Kidney Week

Abstract: SA-PO1199

Differential Metabolomic Responses to Oral Glucose and Insulin Clamp Reveal Metabolic Alterations 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

An oral glucose tolerance test (OGTT) captures physiological responses involving gut absorption, incretin signaling, and endogenous insulin secretion, whereas the hyperinsulinemic–euglycemic clamp isolates insulin-mediated glucose uptake. We sought to characterize metabolic differences comparing the physiologic OGTT and the hyperinsulinemic testing of peripheral insulin sensitivity in CKD.

Methods

We used targeted plasma metabolomics to assess metabolic responses in 58 adults without diabetes (38 with CKD (eGFR <60 mL/min/1.73 m²) and 19 controls) from the Study of Glucose and Insulin in Renal Disease (SUGAR). Participants underwent a 75g OGTT approximately one week after a hyperinsulinemic–euglycemic clamp. A total of 88 metabolites were detected. Metabolite levels were normalized and log-transformed. Linear regression models adjusted for age, sex, race, and weight to test if the changes in metabolic response during hyperinsulinemic-euglycemic clamp is predicted by the changes during OGTT by CKD status.

Results

Participants with CKD had a mean (SD) eGFR of 39 (13) vs. 88 (18) ml/min/1.73m² in controls. A total of 9 metabolites (10%) showed differential responses to the OGTT and insulin clamp between CKD and controls. These differences mainly involved amino acid and energy metabolism, including valine, Asparagine, Alanine, and malonic acid.

Conclusion

CKD is associated with distinct plasma metabolomic responses to OGTT compared to insulin clamp, with differential alterations in amino acid metabolism. These findings suggest that impaired nutrient sensing and non-insulin-mediated pathways contribute to metabolic dysfunction in CKD.

Table 1. Comparison of plasma metabolite response during OGTT and insulin clamp by CKD status (n=58).

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025hkb4n874