Neonatal diabetes mellitus: from understudy to center stage

Although neonatal diabetes mellitus is rare, its molecular basis has far-reaching implications for understanding the regulation of beta cell function, a prerequisite for understanding and treating type1 and type 2 diabetes mellitus especially by the manipulation of stem cells. The purpose of this review is to highlight the recent exciting discoveries concerning the genetic and molecular basis of the spectrum of disorders constituting neonatal diabetes mellitus.

Recent reports in the literature, all in the past year, have identified activating mutations in the KATP channel that prevent its closure and hence insulin secretion as the major cause of permanent neonatal diabetes mellitus. Concurrently, a transgenic mouse model of transient neonatal diabetes mellitus due to mutations in ZAC/HYMAI provides an exquisite tool to study its human counterpart. Already, mutations in KATP and ZAC/HYMAI have been shown to be associated with type 1 and type 2 diabetes mellitus in later life; some mutations in KATP are amenable to treatment with sulfonylureas.

The discoveries of the genes responsible for rarely occurring transient and permanent neonatal diabetes mellitus, and transgenic animal models to study them, are exciting milestones on the road to understanding and treating the common forms of type 1 and type 2 diabetes mellitus in children and adolescents.