Abstract

Objective: To assess the contribution of decreased glucose clearance to the rise in fasting plasma glucose (FPG) in the non-diabetic range.

Research Design and Methods: 120 subjects with normal glucose tolerance received an OGTT and euglycemic insulin clamp with 3-[³H] glucose. The basal and insulin-stimulated rates of glucose appearance, glucose disappearance, glucose clearance, and basal hepatic insulin resistance index were calculated. Simple Pearson correlation was used to assess the relationship between variables.

Results: The increase in FPG (range= 75 to 125 mg/dl) correlated (r=0.32, p<0.0001) with the increase in BMI (range = 20-50 kg/m²). The fasting plasma insulin concentration (FPI) 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 × 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).

Conclusion: These results demonstrate that, in non-diabetic 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.