Renal Cortical Glucose Uptake Is Decreased in Insulin Resistance and Correlates Inversely With Serum Free-fatty Acids

Context: Studies on human renal metabolism are scanty. Nowadays, functional imaging allows the characterization of renal metabolism in a non-invasive manner. We have recently demonstrated that [18F]FDG-PET can be used to analyze renal glucose uptake rates (GU), and that the renal cortex is an insulin sensitive tissue.Objective: To confirm that renal GU is decreased in people with obesity, and to test whether circulating metabolites are related to renal GU.Design, setting and participants: 18 people with obesity and 18 non-obese controls were studied with [18F]FDG-PET during insulin clamp. Renal scans were obtained similar to 60 min after [18F]FDG injection. Renal GU was measured using fractional uptake rate and after correcting for residual intratubular [18F]FDG. Circulating metabolites were measured using high-throughput proton NMR metabolomics.Results: Cortical GU was higher in healthy non-obese controls compared to people with obesity (4.7 [3.4-5.6] vs 3.1 [2.2-4.3], p = 0.004, respectively), and it associated positively with the degree of insulin sensitivity (M value) (r = 0.42, p = 0.01). Moreover, cortical GU was inversely associated with circulating beta-OH-butyrate (r = -0.58, p = 0.009), acetoacetate (r = -0.48, p = 0.008), citrate (r = -0.44, p = 0.01) and free fatty acids (FFA) (r = -0.68, p < 0.0001), even when accounting for the M value. On the contrary, medullary GU was not associated with any clinical parameters.Conclusions: These data confirm differences in renal cortical GU between people with obesity and healthy non-obese controls. Moreover, the negative correlations between renal cortex GU and FFA, ketone bodies and citrate are suggestive of substrate competition in the renal cortex.