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

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Abstract

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.

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Abbreviations

KH:

ketotic hypoglycemia

EGP:

endogenous glucose production

Ra glucose:

rate of appearance of glucose in plasma

Rd glucose:

rate of disappearance of glucose from plasma

GNG:

rate of appearance of glucose from gluconeogenesis in plasma

GGL:

rate of appearance of glucose from glycogenolysis in plasma

GSD-0:

glycogen storage disease type 0

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Acknowledgements

We would like to thank Thessa Westphal for technical assistance with the experiments, and An Ruiter and Barbara Voermans for their excellent analytical support.

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Authors and Affiliations

  1. Department of Pediatrics (G8-205), Academic Medical Center, University of Amsterdam, P.O. Box 22660, NL-1100 DD, Amsterdam, The Netherlands

    Hidde H. Huidekoper, Marinus Duran & Frits A. Wijburg

  2. Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Marinus Duran & Marjolein Turkenburg

  3. Department of Clinical Chemistry, Laboratory for Endocrinology and Radiochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Mariëtte T. Ackermans

  4. Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Hans P. Sauerwein

Authors
  1. Hidde H. Huidekoper
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  2. Marinus Duran
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  4. Mariëtte T. Ackermans
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Correspondence to Frits A. Wijburg.

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Huidekoper, H.H., Duran, M., Turkenburg, M. et al. Fasting adaptation in idiopathic ketotic hypoglycemia: a mismatch between glucose production and demand. Eur J Pediatr 167, 859–865 (2008). https://doi.org/10.1007/s00431-007-0598-5

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  • DOI: https://doi.org/10.1007/s00431-007-0598-5

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