Background: Prognosis of monogenic diabetes in Chinese is not well reported. We identified pathogenic mutations in monogenic diabetes genes in a prospective cohort of Chinese with young-onset diabetes, and compared the clinical characteristics and outcome between patients with and those without mutations.

Methods: From patients enrolled in the Hong Kong Diabetes Register between 1995-2012, DNA samples of 1021 Chinese with non-type 1 diabetes diagnosed ≤40 years old were sequenced. The custom targeted panel included 34 genes related to neonatal diabetes, maturity-onset diabetes of the young, syndromes associated with diabetes and severe insulin resistance. Variants were interpreted according to standard guidelines by ACMG. Patients were followed for incident complications until 2019.

Results: Pathogenic or likely pathogenic mutations in monogenic diabetes genes were detected in 33 (3.2%) patients. Mutations were more common in HNF1A (n=7) , GCK (n=6) and ABCC8 (n=5) genes. Mutation carriers had a higher female ratio (72.7 vs. 54.6%, p=0.05) and lower age at enrollment (37.9±10.6 vs. 41.5±10.4 years, p=0.05) but were similar age at diagnosis (31.5±7.3 vs. 33.1±6.0 years, p=0.13) and in diabetes duration (5.0[1.0-11.0] vs. 6.0[1.0-13.0] years, p=0.29) at baseline compared to non-carriers. Mutation carriers had lower BMI (23.6±3.5 vs. 26.0±4.8 kg/m2, p<0.01) , systolic blood pressure (119.4±14.9 vs. 125.6±17.4 mmHg, p=0.05) , HbA1c (7.3±1.3 vs. 7.9±2.0%, p=0.01) and triglyceride level (1.01[0.66-1.53] vs. 1.38[0.90-2.17] mmol/L, p=0.01) . Over a median follow-up of 17.1 years, (30.3%) patients with mutation vs. 369 (37.3%) without mutations developed cardiovascular disease, chronic or end-stage kidney disease and/or died (p=0.47) .

Conclusion: Around 3% of Chinese with young-onset non-type 1 diabetes had mutation in monogenic diabetes genes. Despite a more favorable metabolic profile, patients with mutation had similar incidence of diabetes complications to those without mutations.


S.Tsoi: None. C.K.Lim: None. R.C.Ma: Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc. E.S.Lau: None. B.Fan: None. E.Chow: Research Support; Hua Medicine, Medtronic, Powder Pharmaceuticals Inc., Speaker's Bureau; Novartis AG, Sanofi. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Other Relationship; AstraZeneca, Novo Nordisk, Research Support; Boehringer Ingelheim, Speaker's Bureau; AstraZeneca, Bayer, Eli Lilly and Company, Sanofi, Stock/Shareholder; Aptorum Group Limited. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Celltrion, Merck Sharp & Dohme Corp., Roche Diabetes Care, Viatris Inc., Research Support; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Hua Medicine, Servier Laboratories, Stock/Shareholder; GemVCare Ltd. A.Luk: None.


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

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