Insights into the Genetics and Signaling Pathways in Maturity-Onset Diabetes of the Young

Abstract

Diabetes Mellitus (DM) is a complex disease with a significant impact in today’s world. Studies have emphasized the crucial role of genetics in DM, unraveling the distinction of monogenic diabetes from the most common types that have been recognized over the years, such as type 1 diabetes (T1DM) and type 2 diabetes (T2DM). A literature search was carried out to scrutinize the subtypes of maturity-onset diabetes of the young (MODY), as well as the connection between the recognized genetic and molecular mechanisms responsible for such phenotypes. Thus far, 14 subtypes of MODY have been identified. Here, the authors review the pathophysiological and molecular pathways in which monogenic diabetes genes are involved. Despite being estimated to affect approximately 2% of all T2DM patients in Europe, the exact prevalence of MODY is still unknown, enhancing the need for research focused on biomarkers. Due to its impact in personalized medicine, a follow-up of associated complications, and genetic implications for siblings and offspring of affected individuals, it is imperative to diagnose the monogenic forms of DM accurately. Currently, advances in the genetics field has allowed for the recognition of new DM subtypes, which until now were considered to be slight variations of the typical forms. New molecular insights can define therapeutic strategies, aiming for the prevention, correction, or at least delay of β-cell dysfunction. Thus, it is imperative to act in the close interaction between genetics and clinical manifestations to improve diagnosis and individualize treatment.

Evaluation of Bayesian Linear Regression Models for Gene Set Prioritization in Complex Diseases

“…Furthermore, the identification of the “ Maturity onset diabetes of the young ” (MODY) pathway adds another layer of complexity to our understanding of T2D. MODY represents a specific monogenic form of diabetes, accounting for approximately 2% of European individuals with T2D (57). While traditionally considered distinct entities, recent studies have shed light on potential connections between MODY and T2D pathogenesis.…”

Evaluation of Bayesian Linear Regression Derived Gene Set Test Methods

“…In the case of T2D, the "Maturity onset diabetes of the young" (MODY) pathway showed a particularly significant association. MODY, a distinctive monogenic type of diabetes, constitutes roughly 2% of individuals of European descent diagnosed with T2D (Sousa et al, 2022). Although historically viewed as separate conditions, recent research has hinted at possible links between MODY and the development of T2D.…”

New Advances in Diabetes Genetics

“…The molecular diagnosis is fundamental in rare forms to choose the appropriate treatment, to reduce the risk of consequences, and for genetic counselling. This Special Issue contains two reviews [ 1 , 2 ], three original papers [ 3 , 4 , 5 ], and one case report [ 6 ] that address genetic issues in diabetes mellitus.…”

“…Sousa et al [ 2 ] review the genetics and signalling pathways of MODY. Their paper covers the mechanisms underlying hyperglycaemia and provides comprehensive and interesting insights for the readers.…”

“…Their paper covers the mechanisms underlying hyperglycaemia and provides comprehensive and interesting insights for the readers. This rare form of diabetes is an interesting model for personalized medicine [ 2 , 7 ].…”