Paediatric proteomic signatures of cardiometabolic disease-associated traits predict adult disease outcomes
While the earliest pathological signs of cardiovascular-kidney-metabolic disease (CKMD) emerge before age 20, current adult-based risk thresholds fail to identify a substantial fraction of children at high risk. With increasing childhood obesity, early, sensitive detection of CKMD risk is critical to timely intervention. We linked 25 CKMD phenotypes spanning liver, adipose, vascular and dysglycaemia traits to the circulating proteome in 273 Hispanic or Latino children and adolescents (13.1 ± 2.7 years; 53% female). Here we show that proteome signatures of CKMD in children are strongly associated with clinical CKMD outcomes in adults. In 685 adults from the same community and 28,256 adults from UK Biobank, we observe high concordance between the paediatric and adult CKMD phenotype-proteome relationships, related to pancreatic beta-cell health and insulin sensitivity, liver homeostasis, inflammation and cholesterol metabolism. Many proteins linked to paediatric CKMD were modifiable with glucagon-like peptide-1 receptor agonist therapy in adults and are linked to genetic liability to CKMD. These findings support an early origin of CKMD disease liability embedded in the human proteome in children, underscoring the value of precision prevention to forestall metabolic disease long before its clinical manifestation.
Authors
- Andrew Perry (ORCID: https://orcid.org/0000-0003-3342-6158)
- Jessica Sprinkles (ORCID: https://orcid.org/0009-0003-5731-7324)
- Ravi V. Shah (ORCID: https://orcid.org/0000-0002-4471-7156)
- Lauren E. Petty (ORCID: https://orcid.org/0000-0003-1619-6303)
- Jaclyn Tamaroff (ORCID: https://orcid.org/0000-0002-3630-9937)
- Eric Frankel (ORCID: https://orcid.org/0009-0001-4764-612X)
- Eric Farber‐Eger (ORCID: https://orcid.org/0000-0003-0281-3796)
- Penny Gordon‐Larsen (ORCID: https://orcid.org/0000-0001-5322-4188)
- Absalon Gutierrez (ORCID: https://orcid.org/0000-0002-5488-7028)
- Katie A. Meyer (ORCID: https://orcid.org/0000-0001-7490-5273)
- Alexandra B. Palmer
- Joshua M. Landman (ORCID: https://orcid.org/0000-0003-2431-6053)
- Jennifer E Below (ORCID: https://orcid.org/0000-0002-1346-1872)
- Quanhu Sheng (ORCID: https://orcid.org/0000-0001-8951-9295)
- Kristin L. Young (ORCID: https://orcid.org/0000-0003-0070-6145)
- Mariaelisa Graff (ORCID: https://orcid.org/0000-0001-6380-1735)
- Joseph B. McCormick (ORCID: https://orcid.org/0000-0002-5844-8102)
- Victoria L. Buchanan (ORCID: https://orcid.org/0000-0001-9943-9950)
- Jane E. Freedman (ORCID: https://orcid.org/0000-0002-0011-6164)
- Kari E. North (ORCID: https://orcid.org/0000-0002-8903-0366)
- Annie Green Howard (ORCID: https://orcid.org/0000-0003-0837-8166)
- Miryoung Lee (ORCID: https://orcid.org/0000-0003-4088-304X)
- Lindsay Fernández‐Rhodes (ORCID: https://orcid.org/0000-0001-6985-423X)
- Shilin Zhao (ORCID: https://orcid.org/0000-0002-3921-3965)
- Hung‐Hsin Chen (ORCID: https://orcid.org/0000-0002-1921-2797)
- Ting‐Chen Wang (ORCID: https://orcid.org/0000-0001-6139-3168)
- Heather M. Highland (ORCID: https://orcid.org/0000-0002-3583-8239)
- Alexander S Petty (ORCID: https://orcid.org/0009-0008-9366-7897)
- Kahraman Tanrıverdi (ORCID: https://orcid.org/0000-0002-1491-8803)
- Eric R. Gamazon (ORCID: https://orcid.org/0000-0003-4204-8734)
- Rashedeh Roshani (ORCID: https://orcid.org/0009-0001-2696-2852)
- Xinruo Zhang (ORCID: https://orcid.org/0000-0001-5789-4592)
- Anna Lorenz (ORCID: https://orcid.org/0009-0003-4344-7486)
- Ash Breidenbach (ORCID: https://orcid.org/0000-0003-3672-1128)
- Benjamin Lippi
- Alyssa Scartozzi
- Quinn Wells
- Matthew Nayor
- Mohammad Y. Anwar
- Susan P. Fisher-Hoch
- Wanying Zhu
- Mohanraj Krishnan
- Christine A. Ballard
Institutions
- Boston University (US)
- University of North Carolina at Chapel Hill (US)
- Vanderbilt University (US)
- Institute of Biomedical Sciences, Academia Sinica (TW)
- Neurobehavioral Systems (US)
- The University of Texas Health Science Center (US)
- Vanderbilt University Medical Center (US)
- The University of Texas Health Science Center at Houston (US)
Publication Details
- Journal
- Nature Metabolism
- Published
- 2026-09-11
- DOI
- https://doi.org/10.1038/s42255-026-01589-7
- Primary Topic
- Chronic Kidney Disease and Diabetes
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health