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Hyperinsulinemic Hypoglycemia After Gastric Bypass Surgery Is Not Accompanied by Islet Hyperplasia or Increased ß-Cell Turnover

Larry Hillblom Islet Research Center, UCLA David Geffen School of Medicine, Los Angeles, California

Address correspondence and reprint requests to Peter C. Butler, Larry Hillblom Islet Research Center, UCLA David Geffen School of Medicine, 24-130 Warren Hall, 900 Veteran Ave., Los Angeles, CA 90095-7073. E-mail: pbutler{at}mednet.ucla.edu

OBJECTIVE—The purpose of this study was to establish whether hypoglycemia after gastric bypass surgery (GBS) for morbid obesity is due to increased fractional ß-cell area or inappropriately increased insulin secretion.

RESEARCH DESIGN AND METHODS—We examined pancreata obtained at partial pancreatectomy from 6 patients with post-GBS hypoglycemia and compared these with 31 pancreata from obese subjects and 16 pancreata from lean control subjects obtained at autopsy. We addressed the following questions. In patients with post-GBS hypoglycemia, is ß-cell area increased and is ß-cell formation increased or ß-cell apoptosis decreased?

RESULTS—We report that in patients with post-GBS hypoglycemia, ß-cell area was not increased compared with that in obese or even lean control subjects. Consistent with this finding, there was no evidence of increased ß-cell formation (islet neogenesis and ß-cell replication) or decreased ß-cell loss in patients with post-GBS hypoglycemia. In control subjects, mean ß-cell nuclear diameter correlated with BMI (r² = 0.79, P < 0.001). In patients with post-GBS hypoglycemia, ß-cell nuclear diameter was increased (P < 0.001) compared with that for BMI in matched control subjects but was appropriate for BMI before surgery.

CONCLUSIONS—We conclude that post-GBS hypoglycemia is not due to increases in ß-cell mass or formation. Rather, postprandial hypoglycemia after GBS is due to a combination of gastric dumping and inappropriately increased insulin secretion, either as a failure to adaptively decrease insulin secretion after GBS or as an acquired phenomenon.

Abbreviations: GBS, gastric bypass surgery • GLP-1, glucagon-like peptide 1

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