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

Abstract Aim 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). Methods 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 O 2 ·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. Results 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). Conclusions 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.