Kidney Week

Abstract: SA-PO1200

Association of Incretin Response to Oral Glucose Challenge with Altered Plasma Metabolomic Profile in CKD

Session Information

• CKD: Biomarkers and Emerging Tools for Diagnosis and Monitoring
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Ahmadi, Armin, University of California San Diego, La Jolla, California, United States

Armin Ahmadi, PhD

• Fan, Sili, University of California Davis, Davis, California, United States

Sili Fan

• Zelnick, Leila R., University of Washington, Seattle, Washington, United States

Leila R. Zelnick, PhD

• Gamboa, Jorge, University of Alabama at Birmingham Health System Authority, Birmingham, Alabama, United States

Jorge Gamboa, MD, PhD

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

Ian de Boer, MD, MS

• Cummings, Bethany P., University of California Davis, Davis, California, United States

Bethany P. Cummings, PhD, DVM

• Roshanravan, Baback, University of California Davis, Davis, California, United States

Baback Roshanravan, MD, MS, MPH, FASN

Background

While glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are key regulators of postprandial insulin secretion, their metabolic consequences in CKD remain poorly understood. In this study we aimed to examine the link between incretin response and glucose metabolism during an oral glucose tolerance test (OGTT).

Methods

We examined plasma metabolomic responses during a 75-g OGTT in 38 participants with non-diabetic CKD (eGFR <60 mL/min/1.73 m²) and 19 matched healthy controls from the Study of Glucose and Insulin in Renal Disease (SUGAR). We quantified the total area under the curve (tAUC) for plasma GLP-1 and GIP and profiled 88 plasma metabolites using targeted metabolomics. Data were normalized and log-transformed. Associations between incretin tAUC and metabolite changes were assessed using linear regression adjusting for age, sex, race/ethnicity, and body weight, and tested for interaction by CKD status.

Results

The mean (SD) eGFR was 39 (13) mL/min/1.73 m² in CKD participants and 88 (18) mL/min/1.73 m² in controls. Overall, 6 metabolites showed significant interactions with GIP and 12 with GLP-1. In CKD, incretin responses were associated with blunted or inverse changes in these metabolites primarily involved in amino acid metabolism, the TCA cycle, and purine/pyrimidine pathways (Table 1).

Conclusion

In CKD, altered incretin responses are linked to distinct plasma metabolomic signatures during OGTT mainly involving amino acid and energy metabolism. These findings suggest that incretin-mediated pathways may contribute to the pathophysiology of metabolic dysregulation in CKD.

Table 1. The association of incretin response with plasma metabolome changes in response to OGTT by CKD status (n=57).

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.20259vdva7jn