How do I diagnose Maturity Onset Diabetes of the Young in my patients?

Abstract

Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes diagnosed in young individuals that lack the typical features of type 1 and type 2 diabetes. The genetic subtype of MODY determines the most effective treatment and this is the driver for MODY genetic testing in diabetes populations. Despite the obvious clinical and health economic benefits, MODY is significantly underdiagnosed with the majority of patients being inappropriately managed as having type 1 or type 2 diabetes. Low detection rates result from the difficulty in identifying patients with a likely diagnosis of MODY from the high background population of young onset type 1 and type 2 diabetes, compounded by the lack of MODY awareness and education in diabetes care physicians. MODY diagnosis can be improved through (1) access to education and training, (2) the use of sensitive and specific selection criteria based on accurate prediction models and biomarkers to identify patients for testing, (3) the development and mainstream implementation of simple criteria-based selection pathways applicable across a range of healthcare settings and ethnicities to select the most appropriate patients for genetic testing and (4) the correct use of next generation sequencing technology to provide accurate and comprehensive testing of all known MODY and monogenic diabetes genes. The creation and public sharing of educational materials, clinical and scientific best practice guidelines and genetic variants will help identify the missing patients so they can benefit from the more effective clinical care that a genetic diagnosis brings.

Keywords: Maturity Onset Diabetes of the Young; biomarkers; delivery of health care; genetic testing; next-generation sequencing; patient selection; precision medicine.

Figure 1

A strategy for identifying patients to refer for MODY testing. This strategy is based on the eligibility criteria for NHS funded MODY testing in England, available at https://www.diabetesgenes.org/tests‐for‐diabetes‐subtypes/guidelines‐for‐genetic‐testing‐in‐mody/ and within NHSE's Rare and inherited disease eligibility criteria document— https://www.england.nhs.uk/wp‐content/uploads/2018/08/Rare‐and‐inherited‐disease‐eligibility‐criteria‐2021‐22‐v2.pdf. These criteria were created using unpublished clinical information, family history and genetic testing data from the UK MODY registry at the Exeter Genomics Laboratory with the aim to achieve a MODY diagnosis in roughly one in every four patients referred for testing. BMI, body mass index; MODY, Maturity Onset Diabetes of the Young; NGS, next generation sequencing; PRS, polygenic risk score; WGS, whole genome sequencing. [Color figure can be viewed at wileyonlinelibrary.com]