Research finds genetic mutations responsible for neonatal diabetes in premature infants

Researchers from the University of Exeter Medical School have identified genetic predispositions for the development of neonatal diabetes in premature newborns.
The study findings, published in the journal Pediatrics, show evidence of different genetic causes of neonatal diabetes, which could be picked up by genetic testing in premature infants.
Because hyperglycemia is a common complication of prematurity, neonatal diabetes is considered a rare cause of hyperglycemia, hence few studies have investigated patients with permanent neonatal diabetes who were born prematurely.
Dr Andrew T. Hattersley and his colleagues decided to address this issue by assessing through genetic testing the clinical characteristics of 750 patients with neonatal diabetes.
The results revealed a common genetic cause of neonatal diabetes in 79.7 per cent (598) of infants, of whom 16 per cent were born preterm.
However, fewer preterm babies had defined genetic patterns for their diabetes compared with those born at 37 weeks or after.
The researchers noticed the presence of defects in what is known as DNA methylations (at chromosome 6q24), which play an important role for gene regulation in development and disease.
The scientists also observed GATA6 mutations, found in previous studies to cause a wide spectrum of diabetes manifestations, ranging from impaired formation of the pancreas to adult-onset diabetes.
Abnormal DNA methylations were significantly more common in preterm (27 per cent) than term (12 per cent) infants. Similarly, GATA6 mutations were more prevalent in premature infants (9 per cent) than those born at term (2 per cent).
The researchers also looked for other DNA mutations typical of neonatal diabetes, such as KCNJ11 and ABCC8, which can both influence insulin secretion regulation in profound ways.
By contrast with the methylation defects mentioned earlier, mutations in KCNJ11 were significantly less common in preterm infants (21 vs 34 per cent). And there was no clinically significant difference in ABCC8 mutations either.
However, 37 per cent of preterm infants had adenosine triphosphate-sensitive potassium (KATP) channel mutations, which are associated with KCNJ11 and ABCC8. Previous genetic studies have shown that overactivation of the KATP channel causes severe undersecretion of insulin.
Researchers suggest that spotting early on a genetic predisposition to overactivation of KATP is important as patients can be transferred to a diabetes medication like sulphonylureas to increase insulin release and therefore improve glycemic control.
Overall, only 13 out of 750 preterm infants had a genetic cause identified, but in light of certain of the findings, the authors recommend genetic referral of preterm patients with persistent hyperglycemia until a gestational age of 32 weeks.