Pancreatic alpha-cell function in idiopathic reactive hypoglycemia.Metabolism. 1997 Jun; 46(6):639-43.M
Idiopathic reactive hypoglycemia (IRH) is a well-documented but overdiagnosed syndrome. The presence of transient hypoglycemia and enhanced insulin secretion and/or increased insulin sensitivity before the onset of IRH is well documented. However, the data regarding glucagon secretion are sparse. Therefore, this study assessed glucagon and insulin responses to (1) oral ingestion of 100 g glucose oral glucose tolerance test (OGTT) and (2) a 100-g protein meal after an overnight fast in a randomized sequence at intervals of 7 to 10 days in five subjects with previously well-documented IRH and six normal subjects. Basal plasma glucose and insulin levels were not significantly different in both groups. However, basal glucagon was significantly higher (P < .025) in IRH subjects (347 +/- 83 ng/L) compared with normals (135 +/- 20 ng/L). In IRH subjects during the OGTT, hypoglycemia (2.7 +/- 0.11 mmol/L) occurred at 150 +/- 16 minutes and was preceded by a markedly higher (P < .01) peak glucose concentration (11.7 +/- 0.6 mmol/L) at 36 +/- 6 minutes in comparison to normals (8.8 +/- 0.4 mmol/L), indicating the presence of impaired glucose tolerance in these subjects. Similarly, the plasma insulin increase was significantly higher (P < .01) but delayed in IRH subjects compared with normals. In contrast, glucagon suppression was not significantly different in both groups, although glucagon failed to increase following hypoglycemia in IRH. During a protein meal, plasma glucose declined in both groups, with a significantly (P < .05) greater decrease in IRH subjects (-0.8 +/- 0.2 mmol/L) compared with normals (0.5 +/- 0.1 mmol/L). However, the glucagon increase was significantly (P < .01) blunted in IRH subjects (61% +/- 15%) in comparison to normals (152% +/- 39%). Thus, basal hyperglucagonemia with normal glucose concentration may suggest the presence of a hyposensitivity of the glucagon receptor in IRH. Moreover, the lack of appropriate suppression during the OGTT despite marked hyperglycemia, the lack of an increase at the onset of hypoglycemia, and the inhibited response to a protein meal in IRH subjects compared with normals denote altered glucagon secretion in IRH. Therefore, it is likely that glucagon receptor downregulation and impaired glucagon sensitivity and secretion may contribute to postprandial hypoglycemia in IRH.