Glucose volume of distribution affects insulin sensitivity measured by intravenous glucose tolerance test

To determine whether glucose volume of distribution (Vd_GLUCOSE ) affects the diagnosis of impaired insulin sensitivity (IS) when using an intravenous glucose tolerance test (IVGTT).

Individuals with distinct levels of IS underwent IVGTT after an overnight fast. The prediabetic group (Prediab; n = 33) differed from the healthy group (Healthy; n = 14) in their larger glycosylated hemoglobin (HbA1c of 5.9 ± 0.3 vs. 5.4 ± 0.1%; 41 ± 4 vs. 36 ± 1 mmol/mol; p < 0.001), percent body fat (37 ± 6 vs. 24 ± 3%; p < 0.001) and cardiovascular fitness level (VO_2MAX 22 ± 5 vs. 44 ± 5 mL of O₂ ·kg^-1 ·min^-1 ; p < 0.001). Ten minutes after intravenous infusion of the glucose bolus (i.e., 35 g in a 30% solution), Vd_GLUCOSE was assessed from the increases in plasma glucose concentration. IS was calculated during the next 50 min using the slope of glucose disappearance and the insulin time-response curve.

Vd_GLUCOSE was higher in Healthy than in Prediab (230 ± 49 vs. 185 ± 21 mL·kg^-1 ; p < 0.001). Vd_GLUCOSE was a strong predictor of IS (β standardized coefficient 0.362; p = 0.004). VO_2MAX was associated with Vd_GLUCOSE and IS (Pearson r = 0.582 and 0.704, respectively; p < 0.001). However, body fat was inversely associated with Vd_GLUCOSE and IS (r = -0.548 and -0.555, respectively; p < 0.001).

Since fat mass is inversely related to Vd_GLUCOSE and in turn, Vd_GLUCOSE affects the calculations of IS, the IV glucose bolus dose should be calculated based on fat-free mass rather than body weight for a more accurate diagnosis of impaired IS.