The Need to Calculate Target Glucose Levels When Measuring Changes in Insulin Sensitivity During Interventions for...

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 ( G₀). However, recent research has implied that irregularities in G₀ in diabetes may cause erroneous SI values. This study quantifies the magnitude of these errors.

A clinically validated insulin/glucose model was used to calculate SI with the standard fasting assumption (SFA) G₀ = 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.

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 G₀ values (median G_TARGET = 5.48 vs G₀ = 7.16 mmol·L^-1 P < .001) and were notably higher in individuals with longer term diabetes.

Typical modeling approaches can overestimate SI when G_TARGET does not equal G₀. Hence, calculating G_TARGET may enable more precise SI measurements in individuals with type 2 diabetes, and could imply a dysfunction in diabetic metabolism.