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

Objective: The pathogenic base of neonatal diabetes mellitus (NDM) is highly heterogeneous. Sulfonylurea (SU) has been successfully applied in majority of NDM patients with K-ATP channel mutations; however, its rationality and effectiveness among patients with NDM stemmed from other genetic mutations have not been established. The objective of the present study was to investigate the effectiveness of SU therapy in NDM patients with heterogeneous genetic backgrounds. Methods: We identified 16 patients with NDM. These patients underwent SU titration and were followed after successful SU monotherapy. All patients were sequenced for all exons and adjacent intron-exon junctions of ABCC8, KCNJ11, and INS, and analyzed for 6q24 methylation defects. SU regimens were applied and glycemic status was evaluated in each patient. Results: Of the 16 patients, 15 (94%) reached glycemic goal (7-10 mmol/L) after SU monotherapy except one patient with the INS mutation. No significant side effects or organ damage were found in any of the 16 patients. Among these patients, five were found to harbor ABCC8 mutations, another five had mutations in KCNJ11, two had INS gene mutations, one with 6q24 hypomethylation, and three were absent for defects in genes tested. Conclusion: Our study showed that SU monotherapy resulted in satisfactory glycemic control in most of the patients with NDM whose genetic defects are heterogeneous. The usage of SU may be considered as first-line therapy for patients with NDM in developing countries where effective genetic screening is not established.