| Summary: | Background: Physiological models that are used with dynamic test data to assess insulin sensitivity (SI) assume that the metabolic target glucose concentration (GTARGET) 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. Methods: A clinically validated insulin/glucose model was used to calculate SI with the standard fasting assumption (SFA) G0 = GTARGET. Then GTARGET 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: SIVGT 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 SISFA (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 GTARGET values were significantly lower than G0 values (median GTARGET = 5.48 vs G0 = 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 GTARGET does not equal G0. Hence, calculating GTARGET may enable more precise SI measurements in individuals with type 2 diabetes, and could imply a dysfunction in diabetic metabolism. © 2018, © 2018 Diabetes Technology Society.
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