Abstract
Extract: The commonest clinical type of hypoglycemia in childhood presents as “ketotic hypoglycemia,” a syndrome which typically remits spontaneously before adolescence. In young children with the severe form of this syndrome, deficient catecholamine secretion and, recently, decreased mobilization of gluconeogenic substrate (alanine) have been shown. The present study concerns five children with ketotic hypoglycemia, aged 2.5 to 9.5 years, and six control children, of similar ages. Each received (7) an infusion of 2-deoxy-D-glucose (2-DG) to test the catecholamine response and (2) intravenous glucagon before and after a 26–28-hr fast, to define possible difference in the response of substrates and hormones, with particular reference to alanine. In the control group, the infusion of 2-DG, 50 mg/kg body wt over 30 min, induced anxiety, hunger or thirst and sweating, as well as a sustained rise in plasma glucose from 78 ± 5 (mean ± SEM) to 156 ± 13.5 mg/100 ml from 1—3 hr after beginning the infusion. There was a transient rise in renin activity in plasma (PRA) from 2.0 ± 0.5 to a peak of 5.8 ± 1.2 ng/ml/hr. By contrast, in the children with hypoglycemia, no clinical response was observed, and there was no change in either glucose in plasma, which remained at 77 ± 6 mg/100 ml, or in PRA (1.3 ± 0.3 to 1.0 ± 0.5 ng/ml/hr). After a period of unrestricted diet, and after an overnight fast, values of plasma glucose, insulin, glucagon, β-hydroxybutyrate, and alanine were the same in the two groups. In both groups intravenous glucagon, 30 μg/kg, was followed by a comparable rise in glucose in plasma and immunoreactive insulin and a comparable fall in alanine in plasma. During the subsequent fast, glucose and insulin in plasma declined similarly. Ketonuria appeared at the same time and β-hydroxybutyrate in plasma rose to equivalent values. The response to a second glucagon infusion was smaller after fasting both as to glucose in blood and plasma insulin, but once again similar for control and hypoglycemia groups. However, the fall in alanine in plasma was significantly greater in the hypoglycemic group during fasting (to 200 ± 13 μM for the control group compared with 151 ± 13 μM for the hypoglycemia group, P < 0.05) and at five time points (10, 30, 60, 90, and 120 min) after the second glucagon administration. Absence of hyperglycemic response to 2-DG in ketotic hypoglycemia suggests impaired catecholamine response. Further, after provocation by fasting and subsequent glucagon administration, the hypoalaninemia which resulted was more marked. Because epinephrine has been shown to raise alanine levels in plasma in man, it is hypothesized that a connection may exist between defective catechol secretion and alanine mobilization in ketotic hypoglycemia.
Speculation: Decreased availability of alanine in so-called ketotic hypoglycemia probably represents a defective metabolic system by which neoglucogenic substrates are not readily mobilized, rather than an absolute absence of substrate. One of the possible defective metabolic systems might be through the epinephrine secretion. However, the mobilizable pool of one of these neoglucogenic factors such as alanine could be small in the infants, and become bigger as muscle, which is a storage compartment of alanine, develops with age and puberty. If such is the case, it could be an explanation of the decrease of the frequency of attacks with age, generally at puberty.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sizonenko, P., Paunier, L., Vallotton, M. et al. Response to 2-Deoxy-D-glucose and to Glucagon in “Ketotic Hypoglycemia” of Childhood: Evidence for Epinephrine Deficiency and Altered Alanine Availability. Pediatr Res 7, 983–993 (1973). https://doi.org/10.1203/00006450-197312000-00007
Issue Date:
DOI: https://doi.org/10.1203/00006450-197312000-00007
Keywords
This article is cited by
-
Sympatho-adrenal response to hypoglycaemia in infants
European Journal of Pediatrics (1988)
-
Isolated glucocorticoid deficiency: metabolic and endocrine studies in a 5-year-old boy
European Journal of Pediatrics (1985)
-
Hypoglycemia in infancy and childhood
The Indian Journal of Pediatrics (1982)
-
Hypoketosis as a cause of symptoms in childhood hypoglycemia
European Journal of Pediatrics (1980)
-
Catecholamines and diabetes mellitus
Diabetologia (1979)