Abnormal glucose homeostasis and fasting intolerance in patients with congenital porto-systemic shunts

Mirjam E van Albada; Pratik Shah; Terry G J Derks; Sabine Fuchs; Judith J M Jans; Valérie McLin; Hubert P J van der Doef

doi:10.3389/fendo.2023.1190473

Abnormal glucose homeostasis and fasting intolerance in patients with congenital porto-systemic shunts

Front Endocrinol (Lausanne). 2023 Aug 18:14:1190473. doi: 10.3389/fendo.2023.1190473. eCollection 2023.

Authors

Mirjam E van Albada¹, Pratik Shah², Terry G J Derks³, Sabine Fuchs⁴, Judith J M Jans⁵, Valérie McLin⁶, Hubert P J van der Doef⁷

Affiliations

¹ Department of Pediatric Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
² Department of Pediatric Endocrinology, The Royal London Childrens Hospital, Barts Health National Health Service (NHS) Trust and William Harvey Research Institute, Queen Mary University London, London, United Kingdom.
³ Department of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
⁴ Department of Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands.
⁵ Department of Genetics, Section Metabolic Diagnostics, University Medical Center Utrecht, Utrecht, Netherlands.
⁶ Swiss Pediatric Liver Center, Department of Pediatrics, Obstetrics, and Gynecology, University of Geneva, Geneva, Switzerland.
⁷ Department of Pediatric Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

Abstract

In physiological glucose homeostasis, the liver plays a crucial role in the extraction of glucose from the portal circulation and storage as glycogen to enable release through glycogenolysis upon fasting. In addition, insulin secreted by the pancreas is partly eliminated from the systemic circulation by hepatic first-pass. Therefore, patients with a congenital porto-systemic shunt present a unique combination of (a) postabsorptive hyperinsulinemic hypoglycaemia (HH) because of decreased insulin elimination and (b) fasting (ketotic) hypoglycaemia because of decreased glycogenolysis. Patients with porto-systemic shunts therefore provide important insight into the role of the portal circulation and hepatic function in different phases of glucose homeostasis.

Keywords: congenital hyperinsulinism; congenital porto-systemic shunt; glucose metabolism; hyperinsulinism; hypoglycaemia; insulin; portal circulation.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Fasting*
Glucose
Homeostasis
Humans
Hypoglycemia*
Insulin

Substances

Insulin
Glucose

Grants and funding

The International Registry of Congenital Porto-systemic Shunts (IRCPSS) is supported by ESPGHAN and EASL. The Meeting of Experts held in Geneva, Switzerland, in July 2022, where the idea of this paper was born, was supported by ESPGHAN, the EJP RD NSS, and SASL.