Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes (PRISM): A Randomized Controlled Trial in Chinese Patients With Young-Onset Diabetes

Why clinicians should know about it

• Picked for Genetics (clinical) (top studies of the week, 18 October 2026): RCT using genetic markers for monogenic diabetes

Abstract

OBJECTIVE: Young-onset type 2 diabetes (YOD) results from complex causes, calling for precision management. RESEARCH DESIGN AND METHODS: The Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes (PRISM) study was a single-center, two-arm, 3-year randomized controlled trial in which Chinese individuals aged 18 to 50 years with non-type 1 diabetes diagnosed at age ≤40 years were randomly assigned to intervention (Joint Asia Diabetes Evaluation [JADE]-PRISM) or usual clinic-based care (JADE only). The intervention included technologically guided assessment and use of biogenetic markers (autoantibodies, C-peptide, and common and rare genetic variants) to classify diabetes for 1-year intensified, algorithm-based treatment followed by two annual reviews by an endocrinologist-led multidisciplinary team. The primary end point was a composite of incident or progression of all diabetes-related complications. Secondary end points included attainment of three or more treatment targets (HbA1c <6.2%, blood pressure <120/75 mmHg, LDL cholesterol <1.2 mmol/L, triglycerides <1.2 mmol/L, and waist circumference <80 [women] or <85 cm [men]), proxies of β-cell function, and patient-reported outcome measures (PROMs). RESULTS: During 2020 to 2021, 884 participants (mean [SD] age 40.7 [6.5] years; mean [SD] age at diagnosis 32.5 [6.8] years; autoantibody positivity [n = 46]; monogenic diabetes [n = 23]; C-peptide <200 pmol/L [n = 82]; central obesity [n = 699]; dyslipidemia [n = 669]; hypertension [n = 588]; albuminuria [n = 313]; insulin treated [n = 250]) were randomly assigned to the JADE-PRISM (n = 441) or JADE-only group (n = 443). During the 3-year study, the primary end point developed in 116 participants (26.3%) in the JADE-PRISM group versus 125 (28.2%) in the JADE-only group (odds ratio 0.908 [95% CI 0.675-1.221]). In the JADE-PRISM group, 104 participants (23.8%) versus 54 in the JADE-only group (12.2%; P < 0.001) reached three or more treatment targets, with improved proxies of β-cell function and reduced emotional distress. CONCLUSIONS: A 3-year technology-enhanced, multicomponent program improved cardiometabolic status, proxies of β-cell function, and PROMs in individuals with YOD but did not reduce complications.

Abstract as published, via PubMed.