Decreased basal hepatic glucose uptake in impaired fasting glucose
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This research aimed to define the pathophysiological defects responsible for the elevated fasting plasma glucose (FPG) concentration and excessive rise in post-load plasma glucose observed in individuals with impaired fasting glucose (IFG).
We used tracer techniques to quantify basal splanchnic (primarily hepatic) glucose uptake and glucose fluxes following glucose ingestion in individuals with normal glucose tolerance (NGT; n = 10) and IFG (n = 10).
Individuals with IFG had a comparable basal rate of hepatic glucose production to those with NGT (15.2 ± 0.2 vs 18.0 ± 0.8 μmol min−1 [kg lean body mass (LBM)]−1; p = 0.09). However, they had a significantly reduced glucose clearance rate during the fasting state compared with NGT (2.64 ± 0.11 vs 3.62 ± 0.20 ml min−1 [kg LBM]−1; p < 0.01). The difference between the basal rate of glucose appearance measured with [3-3H]glucose and [1-14C]glucose, which represent basal splanchnic glucose uptake, was significantly reduced in IFG compared with NGT (1.39 ± 0.28 vs 3.16 ± 0.44 μmol min−1 [kg LBM]−1; p = 0.02). Following glucose ingestion, the total amount of exogenous glucose that appeared in the systemic circulation was not significantly different between groups. However, suppression of endogenous glucose production (EGP) was markedly impaired in individuals with IFG.
These results demonstrate that decreased tissue (liver) glucose uptake, not enhanced EGP, is the cause for elevated FPG concentration in individuals with IFG, while the excessive rise in plasma glucose concentration following a glucose load in these individuals is the result of impaired suppression of hepatic glucose production.
KeywordsHepatic glucose production Hepatic glucose uptake Impaired fasting glucose
Basal rate of endogenous glucose production
Endogenous glucose production
Fasting plasma glucose
Hepatic glucose uptake
Impaired fasting glucose
Impaired glucose tolerance
Lean body mass
Normal glucose tolerance
Rate of appearance
Residual rate of endogenous glucose production
Rate of appearance of oral glucose
Total rate of appearance of glucose in the systemic circulation
We thank L. Albarado and S. Balmer from the Diabetes Division, UTHSCSA (San Antonio, TX, USA), for their expert secretarial assistance in preparation of the manuscript. R. DeFronzo’s salary is supported, in part, by the South Texas Veterans Health Care System. We would also like to thank CORPAK MedSystem (Buffalo Grove, IL, USA) for providing the CORTRAK instrument for placing the nasoduodenal tube.
The data will be made available once the study has been completed.
This study was supported by a National Institutes of Health (NIH) grant (R01 DK097554-01) to MAG.
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
MA, CA, and JA participated in the discussion about the design of the study, generated the data, contributed to drafting the article and approved the final version. MAG designed the study, wrote the protocol, contributed to data generation and data analysis, wrote the manuscript and approved the final version. RAD reviewed and revised the study protocol, participated in the discussion about data interpretation, revised the manuscript and approved the final version. MAG is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
- 14.Polidori D, Sha S, Mudaliar S et al (2013) Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: results of a randomized, placebo-controlled study. Diabetes Care 36:2154–2161CrossRefPubMedPubMedCentralGoogle Scholar
- 26.RA DF Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 37(667–687):1988Google Scholar