerated release and preserved incretin action provoked insulin hypersecretion after bariatric surgery. To reconcile the two studies, we could posit that this adaptive mechanism is long-term and develops slowly over the course of several months."

"It would be interesting to test if this adaptive mechanism fails in subjects with hyperinsulinemic hypoglycemia," said Dr. Buteau, who was not involved in the new work.


Gut 2019.

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