Correction of glucose carbon recycling for the determination of ‘true’ hepatic glucose production rates by (1-13C1)glucose

Abstract

Hepatic glucose production (HGP) and glucose carbon recycling are traditionally estimated by the combined use of hydrogen and carbon‐labeled glucose tracers. A single‐isotope method such as that of Reichard et al. for the determination of HGP and glucose carbon recycling requires the determination of activities in different glucose carbons by chemical degradation. Since the ¹³C content in the glucose carbon skeleton can be determined from mass fragmentography, the use of ¹³C‐labeled glucose and mass fragmentography can provide a single‐isotope method for the quantification of the recycled carbons. Correction for the recycling makes it possible to determine the true HGP. In this study, (1‐¹³C₁)glucose and mass fragmentography were used for the determination of HGP and glucose carbon recycling in six colon cancer patients. Molar enrichment of the molecular ion (m/z 328 cluster of glucose aldonitrile pentaacetate) was used to determine ‘unconnected’ HGP, which was 1.93 ± 0.11 mg kg⁻¹ min⁻¹ (mean ± s.e.m.). The difference in molar enrichment of the molecular ion C1‐C6 (m/z 328) and the ion corresponding to C1‐C4 fragment (m/z 242) was used to determine the contribution of recycled label carbon. After this correction, the ‘corrected’ HGP was 2.04 ± 0.12 mg kg⁻¹ min⁻¹, which is not significantly different from the ‘true’ HGP rate of 2.05 ± 0.15 mg kg⁻¹ min⁻¹ determined by using (6‐³H)glucose. HGP determined from the enrichment of the molecular ion C1‐C6 underestimates true HGP, as expected. The corrected HGPs correlate well with those from 6‐³H method (r = 0.86, y = 1.06x − 0.12; p < 0.01). Calculated isotope carbon recycling determined as the difference between the uncorrected and the (6‐³H)HGP is 4.5 ± 4.8% and is comparable to the 5.0 ± 3.3% determined by mass fragmentography. The use of (1‐¹³C₁)glucose tracer and measurement of recycling by mass fragmentography therefore provide a single‐label, non‐radioactive method for the determination of HGP rates.