Monogenetic diabetes mellitus: precision diagnosis in clinical practice

Abstract

Introduction: Monogenic diabetes encompasses a spectrum of clinical disorders characterized by the onset of diabetes at early age, which include subtypes like neonatal diabetes, maturity onset diabetes of the young (MODY), and diverse syndromes associated with diabetes. MODY represents the predominant manifestation of monogenic diabetes, with estimated prevalence ranging from 0.5% to 5% among individuals diagnosed with non-autoimmune diabetes. However, MODY is currently underdiagnosed within the affected population due to lack of clinical recognition and to insufficient genetic testing. A correct molecular diagnosis is crucial for personalized treatment of these patients. Methods: The aim of this retrospective study was, to evaluate the diagnostic approach used in the diagnosis of monogenetic diabetes in an adult diabetes outpatient clinic. Furthermore, a comprehensive literature search was conducted for an updated overview of several subtypes of monogenic diabetes. Results: Genetic testing was performed in 105 adult patients (age: 37 (29-48)) and variants in diabetes-associated genes were identified in 35 patients (33%). GCK (49%), HNF1A (17%) and HNF1B (14%) accounted for most of the cases. Over the last decade genetic testing methods switched from single gene testing to multi-gene panel analysis and whole exome sequencing, with the potential to discover also rarer forms of monogenic diabetes. Conclusion: In the diagnosis of monogenic diabetes clinical assessment of detailed patients and family history, physical features, and biochemical measures, including C-peptide levels and type 1 diabetes antibodies is essential before referral for genetic testing. To provide the correct diagnosis for patients and their family retrospectively screening for presence of additional features and reevaluation of current diabetes form is recommended. The recognition of these subtypes will enhance the efficacy of the physician-based diagnostic approach for monogenic diabetes.

Date of Award	2023
Original language	English
Awarding Institution	Medical University Graz
Supervisor	Julia Mader (Supervisor)