Glucagon secretion in unaffected monozygotic twins of juvenile diabetics

Glucagon secretion during a 50-g oral glucose tolerance test has been investigated in 16 nondiabetic monozygotic twins of juvenile diabetics and compared with the results in 10 normal controls and 10 untreated, newly diagnosed, maturity-onset diabetics. Normal subjects showed a significant mean fall in glucagon at 15, 30, and 60 min, with a return to the baseline at 120 min. Maturity-onset diabetics showed a significant mean rise 15 min after oral glucose. The mean of the twin group was intermediate between normals and diabetics, although there was considerable individual variation with some showing suppression and others stimulation of glucagon release. When the twins were divided according to the length of discordance it was found that the mean response in the 8 twins who had been discordant for a mean of 19 years was indistinguishable from that of normal subjects, whereas the mean response of twins discordant for a mean of only 4.5 years was similar to that of the diabetic patients. It is possible, therefore, that hypersecretion of glucagon may occur in some subjects predisposed to develop diabetes mellitus, and the finding of lack of suppression of glucagon in the identical twin of a juvenile diabetic may be of prognostic significance. Identical twins who have been discordant for over 10 years are thought on other grounds to be unlikely to develop diabetes, and the finding of a normal glucagon response is further confirmation of their normal metabolic status and reinforces the suggestion that they are not prediabetic.