Excessive circulating large molecular weight immunoreactive glucagon components in subjects with the idiopathic...

The glucagon RIA measures several molecular components in human plasma. Clinical disorders have been described associated with abnormal elevations of certain of these components. This report documents another clinical disorder, the idiopathic postprandial syndrome, which also appears associated with excessive circulating large molecular weight immunoreactive glucagon (IRG) components. During studies of glucose homeostasis in subjects with apparent idiopathic postabsorptive hypoglycemia, 80 subjects were evaluated using oral glucose tolerance tests; 18 subjects were found to have clinical and laboratory findings consistent with the disorder, and of these, 3 had markedly elevated basal total plasma IRG levels. Plasma IRG responses in the subjects after oral glucose or mixed meals were variable. Physical characterization of the excessive large molecular weight IRG components revealed molecular weight estimates of 300,000 and 345,000 daltons in 2 subjects and of more than 200,000 daltons in the third subject. The origin and chemical nature of this material is uncertain. None of these subjects had evidence for a glucagonoma, as supported by the virtual absence of detectable levels of native (3500-dalton) glucagon after gel filtration. Since the origin of the idiopathic postprandial syndrome as well as the origin and chemical nature of large molecular weight IRG components are unknown, the association of these two findings remains unclear but is clinically important in the differential diagnosis of the glucagonoma syndrome.