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

Abstract

OBJECTIVE—The purpose of this study was to establish whether hypoglycemia after gastric bypass surgery (GBS) for morbid obesity is due to increased fractional β-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 β-cell area increased and is β-cell formation increased or β-cell apoptosis decreased? RESULTS—We report that in patients with post-GBS hypoglycemia, β-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 β-cell formation (islet neogenesis and β-cell replication) or decreased β-cell loss in patients with post-GBS hypoglycemia. In control subjects, mean β-cell nuclear diameter correlated with BMI (r2 = 0.79, P < 0.001). In patients with post-GBS hypoglycemia, β-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 β-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.