Approach to hypoglycemia in infants and children
- Agneta Sunehag, MD, PhD
Agneta Sunehag, MD, PhD
- Associate Professor of Pediatrics
- Baylor College of Medicine
- Morey W Haymond, MD
Morey W Haymond, MD
- Professor of Pediatric Nutrition
- Baylor College of Medicine
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 glycogenolysis, glycogen synthesis, 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 . 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].
- Cahill GF Jr, Herrera MG, Morgan AP, et al. Hormone-fuel interrelationships during fasting. J Clin Invest 1966; 45:1751.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Cornblath M, Schwartz R. Disorders of Carbohydrate Metabolism in Infancy, Blackwell Publications, Cambridge, MA 1991.
- Haymond MW, Sunehag A. Controlling the sugar bowl. Regulation of glucose homeostasis in children. Endocrinol Metab Clin North Am 1999; 28:663.
- 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.
- 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.
- Huopio H, Shyng SL, Otonkoski T, Nichols CG. K(ATP) channels and insulin secretion disorders. Am J Physiol Endocrinol Metab 2002; 283:E207.
- 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.
- Cryer PE. Banting Lecture. Hypoglycemia: the limiting factor in the management of IDDM. Diabetes 1994; 43:1378.
- Holtkamp HC, Verhoef NJ, Leijnse B. The difference between the glucose concentrations in plasma and whole blood. Clin Chim Acta 1975; 59:41.
- 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.
- 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.
- Wiethop BV, Cryer PE. Alanine and terbutaline in treatment of hypoglycemia in IDDM. Diabetes Care 1993; 16:1131.
- 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.
- Haymond MW. Hypoglycemia in infants and children. Endocrinol Metab Clin North Am 1989; 18:211.
- Verrotti A, Fusilli P, Pallotta R, et al. Hypoglycemia in childhood: a clinical approach. J Pediatr Endocrinol Metab 1998; 11 Suppl 1:147.
- 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.
- Roe TF, Kogut MD. Hypopituitarism and ketotic hypoglycemia. Am J Dis Child 1971; 121:296.
- 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.
- 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.
- 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.
- Cornblath M, Pildes RS, Schwartz R. Hypoglycemia in infancy and childhood. J Pediatr 1973; 83:692.
- van Hasselt PM, Ferdinandusse S, Monroe GR, et al. Monocarboxylate transporter 1 deficiency and ketone utilization. N Engl J Med 2014; 371:1900.
- GLUCOSE HOMEOSTASIS IN NORMAL INFANTS AND CHILDREN
- DEFINITION OF HYPOGLYCEMIA
- ETIOLOGY OF HYPOGLYCEMIA
- CLINICAL FEATURES
- Children and adults
- - Autonomic symptoms
- - Neuroglycopenic symptoms
- IMMEDIATE MANAGEMENT
- Critical samples
- - Blood
- - Urine
- - Glucose therapy
- Oral therapy
- Intravenous therapy
- - Glucagon
- - Monitoring
- EVALUATION FOR THE CAUSE OF HYPOGLYCEMIA
- - Age at onset
- - Triggers
- - Past medical history
- - Family history
- Physical examination
- Laboratory testing
- Subsequent testing for unexplained hypoglycemia
- - Elective fast
- - Glucagon stimulation test
- - Interpretation of results
- Fatty acid oxidation disorders
- Defects in gluconeogenesis or glycogen metabolism
- Additional testing
- SUMMARY AND RECOMMENDATIONS
- Clinical presentation and diagnosis
- Evaluation for the cause