Monogenic diabetes mellitus and clinical implications of genetic diagnosis

Abstract

Monogenic diabetes mellitus, which is diabetes caused by a defect in a single gene that is associated with β cell function or insulin action, accounts for 1% to 6% of all pediatric diabetes cases. Accurate diagnosis is important, as the effective treatment differs according to genetic etiology in some types of monogenic diabetes: high-dose sulfonylurea treatment in neonatal diabetes caused by activating mutations in KCNJ11 or ABCC8; low-dose sulfonylurea treatment in HNF1A/HNF4A-diabetes; and no treatment in GCK diabetes. Monogenic diabetes should be suspected by clinicians for certain combinations of clinical features and laboratory results, and approximately 80% of monogenic diabetes cases are misdiagnosed as type 1 diabetes or type 2 diabetes. Here, we outline the types of monogenic diabetes and the clinical implications of genetic diagnosis.