1133-P: Monogenic Diabetes in Chinese with Young-Onset Diabetes
Authors: TSOI SANDRA , LIM CADMON K.P. , MA RONALD C. , LAU ERIC S.H. , FAN BAOQI , CHOW ELAINE , KONG ALICE P. , CHAN JULIANA C. , LUK ANDREA 
Published: June 2021

Background: The clinical course of monogenic diabetes in Chinese is not well established. We determined the prevalence of mutation and variants of uncertain significance (VUS) in a panel of monogenic diabetes genes in a prospective cohort of Chinese with young-onset diabetes, and examined clinical characteristics and outcome of the affected individuals.
Methods: From patients enrolled in Hong Kong Diabetes Register between 1995-2012, DNA samples of 316 Chinese with non-type 1 diabetes diagnosed age &lt;40 years were sequenced. A targeted panel of 34 genes related to monogenic diabetes was designed with AmpliSeq (Illumina). Variants were interpreted based on American College of Medical Genetics and Genomics Standards and Guidelines. Incident complications including cardiovascular disease (CVD) and death were captured until 2019. Baseline characteristics and complications were compared between patients with and without pathogenic/ likely pathogenic variants or VUS.
Results: 24 (7.6%) patients had pathogenic/likely pathogenic variants and 39 (12.3%) had VUS in one or more monogenic diabetes genes. At baseline, patients with pathogenic/likely pathogenic variants had lower HbA1c (6.9 ± 1.0 vs. 7.9 ± 2.1%, p=0.02) and urine ACR (0.74 [0.44 - 2.03] vs. 1.71 [0.68 - 9.90] mg/mmol, p=0.01), and lower frequency of hypertension (20.8 vs. 46.9%, p=0.02) than those without mutation. Patients with and without VUS were similar for all characteristics. Over a median follow-up of 15.3 years, 4.3% of patients with pathogenic/likely pathogenic variants vs. 14.7% without mutation developed CVD (p=0.22), and 2.3% vs. 9.2% died (p=0.49). For patients with and without VUS, the frequencies were 14.7% vs. 14.7% (p=1.00) for incident CVD and 5.1% vs. 9.9% (p=0.55) for death.
Conclusion: One in five Chinese with young-onset diabetes had either mutation or VUS in monogenic diabetes genes. Patients with monogenic diabetes gene mutation had more favorable metabolic profile but did not differ in incident complication compared with those with no mutation.

Disclosure
S. Tsoi: None. C. K. P. Lim: Stock/Shareholder; Self; GemVCare Ltd. R. C. Ma: Other Relationship; Self; AstraZeneca, Medtronic, Research Support; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Tricida, Inc. E. S. H. Lau: None. B. Fan: None. E. Chow: Research Support; Self; Medtronic, Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Sanofi-Aventis. A. P. Kong: Advisory Panel; Self; Lilly Diabetes, Speaker’s Bureau; Self; Abbott, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Sanofi, Stock/Shareholder; Self; Aptorum. J. C. Chan: Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, MSD Corporation, Sanofi, Other Relationship; Self; Asia Diabetes Foundation, GemVCare, Research Support; Self; Applied Therapeutics, AstraZeneca, Hua Medicine, Lilly Diabetes, Merck KGaA. A. Luk: None.

Funding
Research Grants Council of Hong Kong (14114918); Research Impact Fund (R4012-18)