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

Hidde H Huidekoper1, Marinus Duran, Marjolein Turkenburg

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

European Journal of Pediatrics
|October 16, 2007
PubMed

Insights

Children with ketotic hypoglycemia (KH) cannot adequately produce glucose during fasting due to insufficient endogenous glucose production (EGP). This inability, potentially linked to low alanine levels, causes hypoglycemia in young children with KH.

Area of Science:

  • Pediatrics
  • Endocrinology
  • Metabolic Disorders

Background:

  • Idiopathic ketotic hypoglycemia (KH) is a condition affecting children, characterized by low blood glucose levels during fasting.
  • Understanding the underlying pathophysiology of KH is crucial for effective management and treatment strategies.
  • Glucose metabolism during fasting plays a critical role in maintaining normoglycemia, especially in young children.

Purpose of the Study:

  • To investigate the glucose kinetics and pathophysiology of hypoglycemia in children with idiopathic ketotic hypoglycemia (KH).
  • To quantify endogenous glucose production (EGP), glucose uptake, gluconeogenesis (GNG), and glycogenolysis (GGL) during fasting in KH patients.
  • To explore the role of glucoregulatory hormones, ketones, free fatty acids (FFA), and alanine in the development of hypoglycemia.

Main Methods:

  • A fasting test was conducted on 12 children with a history of KH.
  • Glucose kinetics were measured using the [6,6-(2)H(2)] glucose isotope dilution method and the deuterated water method.
  • Measurements included glucoregulatory hormones, plasma ketones, FFA, alanine, EGP, glucose uptake, GNG, and GGL.

Main Results:

  • Five youngest subjects (2.5-3.9 years) developed hypoglycemia (glucose <3.0 mmol/l) during the test.
  • Hypoglycemic subjects showed significantly reduced endogenous glucose production (EGP) compared to normoglycemic subjects (-31.9% vs. -17.9%, p=0.007).
  • Lower plasma alanine levels were observed in hypoglycemic subjects at the end of the test (p=0.028), while GNG did not compensate for decreased GGL.

Conclusions:

  • Hypoglycemia in KH is attributed to an impaired ability to sustain adequate EGP in young children with higher glucose demands.
  • A potential limitation in alanine supply may hinder gluconeogenesis (GNG) to compensate for reduced glycogenolysis (GGL).
  • KH likely represents the lower extreme of normal fasting tolerance distribution in children.

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