Breakthroughs in monogenic diabetes genetics: from pediatric forms to young adulthood diabetes

Abstract

Several monogenic forms of pancreatic beta-cell dysfunction leading to non-autoimmune diabetes have been diagnosed early in life, in neonates or during infancy, in childhood or even in young adulthood, with genetically heterogeneous aetiologies.They include neonatal diabetes mellitus, non auto-immune diabetes in infancy and childhood, dominantly inherited young-onset diabetes and very rare diabetes-associated syndromes. More than ten genes that are highly expressed in the pancreatic beta-cell have been identified in these monogenic subtypes of diabetes, and several aetiological mechanisms of beta-cell dysfunction are involved including reduced beta-cell number, failure of glucose sensing and increased destruction of the beta-cell, which result in inadequate insulin secretion despite a chronic hyperglycemia. There is rising evidence that common polymorphisms in the genes implicated in monogenic diabetes may also be involved in susceptibility to adulthood type 2 diabetes. This review describes the major advances arising from the identification of the genetic and molecular mechanisms underlying the clinical features of various conditions of diabetes in the young, and how these new genetic and biological insights led to novel pharmacogenomic approaches.