Physiological and clinical role of insulin in the neonate

Abstract

In the newborn infant, insulin secretion has to adjust in response to the switch from a regulated and continuous placental supply of glucose in utero to the delivery of intermittent oral feeds postnatally. Changes in insulin secretion must reflect its primary role for maintaining glucose homeostasis, but also its roles in promoting growth and anabolism and in the newborn disorders of insulin secretion or sensitivity, which present with hyperglycemia and impaired growth. Recent elucidation of the genetic basis of neonatal diabetes has helped to provide valuable insights into the molecular mechanisms of β-cell function and the potential for treatment of some patients with oral hypoglycemic agents, although the majority require prolonged subcutaneous insulin treatment, which may prove challenging. The recent development of insulin pump therapy has significantly improved the clinical management of these infants. Although they do not have neonatal diabetes, the preterm or very-low-birthweight infant, subjected to the combined effects of insulin resistance owing to the impact of intensive care, and relative insulin deficiency related to prematurity, may have long periods of hyperglycemia and impaired growth, which have been associated with adverse clinical outcomes. Although these infants often require insulin treatment, the optimal management of glucose control and use of insulin has not been determined and remains controversial.

Keywords::

• diabetes
• glucose
• hyperglycemia
• insulin
• neonate
• preterm

Acknowledgements

We are grateful to all the clinicians who were involved in the Neonatal Insulin Replacement Therapy Trial (NIRTURE) as well as those members of the research team based in the CTU in Cambridge. We would also like to thank all the staff who cared for the babies and the families who agreed to participate.

Financial & competing interests disclosure

David B Dunger and Kathryn Beardsall received an unrestricted research grant from Novo Nordisk for the Neonatal Insulin Replacement Therapy Trial (NIRTURE), and Medtronic provided the continuous glucose-monitoring system and sensors. Leeds General Infirmary research fund, Medtronic, the University of Cambridge, Department of Paediatrics, the NIHR Cambridge Biomedical Research Institute and NHS Research and Development also provided support. NIRTURE was adopted by the UK Medicines for Children Research Network. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.