# How hypoxia-induced diabetes develops and is maintained in children born preterm

## TL;DR

This paper explores how hypoxia in preterm infants may cause rapid-onset diabetes by affecting insulin and glucose transporter function.

## Contribution

The paper introduces a novel hypothesis linking hypoxia from breathing issues in preterm infants to diabetes development.

## Key findings

- Intermittent hypoxia may elevate cytosolic chloride in pancreatic beta-cells, impairing insulin secretion.
- Reduced WNK1 levels in skeletal muscle could disrupt GLUT4 function, affecting glucose transport.
- Prolonged sympathetic outflow from disrupted breathing may contribute to metabolic dysfunction.

## Abstract

A puzzling metabolic question is the emergence of rapid-onset diabetes in the postnatal period of pre-term infants without the usual preceding prodromal characteristics. The etio-pathophysiology is unclear, but continues to be a concern, since the prevalence remains a significant health issue. We hypothesize that this new diabetes type is hypoxemia-driven from compromised ventilation via periodic breathing or apnea of infancy during the immediate postnatal period. The resulting intermittent hypoxia leads to elevated cytosolic chloride levels in pancreatic beta-cells affecting insulin secretion and disturbed glucose transporter (GLUT) 4 function resulting from lowered With-no-lysine (k) kinase (WNK)1 levels in the skeletal musculature. In addition, the peripheral cellular effects are coupled with prolonged elevated sympathetic outflow elicited by the disrupted breathing. This mini-review discusses current research gaps and provides insights into potential interventions for the widespread epidemic of Type 1 and Type 2 diabetes.