OBJECTIVE -The purpose of this study was to establish whether hypoglycemia after gastric bypass surgery (GBS) for morbid obesity is due to increased fractional â€-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 â€-cell area increased and is â€-cell formation increased or â€-cell apoptosis decreased?RESULTS -We report that in patients with post-GBS hypoglycemia, â€-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 â€-cell formation (islet neogenesis and â€-cell replication) or decreased â€-cell loss in patients with post-GBS hypoglycemia. In control subjects, mean â€-cell nuclear diameter correlated with BMI (r 2 Ï 0.79, P Ïœ 0.001). In patients with post-GBS hypoglycemia, â€-cell nuclear diameter was increased (P Ïœ 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 â€-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.
Diabetes Care 29:1554 -1559, 2006G astric bypass surgery (GBS) is a common therapy for patients with morbid obesity (1). Recently, Service et al. (2) reported six patients with postprandial hyperinsulinemic hypoglycemia that developed after Roux-en-Y GBS. The largest islet size was greater in these patients compared with that in control subjects with pancreatic cancer. Also, insulin-staining cells were noted related to exocrine ducts. Together these findings were interpreted as consistent with nesidioblastosis (2). Three additional patients presenting with similar clinical symptoms and presumed increased new islet formation were subsequently reported by Patti et al. (3,4). These reports prompted speculation that increased secretion of gastrointestinal hormones, such as glucagonlike peptide 1 (GLP-1), consequent to GBS might have led to increased â€-cell mass as a result of increased â€-cell formation. It was therefore proposed that the hyperinsulinemic hypoglycemia was likely secondary to this presumed excessive concentration of GLP-1 (5). In support, in vitro and animal studies reported that GLP-1 may increase â€-cell replication and inhibit â€-cell apoptosis (6,7), and it has been reported that GLP-1 concentrations are increased after GBS (8 -10).Hyperinsulinemic hypoglycemia has been reported both in infants (11,12) and more rarely in adults (13,14) in the absence of insulinoma. In infants, this condition was originally termed nesidioblast...