Kidney Week

Abstract: FR-PO0535

Proteomic Signatures of Adiposity in Type 1 Diabetes Associated with Kidney Oxygenation

Session Information

• CKM: Clinical - Trials, Epidemiology, and Biomarkers
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Cardiovascular-Kidney-Metabolic Health

• 602 Cardiovascular-Kidney-Metabolic Health: Clinical

Authors

• Leidholt, Savanah L., University of Washington, Seattle, Washington, United States

Savanah L. Leidholt, PhD

• Nelson, Robert G., University of Washington, Seattle, Washington, United States

Robert G. Nelson, MD, PhD, FASN

• Miller, Kristen, University of Washington, Seattle, Washington, United States

Kristen Miller, MS

• Karihaloo, Anil K., Novo Nordisk Research Center Seattle, Seattle, Washington, United States

Anil K. Karihaloo, PhD

• de Boer, Ian, University of Washington, Seattle, Washington, United States

Ian de Boer, MD, MS

• Tommerdahl, Kalie L., University of Washington, Seattle, Washington, United States

Kalie L. Tommerdahl, MD, MS

• Goodrich, Jesse Allen, University of Southern California, Los Angeles, California, United States

Jesse Allen Goodrich, PhD

• D'Antonio, Matteo, University of Washington, Seattle, Washington, United States

Matteo D'Antonio, MS, MSc, PhD

• Choi, Ye Ji, University of Washington, Seattle, Washington, United States

Ye Ji Choi, MPH

• Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States

Matthias Kretzler, MD

• Schaub, Jennifer A., University of Michigan, Ann Arbor, Michigan, United States

Jennifer A. Schaub, MD

• Hodgin, Jeffrey B., University of Michigan, Ann Arbor, Michigan, United States

Jeffrey B. Hodgin, MD, PhD

• Menon, Rajasree, University of Michigan, Ann Arbor, Michigan, United States

Rajasree Menon, PhD

• McCown, Phillip J., University of Michigan, Ann Arbor, Michigan, United States

Phillip J. McCown, MS, PhD

• Eddy, Sean, University of Michigan, Ann Arbor, Michigan, United States

Sean Eddy, PhD

• Brosius, Chip, University of Arizona, Tucson, Arizona, United States

Chip Brosius, MD

• Alakwaa, Fadhl, University of Michigan, Ann Arbor, Michigan, United States

Fadhl Alakwaa, PhD

• Nair, Viji, University of Michigan, Ann Arbor, Michigan, United States

Viji Nair, PhD

• Naik, Abhijit S., University of Michigan, Ann Arbor, Michigan, United States

Abhijit S. Naik, MD, MPH, FASN

• Otto, Edgar A., University of Michigan, Ann Arbor, Michigan, United States

Edgar A. Otto, PhD

• Eichinger, Felix H., University of Michigan, Ann Arbor, Michigan, United States

Felix H. Eichinger

• Hartman, John R., University of Michigan, Ann Arbor, Michigan, United States

John R. Hartman

• Smith, Cathy, University of Michigan, Ann Arbor, Michigan, United States

Cathy Smith, PhD

• Bjornstad, Petter, University of Washington, Seattle, Washington, United States

Petter Bjornstad, MD

• Pyle, Laura, University of Washington, Seattle, Washington, United States

Laura Pyle, MS, PhD

Background

Obesity is increasingly common in type 1 diabetes (T1D) and may contribute to molecular and physiologic renal alterations before overt kidney disease. We identified adiposity-associated proteomic biomarkers linked to early kidney injury and oxygenation in T1D.

Methods

We performed proteomic profiling of individuals with T1D (n = 121) stratified by adiposity status; normal weight (NW), overweight (OW), and obese (OB). Participants were categorized using body mass index (BMI) for adults (>19 years) or BMI percentile for youth (<19 years). Adjusting for age, sex, and cohort, differentially expressed proteins (DEPs) were identified for all pairwise comparisons among T1D adiposity groups with false discovery rate control, followed by elastic net feature selection on pairwise DEPs. Within comparison groups, partial Spearman correlations evaluated associations between selected proteins and kidney outcomes, including urinary albumin-to-creatinine ratio (uACR), estimated glomerular filtration rate (eGFR), and kidney oxygenation (R2*) measured by blood oxygenation level dependent (BOLD) MRI.

Results

Participants included 62 NW, 37 OW, and 22 OB individuals with T1D (mean age 17 ± 4.06; 53% female). Selected proteins across adiposity comparisons associated with kidney oxygenation. Across all T1D adiposity groups, insulin-like growth factor-binding protein 1 & 2 (IGFBP1, IGFBP2) positively correlated with cortical and medullary oxygenation (r = 0.32–0.49; FDR p < 0.05). N-acetylgalactosamine-6-sulfatase (GALNS) and biglycan (BGN) were also positively associated with cortical oxygenation (r = 0.27–0.49; FDR p < 0.05), while leptin (LEP) and heart-type fatty acid binding protein (FABP3) were negatively associated (r = −0.33, −0.43; FDR p < 0.05). Results from the NW vs. OB comparison were similar, except FABP3 was not significant. No selected proteins were associated with clinical markers in NW vs. OW or OW vs. OB comparisons, and none were associated with eGFR or uACR in any analysis.

Conclusion

Adiposity in T1D was associated with distinct plasma proteomic patterns correlated with altered kidney oxygenation rather than traditional kidney function markers. Associations involving IGFBP1, IGFBP2, BGN, and LEP were most pronounced in individuals with obesity, highlighting potential roles for metabolic stress, extracellular matrix remodeling, and inflammatory signaling in early kidney physiologic alterations in T1D.