Diabetologia

, Volume 60, Issue 7, pp 1325–1332

Decreased basal hepatic glucose uptake in impaired fasting glucose

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

DOI: 10.1007/s00125-017-4252-0

Cite this article as:
Alatrach, M., Agyin, C., Adams, J. et al. Diabetologia (2017) 60: 1325. doi:10.1007/s00125-017-4252-0

Abstract

Aims/hypothesis

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).

Methods

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).

Results

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.

Conclusions/interpretation

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.

Keywords

Hepatic glucose production Hepatic glucose uptake Impaired fasting glucose 

Abbreviations

bEGP

Basal rate of endogenous glucose production

EGP

Endogenous glucose production

FPG

Fasting plasma glucose

HGU

Hepatic glucose uptake

IFG

Impaired fasting glucose

IGT

Impaired glucose tolerance

LBM

Lean body mass

NGT

Normal glucose tolerance

Ra

Rate of appearance

rEGP

Residual rate of endogenous glucose production

RaO

Rate of appearance of oral glucose

RaT

Total rate of appearance of glucose in the systemic circulation

Supplementary material

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

Funding information

Funder NameGrant NumberFunding Note
NIH grant (R01 DK097554-01) to MAG
  • NIH grant (R01 DK097554-01) to MAG

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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