1829-PUB: Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes Randomised Controlled Trial (PRISM-RCT) in Chinese Patients with Young-Onset Diabetes—Study Design and Baseline Profile

Background: Young-onset diabetes (YOD) is heterogenous in aetiologies and clinical phenotypes. The PRISM study is a 3-year randomised controlled trial to evaluate the effect of precision treatment algorithm guided by biogenetic information on clinical outcomes in Chinese with YOD. Methods: In 2020-2021, we randomized 884 Chinese (18-50 years) with non-type 1 diabetes diagnosed ≤40 years to PRISM (n=443) or usual care (n=441). The PRISM group underwent assessment including biogenetic markers (anti-glutamic acid decarboxylase antibody [GADA], C-peptide, monogenic diabetes gene mutations and genetic risk scores predicting YOD, insulin requirement and complications) for issue of a personalized report to guide multidisciplinary care comprising endocrinologist consultation, counselling, empowerment on self-care, and reminders by supporting staff for 1 year at the Diabetes Research Centre before return to usual care. All patients return for assessment at year 3 for ascertainment of all-diabetes related endpoints. Results: Amongst 884 patients (mean±SD: age 40.7±6.5 years, median [IQR] age at diagnosis 34 [29,38] years, disease duration 7 [3,12] years, HbA1c 7.5±1.7%, 96.2% on glucose-lowering drugs, 27.7% on insulin), 74.7% had family history (19.7% both parents affected), 66.7% hypertension, 76.4% dyslipidaemia, 83% overweight and 35.4% albuminuria. Median fasting C-peptide was 0.6 (0.4, 0.9) nmol/L, 9.5% had C-peptide <0.2 nmol/L, 5.1% were GADA positive. In the PRISM group, 21.9% had low birthweight, 50.7%, childhood obesity, 5.7%, steroid exposure in childhood, 1.8-17.3%, co-existing endocrinopathies (thyroid disease, Cushing’s syndrome, polycystic ovarian syndrome), 7.5%, thalassaemia trait, 7.1%, chronic hepatitis B infection and 10.3%, mental illness. Conclusions: Lifecourse factors, endocrinopathies and mental illnesses are prevalent in YOD. Disclosure A.Luk: Research Support; Novo Nordisk, Boehringer-Ingelheim, Bayer Inc., Speaker's Bureau; Eli Lilly and Company. E.Chow: Research Support; Medtronic, Merck KGaA, Speaker's Bureau; Novartis, Bayer Inc., Sanofi. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Speaker's Bureau; Abbott, AstraZeneca, Lilly, Bayer Inc., Boehringer Ingelheim Inc. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer Inc., Celltrion, Boehringer Ingelheim and Eli Lilly Alliance, Sanofi, Research Support; AstraZeneca, Servier Laboratories, Viatris Inc., Hua Medicine, Merck KGaA, Applied Therapeutics Inc., Lee Powder, Pfizer Inc., Speaker's Bureau; Novartis, Stock/Shareholder; GemVCare Ltd. Y.Fan: None. B.Fan: None. C.K.P.Lim: Stock/Shareholder; GemVCare Ltd. E.S.H.Lau: None. E.W.M.Poon: None. S.T.F.Tsoi: None. R.Ozaki: None. R.C.Ma: Advisory Panel; AstraZeneca, Merck & Co., Inc., Other Relationship; Bayer Inc., Boehringer-Ingelheim, Research Support; Tricida, Inc., Roche Diagnostics, Novo Nordisk. Funding Health and Medical Research Fund (CFS-CUHK2)