An in-silico proof-of-concept investigation of a combined glucose-insulin bolus quick dynamic insulin sensitivity test
The 30-min quick dynamic insulin sensitivity test (DISTq30) uses two blood-glucose measurements from a dynamic insulin sensitivity test protocol to provide low-cost, real-time insulin sensitivity (SI) measurements. However, the DISTq30 clinical protocol contains a potentially redundant 10-min period between glucose and insulin boluses that occur at t=0 and t=10min. A proposed protocol (DISTq20) reduces the DISTq30 test duration to 20min and administers a combined 10g glucose and 1U insulin bolus at t=0. The proposed protocol was evaluated against the clinically validated DISTq30 in a Monte Carlo analysis. 313 clinical responses to the dynamic insulin sensitivity and secretion tests (DISST) from three different studies were used to provide realistic parameter value sets. These values were used to create realistic in-silico responses to DISTq20 and DISTq30 protocols. Each simulated response was sampled at the appropriate times and SI was identified 200 times in a Monte Carlo analysis with added random assay error for each protocol and parameter set. In a second analysis, the DISTq20 response was simulated with 050% inhibition of the first phase insulin response to assess robustness to this potential effect. Simulated noise had a very similar effect on DISTq30 and DISTq20 SI values (R=0.99). DISTq20 overestimated DISTq30 SI by a median 1.7% (IQR ?4.3% to 7.3%). The second analysis showed that DISTq20 results were robust to variance in first phase insulin secretion (R=0.97). DISTq20 and DISTq30 both had a median CV of 7.9%. Inconsequential differences between SI values found by the DISTq30 and the DISTq20 in-silico indicate that the DISTq20 may produce similar clinical results to the DISTq30. Further analysis showed that the identification method was robust to the assumption of zero insulin suppression.
distq quick dynamic insulin sensitivity test distq20 20-minute distq distq30 30-minute distq im-ivgtt insulin modified intravenous glucose tolerance test disst dynamic insulin sensitivity and secretion test ogtt oral glucose tolerance test si insulin sensitivity un endogenous insulin production t2dm type 2 diabetes igt impaired glucose tolerance ifg impaired fasting glucose ngt normo-glucose tolerance