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Approach to hypoglycemia in infants and children

Agneta Sunehag, MD, PhD
Morey W Haymond, MD
Section Editor
Joseph I Wolfsdorf, MB, BCh
Deputy Editor
Alison G Hoppin, MD


In healthy individuals, maintenance of a normal plasma glucose concentration depends upon:

A normal endocrine system for integrating and modulating substrate mobilization, interconversion, and utilization.

Functionally intact enzymes for glycogen synthesis, glycogenolysis, glycolysis, gluconeogenesis, and utilization of other metabolic fuels for oxidation and storage.

An adequate supply of endogenous fat, glycogen, and potential gluconeogenic substrates (eg, amino acids, glycerol, and lactate).

Adults are capable of maintaining a near-normal plasma glucose concentration, even when fasting for weeks or, in the case of obese subjects, months [1]. In contrast, healthy neonates and young children are unable to maintain normal plasma glucose concentrations after even a short fast (24 to 36 hours) and exhibit a progressive decline in plasma glucose concentration to hypoglycemic values [2,3].

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Literature review current through: Nov 2017. | This topic last updated: Oct 18, 2016.
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  1. Cahill GF Jr, Herrera MG, Morgan AP, et al. Hormone-fuel interrelationships during fasting. J Clin Invest 1966; 45:1751.
  2. Chaussain JL, Georges P, Calzada L, Job JC. Glycemic response to 24-hour fast in normal children: III. Influence of age. J Pediatr 1977; 91:711.
  3. Haymond MW, Karl IE, Clarke WL, et al. Differences in circulating gluconeogenic substrates during short-term fasting in men, women, and children. Metabolism 1982; 31:33.
  4. Darmaun D, Haymond MW, Bier DM. Metabolic aspects of fuel homeostasis in the fetus and neonate. In: Endocrinology, 3rd ed, DeGroot LJ, Besser M, Burger HG, et al (Eds), WB Saunders, Philadelphia 1995. p.2258.
  5. Kalhan SC, D'Angelo LJ, Savin SM, Adam PA. Glucose production in pregnant women at term gestation. Sources of glucose for human fetus. J Clin Invest 1979; 63:388.
  6. Sunehag A, Ewald U, Gustafsson J. Extremely preterm infants (< 28 weeks) are capable of gluconeogenesis from glycerol on their first day of life. Pediatr Res 1996; 40:553.
  7. Grajwer LA, Sperling MA, Sack J, Fisher DA. Possible mechanisms and significance of the neonatal surge in glucagon secretion: studies in newborn lambs. Pediatr Res 1977; 11:833.
  8. Cornblath M, Schwartz R. Disorders of Carbohydrate Metabolism in Infancy, Blackwell Publications, Cambridge, MA 1991.
  9. Haymond MW, Sunehag A. Controlling the sugar bowl. Regulation of glucose homeostasis in children. Endocrinol Metab Clin North Am 1999; 28:663.
  10. Haymond MW, Howard C, Ben-Galim E, DeVivo DC. Effects of ketosis on glucose flux in children and adults. Am J Physiol 1983; 245:E373.
  11. Bier DM, Leake RD, Haymond MW, et al. Measurement of "true" glucose production rates in infancy and childhood with 6,6-dideuteroglucose. Diabetes 1977; 26:1016.
  12. Huopio H, Shyng SL, Otonkoski T, Nichols CG. K(ATP) channels and insulin secretion disorders. Am J Physiol Endocrinol Metab 2002; 283:E207.
  13. Amiel SA, Simonson DC, Sherwin RS, et al. Exaggerated epinephrine responses to hypoglycemia in normal and insulin-dependent diabetic children. J Pediatr 1987; 110:832.
  14. Cryer PE. Banting Lecture. Hypoglycemia: the limiting factor in the management of IDDM. Diabetes 1994; 43:1378.
  15. Thornton PS, Stanley CA, De Leon DD, et al. Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children. J Pediatr 2015; 167:238.
  16. Holtkamp HC, Verhoef NJ, Leijnse B. The difference between the glucose concentrations in plasma and whole blood. Clin Chim Acta 1975; 59:41.
  17. Geeting DG, Suther CA, Sylbert P. Determination of glucose in serum and whole blood: statistical relationships between values obtained by different methods. Clin Chem 1972; 18:976.
  18. Collier A, Steedman DJ, Patrick AW, et al. Comparison of intravenous glucagon and dextrose in treatment of severe hypoglycemia in an accident and emergency department. Diabetes Care 1987; 10:712.
  19. Wiethop BV, Cryer PE. Alanine and terbutaline in treatment of hypoglycemia in IDDM. Diabetes Care 1993; 16:1131.
  20. Llamado R, Czaja A, Stence N, Davidson J. Continuous octreotide infusion for sulfonylurea-induced hypoglycemia in a toddler. J Emerg Med 2013; 45:e209.
  21. Chung ST, Haymond MW. Minimizing morbidity of hypoglycemia in diabetes: a review of mini-dose glucagon. J Diabetes Sci Technol 2015; 9:44.
  22. Haymond MW. Hypoglycemia in infants and children. Endocrinol Metab Clin North Am 1989; 18:211.
  23. Verrotti A, Fusilli P, Pallotta R, et al. Hypoglycemia in childhood: a clinical approach. J Pediatr Endocrinol Metab 1998; 11 Suppl 1:147.
  24. Stanley CA, Lieu YK, Hsu BY, et al. Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. N Engl J Med 1998; 338:1352.
  25. Roe TF, Kogut MD. Hypopituitarism and ketotic hypoglycemia. Am J Dis Child 1971; 121:296.
  26. Kershnar AK, Roe TF, Kogut MD. Adrenocorticotropic hormone unresponsiveness: report of a girl with excessive growth and review of 16 reported cases. J Pediatr 1972; 80:610.
  27. Morris AA, Thekekara A, Wilks Z, et al. Evaluation of fasts for investigating hypoglycaemia or suspected metabolic disease. Arch Dis Child 1996; 75:115.
  28. Green RP, Hollander AS, Thevis M, et al. Detection of surreptitious administration of analog insulin to an 8-week-old infant. Pediatrics 2010; 125:e1236.
  29. Ferrara C, Patel P, Becker S, et al. Biomarkers of Insulin for the Diagnosis of Hyperinsulinemic Hypoglycemia in Infants and Children. J Pediatr 2016; 168:212.
  30. Clayton PT, Eaton S, Aynsley-Green A, et al. Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion. J Clin Invest 2001; 108:457.
  31. Binkiewicz A, Senior B. Decreased ketogenesis in von Gierke's disease (type I glycogenosis). J Pediatr 1973; 83:973.
  32. Fernandes J, Pikaar NA. Ketosis in hepatic glycogenosis. Arch Dis Child 1972; 47:41.
  33. Cornblath M, Pildes RS, Schwartz R. Hypoglycemia in infancy and childhood. J Pediatr 1973; 83:692.
  34. van Hasselt PM, Ferdinandusse S, Monroe GR, et al. Monocarboxylate transporter 1 deficiency and ketone utilization. N Engl J Med 2014; 371:1900.