Decreased basal hepatic glucose uptake in impaired fasting glucose.
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.
Diabetes Division, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA.
Mariam
M
Alatrach
Diabetes Division, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA.
Christina
C
Agyin
Diabetes Division, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA.
John
J
Adams
Diabetes Division, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA.
Ralph A
RA
DeFronzo
Diabetes Division, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA. abdulghani@uthscsa.edu.
Muhammad A
MA
Abdul-Ghani
D000284:Administration, Oral; D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D001835:Body Weight; D005260:Female; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D011236:Prediabetic State / Q000097:blood; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose
Hepatic glucose production; Hepatic glucose uptake; Impaired fasting glucose