CHARACTERIZATION OF THE MODY3 PHENOTYPE - EARLY-ONSET DIABETES CAUSEDBY AN INSULIN-SECRETION DEFECT

Maturity-onset diabetes of the young (MODY) type 3 is a dominantly inh erited form of diabetes, which is often misdiagnosed as non-insulin-de pendent diabetes mellitus (NIDDM) or insulin-dependent diabetes mellit us (IDDM). Phenotypic analysis of members from four large Finnish MODY 3 kindreds (linked to chromosome 12q with a maximum lod score of 15) r evealed a severe impairment in insulin secretion, which was present al so in those normoglycemic family members who had inherited the MODY3 g ene. In contrast to patients with NIDDM, MODY3 patients did not show a ny features of the insulin resistance syndrome. They could be discrimi nated from patients with IDDM by lack of glutamic acid decarboxylase a ntibodies (GAD-Ab). Taken together with our recent findings of linkage between this region on chromosome 12 and an insulin-deficient form of NIDDM (NIDDM2), the data suggest that mutations at the MODY3/NIDDM2 g ene(s) result in a reduced insulin secretory response, that subsequent ly progresses to diabetes and underlines the importance of subphenotyp ic classification in studies of diabetes.