A simple intravenous glucose tolerance test for assessment of insulin sensitivity

Abstract

Background: The aim of the study was to find a simple intravenous glucose tolerance test (IVGTT) that can be used to estimate insulin sensitivity.

Methods: In 20 healthy volunteers aged between 18 and 51 years (mean, 28) comparisons were made between kinetic parameters derived from a 12-sample, 75-min IVGTT and the M(bw) (glucose uptake) obtained during a hyperinsulinemic euglycemic glucose clamp. Plasma glucose was used to calculate the volume of distribution (V(d)) and the clearance (CL) of the injected glucose bolus. The plasma insulin response was quantified by the area under the curve (AUC(ins)). Uptake of glucose during the clamp was corrected for body weight (M(bw)).

Results: There was a 7-fold variation in M(bw). Algorithms based on the slope of the glucose-elimination curve (CL/V(d)) in combination with AUC(ins) obtained during the IVGTT showed statistically significant correlations with M(bw), the linearity being r(2) = 0.63-0.83. The best algorithms were associated with a 25-75th prediction error ranging from -10% to +10%. Sampling could be shortened to 30-40 min without loss of linearity or precision.

Conclusion: Simple measures of glucose and insulin kinetics during an IVGTT can predict between 2/3 and 4/5 of the insulin sensitivity.

Figure 1

Plasma concentrations during the IVGTT. Plasma glucose above baseline (A) and the plasma insulin (B) and C-peptide concentrations (C) during 20 intravenous glucose tolerance tests (IVGTTs). The thin lines represent one experiment. The thick line in A is the modelled average curve, based on the kinetic data shown in Table 1, while B and C are the mean for each point in time.

Figure 2

Insulin resistance as given by the glucose clamp and a short IVGTT. (A) The relationship between M_bw of the hyperinsulinemic euglycemic clamp and a surrogate expression for insulin sensitivity based on the half-life of glucose and the area under the curve (AUC) for plasma insulin during a 75-min IVGTT in 20 volunteers. (B) Same equation but using only baseline plasma glucose and insulin concentrations. (C) M_bw versus insulin sensitivity obtained by "minimal model" (MINMOD) analysis.

Figure 3

Insulin resistance by the glucose clamp and a short IVGTT. The relationship between M_bw and various combinations of the clearance (CL) and volume of distribution (V_d) of glucose and (A, B) the area under the curve for plasma insulin (AUC_ins) during the 75-min IVGTT, or (C) using the mean plasma insulin level measured at 10, 20, 30, and 40 min.