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Chan et al. J Transl Genet Genom 2024;8:13-34 https://dx.doi.org/10.20517/jtgg.2023.36 Page 115

Chan et al. J Transl Genet Genom 2024;8:13-34 Journal of Translational
DOI: 10.20517/jtgg.2023.36
Genetics and Genomics

Perspective Open Access

Multifaceted nature of young-onset diabetes - can
genomic medicine improve the precision of

diagnosis and management?

1,2
1
Juliana C. N. Chan 1,2,3 , Elaine Chow 1,2,3,4 , Alice Kong 1,2,3 , Elaine Cheung , Tony O , Cadmon Lim 1,2,3 ,
1,3
1,3
1,3
1,3
Baoqi Fan , Sandra Tsoi , Yingnan Fan , Mai Shi , Risa Ozaki 1,2,3 , Ronald Ma 1,2,3 , Andrea Luk 1,2,3,4
1
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
2
Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong,
China.
3
Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
4
Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
Correspondence to: Prof. Juliana C. N. Chan, Department of Medicine and Therapeutics, The Chinese University of Hong Kong,
Prince of Wales Hospital, Shatin, New Territories, Hong Kong, China. E-mail: jchan@cuhk.edu.hk
How to cite this article: Chan JCN, Chow E, Kong A, Cheung E, O T, Lim C, Fan B, Tsoi S, Fan Y, Shi M, Ozaki R, Ma R, Luk A.
Multifaceted nature of young-onset diabetes - can genomic medicine improve the precision of diagnosis and management?
J Transl Genet Genom 2024;8:13-34. https://dx.doi.org/10.20517/jtgg.2023.36
Received: 2 Sep 2023 First Decision: 5 Dec 2023 Revised: 28 Dec 2023 Accepted: 9 Jan 2024 Published: 22 Jan 2024

Academic Editors: Brian Hon-Yin Chung, Sanjay Gupta Copy Editor: Fangyuan Liu Production Editor: Fangyuan Liu

Abstract
Young-onset type 2 diabetes (YOD), defined as diabetes diagnosis before age 40, has an aggressive clinical course
with premature mortality, in part due to long disease duration and lack of evidence to guide diagnosis and
management. Autoimmune type 1 diabetes, maturity-onset diabetes of the young (MODY), and latent autoimmune
diabetes in adults (LADA) are subtypes of diabetes in young people, which, however, cannot fully explain their
complex clinical course. Similarly, family members carrying the same rare genetic variant of monogenic diabetes
can have different presentations and outcomes. Ancestral heterogeneity, ecological transition, inter-ethnic
differences in genomic architecture, and variations in living environment, lifestyles, access to care, and timeliness
of diagnosis and treatment can influence the age of diagnosis and exposure to these cardiometabolic-renal risk
factors. Despite the wealth of literature on genetic associations with diabetes, the familial cosegregation of rare
variants and their relevance to YOD remains uncertain. This perspective was motivated by decades of clinical
observations and learnings from an ongoing randomized controlled trial that uses biogenetic markers to classify
patients with YOD for improving outcomes. Apart from highlighting the need to use family-based studies to
improve the precision of diagnosis, we discussed atypical causes for diabetic ketoacidosis and the importance of

© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0
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