Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial (PRISM-RCT) in Chinese patients with young-onset diabetes: design, methods and baseline characteristics

Abstract

Introduction: We designed and implemented a patient-centered, data-driven, holistic care model with evaluation of its impacts on clinical outcomes in patients with young-onset type 2 diabetes (T2D) for which there is a lack of evidence-based practice guidelines.

Research design and methods: In this 3-year Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial, we evaluate the effects of a multicomponent care model integrating use of information and communication technology (Joint Asia Diabetes Evaluation (JADE) platform), biogenetic markers and patient-reported outcome measures in patients with T2D diagnosed at ≤40 years of age and aged ≤50 years. The JADE-PRISM group received 1 year of specialist-led team-based management using treatment algorithms guided by biogenetic markers (genome-wide single-nucleotide polymorphism arrays, exome-sequencing of 34 monogenic diabetes genes, C-peptide, autoantibodies) to achieve multiple treatment goals (glycated hemoglobin (HbA1c) <6.2%, blood pressure <120/75 mm Hg, low-density lipoprotein-cholesterol <1.2 mmol/L, waist circumference <80 cm (women) or <85 cm (men)) in a diabetes center setting versus usual care (JADE-only). The primary outcome is incidence of all diabetes-related complications.

Results: In 2020-2021, 884 patients (56.6% men, median (IQR) diabetes duration: 7 (3-12) years, current/ex-smokers: 32.5%, body mass index: 28.40±5.77 kg/m², HbA1c: 7.52%±1.66%, insulin-treated: 27.7%) were assigned to JADE-only (n=443) or JADE-PRISM group (n=441). The profiles of the whole group included positive family history (74.7%), general obesity (51.4%), central obesity (79.2%), hypertension (66.7%), dyslipidemia (76.4%), albuminuria (35.4%), estimated glomerular filtration rate <60 mL/min/1.73 m² (4.0%), retinopathy (13.8%), atherosclerotic cardiovascular disease (5.2%), cancer (3.1%), emotional distress (26%-38%) and suboptimal adherence (54%) with 5-item EuroQol for Quality of Life index of 0.88 (0.87-0.96). Overall, 13.7% attained ≥3 metabolic targets defined in secondary outcomes. In the JADE-PRISM group, 4.5% had pathogenic/likely pathogenic variants of monogenic diabetes genes; 5% had autoantibodies and 8.4% had fasting C-peptide <0.2 nmol/L. Other significant events included low/large birth weight (33.4%), childhood obesity (50.7%), mental illness (10.3%) and previous suicide attempts (3.6%). Among the women, 17.3% had polycystic ovary syndrome, 44.8% required insulin treatment during pregnancy and 17.3% experienced adverse pregnancy outcomes.

Conclusions: Young-onset diabetes is characterized by complex etiologies with comorbidities including mental illness and lifecourse events.

Trial registration number: NCT04049149.

Keywords: MODY; genetics; latent autoimmune diabetes in adults; randomized controlled trials as topic.

Figure 1

The treatment algorithm for patients randomized to the Joint Asia Diabetes Evaluation-Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes group who were given biogenetic information to guide personalized therapies to achieve multiple strict metabolic goals during the 1-year intensive intervention at Diabetes and Endocrine Research Center. ASA, Asian specific array; BMI, body mass index; CP, C-peptide; DPP4i, dipeptidyl peptidase-4 inhibitor; GADA, glutamic acid decarboxylase antibody; GRS, genetic riskscore; GLP-1 RA, glucagon-like peptide-1 receptor agonist; HNF, Hepatic nuclear factor; LDL-cholesterol, low-density lipoprotein-cholesterol; OAD, oral anti-diabetic drugs; SGLT2i, sodium-glucose co-transporter 2 inhibitor; SNP, single-nucleotide polymorphism.

Figure 2

Graphical representation of the Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial (PRISM-RCT) study. JADE, Joint Asia Diabetes Evaluation; GADA, glutamic acid decarboxylase antibodies; GRS, genetic risk score; YOD, young-onset diabetes; HbA1c, glycated hemoglobin; BP, blood pressure; LDL-C, low-density lipoprotein cholesterol; WC, waist circumference; ASCVD, atherosclerotic cardiovascular disease; DERC, Diabetes and Endocrine Research Center. Constructed by Microsoft PowerPoint, graphics are either original or from Microsoft Office stock.