Decreased non-insulin-dependent glucose clearance contributes to the rise in fasting plasma glucose in the nondiabetic range.
OBJECTIVE
To assess the contribution of decreased glucose clearance to the rise in fasting plasma glucose (FPG) in the nondiabetic range.


METHODS
A total of 120 subjects with normal glucose tolerance received an oral glucose tolerance test and euglycemic insulin clamp with 3-[(3)H]glucose. The basal and insulin-stimulated rates of glucose appearance, glucose disappearance, and glucose clearance and the basal hepatic insulin resistance index were calculated. Simple Pearson's correlation was used to assess the relationship between variables.


RESULTS
The increase in FPG (range 75-125 mg/dl) correlated (r = 0.32, P < 0.0001) with the increase in BMI (20-50 kg/m(2)). The fasting plasma insulin (FPI) concentration also increased progressively with the increase in BMI (r = 0.62, P < 0.0001). However, despite increasing FPI, the basal glucose clearance rate declined and correlated with the increase in BMI (r = -0.56, P < 0.0001). Basal hepatic glucose production (HGP) decreased with increasing BMI (r = -0.51, P < 0.0001) and correlated inversely with the increase in FPI (r = -0.32, P < 0.0001). The hepatic insulin resistance (basal HGP x FPI) increased with rising BMI (r = 0.52, P < 0.0001). During the insulin clamp, glucose disposal declined with increasing BMI (r = -0.64, P < 0.0001) and correlated with the basal glucose clearance (r = 0.39, P < 0.0001).


CONCLUSIONS
These results demonstrate that in nondiabetic subjects, rising FPG is associated with a decrease (not an increase) in basal hepatic glucose production and is explained by a reduction in glucose clearance.
Jani
Rucha
R
Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
Molina
Marjorie
M
Matsuda
Masafumi
M
Balas
Bogdan
B
Chavez
Alberto
A
DeFronzo
Ralph A
RA
Abdul-Ghani
Muhammad
M
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005215:Fasting; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin