Abstract
The relation between hepatic glucose production rate (HGPR) and plasma concentrations of insulin and glucagon was investigated in four term neonates who had severe hypoglycaemia. The hepatic glucose production rate was less than 20% of normal for fasting term neonates in all four babies and yet insulin concentrations were never greater than 12 microU/ml; two babies had very low glucagon concentrations (less than 60 ng/l). Two further neonates with similar histories also had plasma glucagon concentrations that were also extremely low (less than 20 ng/l). A single intravenous bolus of glucagon caused a rapid rise in hepatic glucose production rate towards the normal range, which was sustained for many hours after the bolus had been given. Diazoxide given to one baby suppressed previously 'normal' insulin concentrations still further (4.2 to less than 1.6 microU/ml) and thereby restored the hepatic glucose production rate to normal. In view of the normal plasma insulin concentrations at a time when the hepatic glucose production rate was reduced, we feel that the absolute concentration of insulin may be less important than the insulin/glucagon molar ratio in the control of glucose homeostasis in this group of infants. The changing of this ratio by means of boluses of glucagon may be useful in preventing rebound hypoglycaemia, which so often occurs when dextrose infusions are reduced either accidentally or in an attempt to restart oral feeds.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bier D. M., Leake R. D., Haymond M. W., Arnold K. J., Gruenke L. D., Sperling M. A., Kipnis D. M. Measurement of "true" glucose production rates in infancy and childhood with 6,6-dideuteroglucose. Diabetes. 1977 Nov;26(11):1016–1023. doi: 10.2337/diab.26.11.1016. [DOI] [PubMed] [Google Scholar]
- Cohen M. S., Bower R. H., Fidler S. M., Johnsonbaugh R. E., Sode J. Inhibition of insulin release by diphenylhydantoin and diazoxide in a patient with benign insulinoma. Lancet. 1973 Jan 6;1(7793):40–41. doi: 10.1016/s0140-6736(73)91251-8. [DOI] [PubMed] [Google Scholar]
- Collins J. E., Leonard J. V. Hyperinsulinism in asphyxiated and small-for-dates infants with hypoglycaemia. Lancet. 1984 Aug 11;2(8398):311–313. doi: 10.1016/s0140-6736(84)92685-0. [DOI] [PubMed] [Google Scholar]
- Cowett R. M., Oh W., Schwartz R. Persistent glucose production during glucose infusion in the neonate. J Clin Invest. 1983 Mar;71(3):467–475. doi: 10.1172/JCI110791. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Girard J. R., Caquet D., Bal D., Guillet I. Control of rat liver phosphorylase, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities by insulin and glucagon during the perinatal period. Enzyme. 1973;15(1):272–285. [PubMed] [Google Scholar]
- Haymond M. W., Karl I. E., Pagliara A. S. Increased gluconeogenic substrates in the small-for-gestational-age infant. N Engl J Med. 1974 Aug 15;291(7):322–328. doi: 10.1056/NEJM197408152910702. [DOI] [PubMed] [Google Scholar]
- Kalhan S. C., Savin S. M., Adam P. A. Attenuated glucose production rate in newborn infants of insulin-dependent diabetic mothers. N Engl J Med. 1977 Feb 17;296(7):375–376. doi: 10.1056/NEJM197702172960706. [DOI] [PubMed] [Google Scholar]
- Ktorza A., Girard J. R., Kinebanyan M. F., Picon L. Hyperglycaemia induced by glucose infusion in the unrestrained pregnant rat during the last three days of gestation: metabolic and hormonal changes in the mother and the fetuses. Diabetologia. 1981 Dec;21(6):569–574. doi: 10.1007/BF00281551. [DOI] [PubMed] [Google Scholar]
- Malherbe C., Burrill K. C., Levin S. R., Karam J. H., Forsham P. H. Effect of diphenylhydantoin on insulin secretion in man. N Engl J Med. 1972 Feb 17;286(7):339–342. doi: 10.1056/NEJM197202172860702. [DOI] [PubMed] [Google Scholar]
- Midgley A. R., Jr, Rebar R. W., Niswender G. D. Radioimmunoassays employing double antibody techniques. Acta Endocrinol Suppl (Copenh) 1969;142:247–254. doi: 10.1530/acta.0.062s247. [DOI] [PubMed] [Google Scholar]
- Milner R. D., Wright A. D. Plasma glucose, non-esterified fatty acid, insulin and growth hormone response to glucagon in the newborn. Clin Sci. 1967 Apr;32(2):249–255. [PubMed] [Google Scholar]
- Ogata E. S. Carbohydrate metabolism in the fetus and neonate and altered neonatal glucoregulation. Pediatr Clin North Am. 1986 Feb;33(1):25–45. doi: 10.1016/s0031-3955(16)34968-9. [DOI] [PubMed] [Google Scholar]
- STEELE R. Influences of glucose loading and of injected insulin on hepatic glucose output. Ann N Y Acad Sci. 1959 Sep 25;82:420–430. doi: 10.1111/j.1749-6632.1959.tb44923.x. [DOI] [PubMed] [Google Scholar]
- Stanley C. A., Baker L. Hyperinsulinism in infancy: diagnosis by demonstration of abnormal response to fasting hypoglycemia. Pediatrics. 1976 May;57(5):702–711. [PubMed] [Google Scholar]
- Vidnes J., Oyasaeter S. Glucagon deficiency causing severe neonatal hypoglycemia in a patient with normal insulin secretion. Pediatr Res. 1977 Sep;11(9 Pt 1):943–949. doi: 10.1203/00006450-197709000-00001. [DOI] [PubMed] [Google Scholar]
- White E., Welch V. M., Sun T., Sniegoski L. T., Schaffer R., Hertz H. S., Cohen A. The accurate determination of serum glucose by isotope dilution mass spectrometry--two methods. Biomed Mass Spectrom. 1982 Sep;9(9):395–405. doi: 10.1002/bms.1200090907. [DOI] [PubMed] [Google Scholar]
- Wootton R., Ashley K. ITA, a portable program for the interactive analysis of data from tracer experiments. Comput Biol Med. 1985;15(5):247–257. doi: 10.1016/0010-4825(85)90008-3. [DOI] [PubMed] [Google Scholar]
- Wootton R., Ford G. C., Cheng K. N., Halliday D. Calculation of turnover rates in stable-isotope studies. Phys Med Biol. 1985 Oct;30(10):1143–1149. doi: 10.1088/0031-9155/30/10/013. [DOI] [PubMed] [Google Scholar]