Chronic kidney disease is associated with attenuated plasma metabolome response to oral glucose tolerance testing

Open AccessPublished:October 18, 2022DOI:
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      CKD is associated with decreased anabolic response to insulin contributing to protein-energy wasting. Targeted metabolic profiling of oral glucose tolerance testing (OGTT) may help identify metabolic pathways contributing to disruptions to insulin response in CKD.


      Using targeted metabolic profiling, we studied the plasma metabolome response in 41 moderate-to-severe non-diabetic CKD patients and 20 healthy controls at fasting and 2 hours after an oral glucose load. We used linear mixed modeling with random intercepts, adjusting for age, sex, race/ethnicity, body weight and batch to assess heterogeneity in response to OGTT by CKD status.


      Mean eGFR among CKD participants was 38.9±12.7 ml/min per 1.73 m2 compared 87.2±17.7 ml/min per 1.73 m2 among controls. Glucose ingestion induced an anabolic response resulting in increased glycolysis products and a reduction in a wide range of metabolites including amino acids, TCA cycle intermediates, and purine nucleotides compared to fasting. Participants with CKD demonstrated a blunted anabolic response to OGTT evidenced by significant changes in 13 metabolites compared to controls. The attenuated metabolome response predominant involved mitochondrial energy metabolism, vitamin B family, and purine nucleotides. Compared to controls, CKD participants had elevated lactate: pyruvate (L:P) ratio and decreased GTP:GDP ratio during OGTT.


      Metabolic profiling of OGTT response suggests a broad disruption of mitochondrial energy metabolism in CKD patients. These findings motivate further investigation into the impact of insulin sensitizers and mitochondrial targeted therapeutics on energy metabolism in patients with non-diabetic CKD.