Postprandial and postabsorptive
glucose metabolism was studied in a 3-yr-old girl with
leprechaunism by substrate and hormonal measurements and by quantifying hepatic
glucose output during continuous infusion of D-[6-6-2H2]-
glucose. Hepatic glucogen content and the activity of
glycogen synthase and
phosphorylase were also measured in the post-prandial state on a separate occasion. During the 4-h postprandial state, plasma
glucose,
alanine,
lactate,
beta-hydroxybutyrate, and
glycerol were normal, as were
hepatic glycogen,
glycogen synthase,
phosphorylase, and hepatic
glucose output of 7.5 mg kg-1 min-1.
Intravenous injection of
glucagon (30 micrograms kg-1) caused an immediate almost 3-fold rise in
glucose production consistent with brisk glycogenolysis. During the 8- to 12-h postabsorptive state, however, the patient had elevated levels of
glycerol (330-508 microM) and
beta-hydroxybutyrate (3291-3801 microM) and decreased levels of
glucose 24-29 mg/dl) and
alanine (121-135 microM) consistent with a much longer period of fasting in the normal child. Furthermore, hepatic
glucose output was reduced to 3.9 mg kg-1 min-1, and iv
glucagon injection failed to increase this rate; both of these observations are consistent with a hepatic state generally found only later in fasting in the normal child. From these observations we conclude that the
hypoglycemia reported in the
leprechaunism syndrome is due to an accelerated fasting state secondary to
insulin resistance. As with long-fasted,
glycogen-depleted normal children, gluconeogenesis alone is often not capable of adequately meeting the child's large noninsulin-dependent cerebral
glucose requirements.