medwireNews: A report of empirical sulphonylurea therapy in neonatal diabetes prior to genetic diagnosis highlights contrasting approaches to the problem.

The study details nine infants who were diagnosed with diabetes within 14 days of birth and were subsequently trialled on sulphonylurea medication while awaiting the results of genetic testing. For these cases, which were recorded in the University of Chicago Monogenic Diabetes Registry, the time between the onset of diabetes and genetic diagnosis ranged from 28 to 252 days.

In the meantime, eight of the infants were successfully transitioned from insulin to sulphonylurea therapy, report study author Siri Atma Greeley (The University of Chicago, Illinois, USA) and colleagues in The Journal of Clinical Endocrinology & Metabolism.

The registry as a whole contained data on 154 infants, of whom 47% had confirmed potassium channel mutations. Therefore, empirical sulphonylurea therapy should be successful about half of the time, “and would provide great relief to families facing the prospect of taking home a baby with diabetes, especially for those who may have limited education, resources and support”, says the team.

Commenting on the paper for medwireNews, Andrew Hattersley, Professor of Molecular Medicine at the University of Exeter Medical School in the UK, agreed that it is critical to give the correct treatment as soon as possible. The alternative to empirical treatment, he said, “is to say we shouldn’t tolerate any delay,” because genetic diagnosis “makes a dramatic difference to the therapy.”

He said: “If ever there was a case for a rapid genetic test, done as soon as the sample is received, this is it.”

Hattersley noted that the 2014 International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines call for immediate genetic testing. To remove barriers to rapid testing, Hattersley’s team has Wellcome Trust funding to provide free genetic testing for neonatal diabetes; they accept samples from across the world, with results available within 1 week.

Indeed, in their report, Greeley et al note their findings may be “most applicable to the US, where barriers remain to obtaining genetic testing with appropriate cost reimbursement.” The “inordinate delay” seen for many cases in their study supports trying empirical therapy at diagnosis, they say.

The infants had variable responses to sulphonylurea therapy. Insulin was discontinued within a day in two patients, whereas one required insulin injections for a further 14 days. One patient continued to need insulin even when taking glyburide up to 1.0 mg/kg per day, and C-peptide was undetectable, indicating no endogenous insulin secretion, so the sulphonylurea was discontinued. Genetic testing failed to find a cause of diabetes in this patient, whereas five neonates had potassium channel mutations and three had transient neonatal diabetes.

“I don’t think it’s harmful to give sulphonylureas to people who actually need insulin therapy”, said Hattersley, “but it’s not helpful and it’s not the right treatment.”

He estimates that their laboratory receives samples from 50–60% of worldwide neonatal diabetes cases for genetic testing. “I do think because genetics has become so definitive and has transformed everything, it almost seems like a retrospective step to go trying a therapy.”

By Eleanor McDermid, Senior medwireNews Reporter

J Clin Endocrinol Metab 2014; Advance online publication

Free abstract