Monogenic Disorders of the β‐Cell

Abstract

Defects in pancreatic β‐cell glucose–insulin secretion coupling can cause undersecretion of insulin and hence hyperglycemia and diabetes, or more rarely oversecretion of insulin and hypoglycemia. The most common cause of β‐cell dysfunction is seen in type 2 diabetes but this is polygenic and still imprecisely defined. Monogenic disorders of the β‐cell account for 3–4% of diabetes and so they are an important cause of diabetes in their own right. The recognition of a monogenic etiology of diabetes has clinical management implications determining clinical course, nonpancreatic manifestations, and choice of treatment. In addition to this clinical importance, the discovery and study of monogenic disorders has given further insight into the physiology and pathophysiology of the β‐cell. This chapter will focus on the most prevalent of the monogenic disorders of the β‐cell: maturity‐onset diabetes of the young and mitochondrial inherited diabetes and deafness. We will also discuss hyperinsulinemia, Wolfram syndrome, thiamine responsive megaloblastic anemia syndrome, Wolcott–Rallison syndrome, mutant insulins, and familial hyperproinsulinemia.