Sulfonylurea Treatment Before Genetic Testing in Neonatal Diabetes: Pros and Cons

Abstract

Sulfonylurea therapy appears to be safe and often successful in neonatal diabetes patients before genetic testing results are available; however, larger numbers of cases must be studied. Given the potential beneficial effect on neurodevelopmental outcome, glycemic control, and the current barriers to expeditious acquisition of genetic testing, an empiric inpatient trial of sulfonylurea can be considered. However, obtaining a genetic diagnosis remains imperative to inform long-term management and prognosis.

Sulfonylurea in the treatment of neonatal diabetes mellitus children with heterogeneous genetic backgrounds

“…It is also apparent from several studies that glycemic control is dissatisfactory in NDM patients on insulin momotherapy (14). Furthermore, early SU treatment can improve glycemic control and ameliorate neurodevelopmental disability among neonatal patients with KCNJ11 mutations that are commonly found in patients with NDM (14)(15)(16)(17). With these pieces of evidence, the high efficiency of SU therapy shown in our study suggested that SU can be considered as a first-line treatment for patients with NDM.…”

“…It was generally recommended that SU treatment should be initiated for a patient with NDM once his/her genetics were confirmed to be associated with the overactivation of the K ATP channel (22) despite it being challenged by the inefficiency of genetic diagnosis that may deprive the neonates of benefits gained by the early introduction of SU (15)(16)(17)23). In our study the success of SU monotherapy in 94% (15/16) patients with NDM without noticeable side effects suggested that SU can be an efficient treatment in NDM patients.…”

“…These barriers include the high cost of genetic tests as well as the lack of physicians' knowledge of genetic testing and consulting. It was shown that among patients with NDM, the median time delay of genetic diagnosis was more than 10 weeks after the clinical diagnosis, while sulfonylurea therapies were safe and often successful in patients with NDM before genetic testing results are available (17). Meanwhile, owing to the irregular feeding habits of newborns and infants, it is a great challenge for pediatricians and parents to establish an effective long-term insulin therapy to patients with NDM (1,13).…”

“…It was known that the establishment of an effective long-term insulin therapy to patients with NDM is a great challenge for pediatricians and parents due to irregular feeding habits of newborns and infants (1,13). Meanwhile, early SU treatment was capable of improving glycemic control and ameliorating neurodevelopmental disability among patients with NDM (14)(15)(16)(17). These pieces of evidence together suggested that SU monotherapy can be applied to patients with NDM in general, especially in developing regions where effective genetic diagnosing is yet to be established.…”

Continued lessons from theINSgene: an intronic mutation causing diabetes through a novel mechanism

“…The underlying genetic cause remains unknown in 20–30% of neonatal diabetes cases,6 7 and the University of Chicago Monogenic Diabetes Registry was established to identify novel aetiological genetic mechanisms in families with suspected monogenic diabetes, in addition to following families with known forms of monogenic diabetes. Here we outline the identification of a deep intronic INS mutation causing diabetes through a novel mechanism.…”