Nor Azlan Othman1, Paul D Docherty2, Jeremy D Krebs3, Damon A Bell4, J Geoffrey Chase2. 1. 1 Faculty of Electrical Engineering, Universiti Teknologi MARA (UiTM), Permatang Pauh, Penang, Malaysia. 2. 2 Department of Mechanical Engineering, Centre for Bio-Engineering, University of Canterbury, Christchurch, New Zealand. 3. 3 Department of Medicine, University of Otago, Wellington, New Zealand. 4. 4 School of Medicine and Pharmacology Royal Perth Hospital Unit, The University of Western Australia, Perth, Western Australia, Australia.
Abstract
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.
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.
Entities:
Keywords:
dynamic insulin sensitivity and secretion test; insulin resistance; intravenous glucose tolerance test; set point plasma glucose concentration; type 2 diabetes
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