European Journal of Pediatrics

, Volume 167, Issue 8, pp 859–865 | Cite as

Fasting adaptation in idiopathic ketotic hypoglycemia: a mismatch between glucose production and demand

  • Hidde H. Huidekoper
  • Marinus Duran
  • Marjolein Turkenburg
  • Mariëtte T. Ackermans
  • Hans P. Sauerwein
  • Frits A. Wijburg
Original Paper


In order to study the pathophysiology of hypoglycemia in idiopathic ketotic hypoglycemia (KH), glucose kinetics during fasting in patients with KH were determined. A fasting test was performed in 12 children with previously documented KH. Besides determination of glucoregulatory hormones, plasma ketones, FFA and alanine, the rates of endogenous glucose production (EGP), glucose uptake, gluconeogenesis (GNG) and glycogenolysis (GGL) were quantified using the [6,6-2H2] glucose isotope dilution method and the deuterated water method. The five youngest subjects (age 2.5–3.9 years) became hypoglycemic (glucose <3.0 mmol/l) during the test. Mean differences in glucose kinetics between overnight fasting and the end of the test in the hypoglycemic vs. the normoglycemic subjects were: EGP: −31.9% vs. −17.9% (p = 0.007), GGL: −66.2% vs. −50.8% (p = 0.465) and GNG 6.8% vs. 19.5% (p = 0.465). Plasma alanine levels were significantly lower (p = 0.028) at the end of the test in the hypoglycemic subjects. Plasma ketones and FFA levels were in the normal range for fasting duration in all subjects. We conclude that hypoglycemia in KH is caused by the inability to sustain an adequate EGP during fasting in view of the higher glucose requirement in young children. The decrease in GGL is not accompanied by a significant increase in GNG, possibly because of a limitation in the supply of alanine. Our results support the hypothesis that KH represents the lower tail of the Gaussian distribution of fasting tolerance in children.


Endogenous glucose production Glucose kinetics Children Stable isotope Toddlers’ hypoglycemia 



ketotic hypoglycemia


endogenous glucose production

Ra glucose

rate of appearance of glucose in plasma

Rd glucose

rate of disappearance of glucose from plasma


rate of appearance of glucose from gluconeogenesis in plasma


rate of appearance of glucose from glycogenolysis in plasma


glycogen storage disease type 0


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Hidde H. Huidekoper
    • 1
  • Marinus Duran
    • 1
    • 2
  • Marjolein Turkenburg
    • 2
  • Mariëtte T. Ackermans
    • 3
  • Hans P. Sauerwein
    • 4
  • Frits A. Wijburg
    • 1
  1. 1.Department of Pediatrics (G8-205)Academic Medical Center, University of AmsterdamAmsterdamThe Netherlands
  2. 2.Department of Clinical Chemistry, Laboratory Genetic Metabolic DiseasesAcademic Medical Center, University of AmsterdamAmsterdamThe Netherlands
  3. 3.Department of Clinical Chemistry, Laboratory for Endocrinology and RadiochemistryAcademic Medical Center, University of AmsterdamAmsterdamThe Netherlands
  4. 4.Department of Endocrinology and MetabolismAcademic Medical Center, University of AmsterdamAmsterdamThe Netherlands

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