Clinical Manifestations and Biomarkers of the Maturity-Onset Diabetes of the Young

Maturity-onset diabetes of the young is the most common monogenic diabetes form affecting between 1% and 5% of all diabetes cases. Clinical characteristics include young onset (usually before 45 years), autosomal dominant inheritance, absence of autoantibodies and metabolic syndrome, and impaired glucose-dependent insulin secretion. To date, at least 14 maturity-onset diabetes of the young subtypes have been identified, harboring numerous mutations that contribute to highly heterogeneous clinical phenotypes. While much is known about the common subtypes of maturityonset diabetes of the young linked to mutations in HNF4A, GCK, HNF1A, and HNF1B; little is known about relatively rare mutations in IPF1/PDX1, NEUROD1, KLF11, PAX4, INS, BLK, ABCC8, KCNJ11, and APPL1 genes. However, with the advent of next-generation sequencing, rare maturity-onset diabetes of the young subtypes are being increasingly reported worldwide. Although nearly 6 decades have passed since the first cases were identified, maturity-onset diabetes of the young is often misdiagnosed as type 1 or type 2 diabetes mellitus due to overlapping clinical features, limited use of genetic testing, and lack of awareness of this type of diabetes. Although there are many clinical characteristics suggesting the diagnosis of maturity-onset diabetes of the young, there is no single criterion. Identifying clinical features of different maturity-onset diabetes of the young subtypes can reduce the number and cost of genetic testing; On the other hand, early diagnosis will reduce the risks of inappropriate treatment and related side effects. The aim of this review is to highlight the role of clinical features, demonstrate the effectiveness of clinical biomarkers in the differential diagnosis of maturity-onset diabetes of the young subtypes, and identify the most suitable candidates for genetic testing.

Cite this article as: Satman I. Clinical manifestations and biomarkers of the maturity-onset diabetes of the young. Endocrinol Res Pract. 2023;27(2):98-112.