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Glucagon Responses to Hypoglycemia in Children and Adolescents With IDDM

To investigate plasma glucagon counterregulatory responses to hypoglycemia, an intravenous insulin bolus was given over 2 min to 73 children, aged 8.5–18.8 yr, with diabetes duration 1.2–17.1 yr. The plasma glucagon responses of the 61 children without glucagon antibodies or abnormal glucagon molecules were compared with those of 13 nondiabetic control subjects, aged 8.3–18.3 yr. Glucagon increments from baseline (73 ± 10 pg/ml) and peak glucagon responses (212 ± 13 pg/ml) were markedly lower in diabetic patients than in control subjects (341 ± 49 and 462 ± 51 pg/ml, respectively, P < .001). Glucagon responses were found to correlate positively with the age of the patients at the time of testing (r = .478, P < .001) and inversely with metabolic control as measured by glycosylated hemoglobin (r = −.342, P < .02). There was no relationship between glucagon responses and diabetes duration. There was also no relationship between the glucagon increments and free-insulin levels during the test. Glucose recovery from the nadir was impaired in diabetic subjects compared with control subjects and correlated inversely with free-insulin levels. However, glucose recovery did not correlate with the rise of plasma glucagon. Glucose recovery was not different in patients with glucagon antibodies. In this study, we have demonstrated a deficient glucagon response to hypoglycemia in children with insulin-dependent diabetes mellitus. However, the clinical significance of this deficit is not clear.