Abstract
BACKGROUND: Physiological models that are used with dynamic test data to assess insulin sensitivity (SI) assume that the metabolic target glucose concentration ( G(TARGET)) is equal to fasting glucose concentration ( G(0)). However, recent research has implied that irregularities in G(0) in diabetes may cause erroneous SI values. This study quantifies the magnitude of these errors. METHODS: A clinically validated insulin/glucose model was used to calculate SI with the standard fasting assumption (SFA) G(0) = G(TARGET). Then G(TARGET) was treated as a variable in a second analysis (VGT). The outcomes were contrasted across twelve participants with established type 2 diabetes mellitus that were recruited to take part in a 24-week dietary intervention. Participants underwent three insulin-modified intravenous glucose tolerance tests (IM-IVGTT) at 0, 12, and 24 weeks. RESULTS: SI(VGT) had a median value of 3.36×10(-4) L·mU(-1)·min(-1) (IQR: 2.30 - 4.95×10(-4)) and were significantly lower ( P < .05) than the median SI(SFA) (6.38×10(-4) L·mU(-1)·min(-1), IQR: 4.87 - 9.39×10(-4)). The VGT approach generally yielded lower SI values in line with expected participant physiology and more effectively tracked changes in participant state over the 24-week trial. Calculated G(TARGET) values were significantly lower than G(0) values (median G(TARGET) = 5.48 vs G(0) = 7.16 mmol·L(-1) P < .001) and were notably higher in individuals with longer term diabetes. CONCLUSIONS: Typical modeling approaches can overestimate SI when G(TARGET) does not equal G(0). Hence, calculating G(TARGET) may enable more precise SI measurements in individuals with type 2 diabetes, and could imply a dysfunction in diabetic metabolism.