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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 129

time, and frequent changes of care providers had made this approach challenging. The many technological
advances focusing on procedures have further contributed to the increasing organ-based and fragmented
[149]
healthcare practices .

Reducing genomic medicine to practice for improving the precision of diagnosis and therapy [150,151] must be
aligned with reform in undergraduate/professional education and practice environments to facilitate
[117]
implementation . Genomic medicine is only one of the many facets of person-orientated care which
begins with good history taking, physical examination, and value-based investigations. This should allow
physicians to prioritize a list of differential diagnoses followed by definitive or empirical treatment with
anticipated outcomes, and action plans if the outcome is not achieved. Doctors interested in the field of
diabetes need to stay abreast of the advances in genomic medicine, data analytics, and drug development
and learn how to use lay language to communicate probabilities, uncertainties, and complexities. They are
in the best position to assess the utility of using clinical/genetic risk scores or algorithms to segment patients
for targeted treatment, exclude hormonal or drug-induced forms of diabetes, and order comprehensive
genetic profiling to diagnose rare or syndromic forms of diabetes. For research-orientated physicians,
[152]
setting up registers will provide a powerful tool to assess the values of using new technologies and
approaches aimed at addressing the many needs of a young person with diabetes [17,101,153-155] . The adoption of
this person-orientated approach will bring back the science and arts of clinical medicine which is
particularly relevant to patients with YOD given the implications of misdiagnosis, misclassification, and
mismatched treatment.

PRISM: precision medicine to redefine insulin secretion and monogenic diabetes (PRISM) in
Chinese patients with young-onset diabetes
Complexity is a key feature in internal medicine. For the same disease, different people can have different
clinical presentations. For the same clinical presentation, different people can have different underlying
causes. For the same treatment, different people can have different responses. It is against this background
that the authors embarked upon a pragmatic 3-year RCT [Precision medicine to redefine insulin secretion
and monogenic diabetes (PRISM)] where 884 patients with type 2 diabetes diagnosed before the age of 40
and aged less than 50 years underwent structured clinical assessment and comprehensive biogenetic
profiling including measurement of HOMA-indices, CP, and GADA to diagnose LADA and assess beta-cell
function. These patients had genome-wide genotyping for computing polygenic risk scores for beta-cell
function and complications. They also had targeted gene-sequencing to detect mutations of genes for
MODY and monogenic diabetes. Other PROMs included psychosocial-behavioral factors and quality of life.
Half of these patients were randomized to receive 1-year intensive counseling and personalized treatment
guided by their biogenetic profiles and psychosocial needs, delivered by a specialist-led multidisciplinary
team in a diabetes center away from busy clinics aimed at attaining multiple treatment targets. After this
1-year multi-component management [154,156] , these patients will return to their usual clinics for follow-up
with yearly review at the diabetes center while the other half receive usual care. All patients will undergo re-
evaluation at 3 years. The primary outcome of PRISM is the incidence of all diabetes-related endpoints and
the secondary outcome is control of cardiometabolic risk factors https://clinicaltrials.gov/ct2/show/
NCT04049149. The results will be analyzed within the RE-AIM framework (Reach, Effectiveness, Adoption,
Implementation and Evaluation) to inform planners, practitioners, and policymakers about the
[157]
resources, infrastructure, personnel, logistics, and technology needed to reduce precision medicine in YOD
to practice and their cost-effectiveness. This project commenced in January 2020 and completed
recruitment in September 2021, and the 3-year study period will end in September 2024 .
[18]