Abstract: TH-PO1210
Progression of Cardio-Kidney-Metabolic Syndrome in Adolescents with Type 2 Diabetes
Session Information
- Late-Breaking Research Posters
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1602 Hypertension and CVD: Clinical
Authors
- Pyle, Laura, University of Washington, Seattle, Washington, United States
- Pinzon Cortes, Jairo Arturo, University of Washington, Seattle, Washington, United States
- Choi, Ye Ji, University of Washington, Seattle, Washington, United States
- Narongkiatikhun, Phoom, University of Washington, Seattle, United States
- Karihaloo, Anil K., Novo Nordisk A/S, Bagsværd, Capital Region of Denmark, Denmark
- Bansal, Nisha, University of Washington, Seattle, Washington, United States
- Kanter, Jenny E., University of Washington, Seattle, Washington, United States
- Bornfeldt, Karin, University of Washington, Seattle, Washington, United States
- Tuttle, Katherine R., Providence Health and Services, Renton, Washington, United States
- de Boer, Ian, University of Washington, Seattle, Washington, United States
- Sharma, Kumar, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Waikar, Sushrut S., Boston University, Boston, Massachusetts, United States
- van Raalte, Daniël H., Amsterdam UMC Locatie AMC, Amsterdam, NH, Netherlands
- Gubitosi-Klug, Rose, University Hospitals Rainbow Babies & Children's Hospital, Cleveland, Ohio, United States
- Tommerdahl, Kalie L., University of Washington, Seattle, Washington, United States
- Bjornstad, Petter, University of Washington, Seattle, Washington, United States
Background
Cardiovascular-kidney-metabolic (CKM) syndrome, defined by the American Heart Association and advanced through its 2024 CKM Health Initiative in collaboration with ASN, integrates risk across metabolic, kidney, and cardiovascular systems. Youth onset type 2 diabetes (YOT2D) carries a heavy complication burden by young adulthood.
Methods
We followed 699 participants with YOT2D in TODAY/TODAY2 for up to 15 years. TODAY randomized youth to treatment with metformin, metformin+intensive lifestyle, or metformin+rosiglitazone; TODAY2 provided long term observational follow up. Surveillance included adjudicated cardiovascular events; UACR and eGFR; carotid femoral pulse wave velocity (cf PWV); B type natriuretic peptide (BNP); and echocardiography. CKM stages were assigned annually per AHA criteria (all ≥2 with diabetes); Stage 3: cf PWV>10 m/s, BNP>80 pg/mL, or KDIGO very high risk; Stage 4: cardiovascular event or echocardiographic HFpEF. Time to progression was the first transition to a higher stage. Baseline plasma SomaScan proteomics (~7,000 proteins) were available in 374 participants. Associations were tested using Cox and elastic net Cox with 5% false discovery rate (FDR); discrimination by Harrell’s C.
Results
Baseline age 14±2 years; 35% male; BMI Z 2.2±0.4; T2D duration 7±5 months. Over 13.3±1.8 years of follow-up, 43.9% experienced CKM progression, with 24.3% reaching Stage 3 and 5.3% Stage 4. Original TODAY treatment assignment and other clinical variables were not associated with time to progression (all p>0.05; C=0.49–0.56). In proteomic analyses, plasma Hepatocyte Cell Adhesion Molecule 2 (HEPACAM2) was associated with faster progression after FDR correction (q=0.008); 546 proteins were nominally associated (p<0.05). Elastic net Cox selected 50 proteins and improved discrimination (C=0.77 vs 0.57 for clinical only models).
Conclusion
Adolescents with YO T2D entering young adulthood carried a striking CKM burden and high progression rates. Protein based risk models, led by HEPACAM2, substantially outperformed clinical variables; initial TODAY treatment allocation did not influence CKM trajectory.
Funding
- NIDDK Support