Glucose and leucine kinetics in idiopathic ketotic hypoglycaemia

Aims: To investigate glucose and leucine kinetics in association with metabolic and endocrine investigations in children with ketotic hypoglycaemia (KH) in order to elucidate the underlying pathophysiology. Methods: Prospective interventional study using stable isotope tracer in nine children (mean age 4.23 years, range 0.9 - 9.8 years; seven males) with KH and 11 controls (mean age 4.57 years, range 0.16 - 12.3 years; four males). Results: Plasma insulin levels were significantly lower in KH compared to subjects in the non-KH group. Plasma ketone body levels were significantly higher in KH than in non-KH. Basal metabolic rate was significantly higher in subjects with KH (45.48 +/- 7.41 v 31.81 +/- 6.72 kcal/kg/day) but the respiratory quotients were similar in both groups (KH v non-KH, 0.84 +/- 0.05 v 0.8 +/- 0.04). Leucine oxidation rates were significantly lower in children with KH (12.25 +/- 6.25 v 31.96 +/- 8.59 mu mol/kg/h). Hepatic glucose production rates were also significantly lower in KH (3.84 +/- 0.46 v 6.6 +/- 0.59 mg/kg/min). Conclusions: KH is caused by a failure to sustain hepatic glucose production rather than by increased glucose oxidation rates. Energy demand is significantly increased, whereas leucine oxidation is reduced.