, Volume 60, Issue 7, pp 1325–1332 | Cite as

Decreased basal hepatic glucose uptake in impaired fasting glucose

  • Mariam Alatrach
  • Christina Agyin
  • John Adams
  • Ralph A. DeFronzo
  • Muhammad A. Abdul-Ghani



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.


Hepatic 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.

Data availability

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.

Contribution statement

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.

Supplementary material

125_2017_4252_MOESM1_ESM.pdf (84 kb)
ESM Fig. 1 (PDF 84 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Mariam Alatrach
    • 1
  • Christina Agyin
    • 1
  • John Adams
    • 1
  • Ralph A. DeFronzo
    • 1
  • Muhammad A. Abdul-Ghani
    • 1
  1. 1.Diabetes DivisionUniversity of Texas Health Science Center at San AntonioSan AntonioUSA

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