AIMS:To define clinical, metabolic, and hormonal characteristics of preterm infants relative to glucagon responsiveness. METHODS:Two phase study of 78 preterm infants (25-36 weeks gestation) on regular four hourly feeds anticipating discharge home at 36 weeks mean corrected gestation. In phase 1 infants were fasted until hypoglycaemic, or maximally for eight hours. Endocrine and metabolic profiles were obtained at completion. Phase 2 was performed the following day. A feed was omitted and replaced by a bolus dose of intravenous glucagon (100 micro g/kg). Main outcome measures were measurements of blood glucose and lactate concentrations, taken immediately pre-glucagon, and thereafter every 15 minutes for 60 minutes. A rise in glucose concentration of >1 mmol/l (55 infants) was defined as an adequate response to glucagon. An inadequate glycaemic response was <1 mmol/l (23 infants). RESULTS:Several differences in fasting blood glucose and hormone concentrations were identified in infants with an inadequate glycaemic response to glucagon compared to those with an adequate response: relative fasting hyperglycaemia (mean 3.7 v 3.3 mmol/l, p = 0.008); fasting hyperinsulinaemia (mean 4.3 v 2.6 mU/l, p = 0.014); an increased insulin:glucagon ratio (0.19 v 0.11, p = 0.014), and a lower insulin sensitivity QUICKI index (0.19 v 0.22, p = 0.04). There was no distinctive phenotype to reliably predict response to glucagon. CONCLUSION:Some preterm infants show an inadequate glycaemic response to glucagon and have features suggestive of insulin resistance. The potential long term implications of such insulin resistance may have appreciable public health consequences.

BACKGROUNDDevelopmental failures to adequately control postnatal blood glucose levels are common in the transition from fetal to infant life and can persist for many months. The standard method of functionally measuring hepatic glucose production and/or disordered glucose production is the response to a glucagon tolerance test.METHODWe adapted the standard glucagon tolerance test used for children and adults for use in preterm infants. 79 consecutive preterm infants gestational age range 25-36 weeks (mean 32.2 weeks), mean birth weight 1.66 kg admitted to the Neonatal Intensive Care Unit, Ninewells Hospital, Dundee and who survived to discharge home were recruited into the study. At the time of discharge home the characteristics of the group were as follows: adjusted mean gestational age 36.7 weeks, mean discharge weight 2.23 kg.RESULTSIn this study of preterm infants the maximal increase in plasma glucose following administration of a glucagon tolerance test is 1.39 +/- 07 mmol/L, n = 78 (range 0-3.98 mmol/L).CONCLUSIONSAn increase in plasma glucose of less than 4 mmol/L is considered abnormal in adults following administration of a fasting glucagon tolerance test. The responses of preterm infants and adults to glucagon are clearly different. The attenuated response to glucagon in the preterm infants is consistent with the low levels of hepatic glucose-6-phosphatase activity in premature infants as glucose-6-phosphatase is the terminal step of the two main pathways of liver glucose production.

Conference Abstract| July 01 2002 Glucagon Stimulation in Pre-Term Infants: Markers of Insulin Resistance Predict Response L. Jackson; L. Jackson Search for other works by this author on: This Site PubMed Google Scholar A. McGeechan; A. McGeechan Search for other works by this author on: This Site PubMed Google Scholar A. Burchell; A. Burchell Search for other works by this author on: This Site PubMed Google Scholar R. Hume R. Hume Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (2002) 103 (s47): 19P. https://doi.org/10.1042/cs103019P Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation L. Jackson, A. McGeechan, A. Burchell, R. Hume; Glucagon Stimulation in Pre-Term Infants: Markers of Insulin Resistance Predict Response. Clin Sci (Lond) 1 July 2002; 103 (s47): 19P. doi: https://doi.org/10.1042/cs103019P Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu nav search search input Search input auto suggest search filter All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 2002 The Biochemical Society and the Medical Research Society2002 Article PDF first page preview Close Modal You do not currently have access to this content.

BACKGROUND:Hepatic glucose-6-phosphatase activity is low at birth, and in term infants rises rapidly to adult levels. In contrast, in most preterm infants, it remains low postnatally making them vulnerable to repeated hypoglycaemic episodes, resultant cerebral damage, or risk of sudden and unexpected death.AIMS:To investigate the clinical features of preterm infants with low glucose-6-phosphatase enzyme activity to determine the influencing factors.METHODS:Clinical data from 36 preterm infants were correlated by stepwise multiple regression analysis with V(max) of hepatic glucose-6-phosphatase as the dependent variable.RESULTS:The most significant correlation was with the administration of insulin (units/kg/h postnatal life) with lesser effects of respiratory distress syndrome and dopamine administration. The V(max) changes reflected changes in the level of expression of the glucose-6-phosphatase protein.CONCLUSION:In a variety of animal models, hepatic glucose-6-phosphatase levels have been shown to decrease in response to insulin, which also decreases transcription of the glucose-6-phosphatase gene. The association of insulin administration with high levels of hepatic glucose-6-phosphatase activity and protein expression was therefore most unexpected. Results from model systems, or adults, must be extrapolated to the metabolism of preterm infants with caution.

In a series of 79 consecutive preterm infants who were ready for discharge, 14 (18%) infants were unable to maintain normal concentrations of blood glucose. This finding suggests that a significant number of preterm infants are at risk of hypoglycemia at home if a feed is omitted or delayed.