Evaluation of the Performances and Costs of a Spectrum of DIST Protocols
The strategic design of most insulin sensitivity (SI) tests maximises either accuracy or economy, but not both. Hence, accurate, large-scale screening isn’t feasible. The DIST was developed to better optimize both important metrics. The highly flexible DIST protocol samples insulin, glucose and C-peptide during a comparatively short test. Varying the sampling periods and assays, and utilising alternative computational methods enables a wide range of tests with different accuracy and economy tradeoffs. The result is a hierarchy of tests to facilitate low-cost screening. Eight variations of the DIST are evaluated against the fully-sampled test by correlating the SI and endogenous insulin production (Uen(t)) metrics. Five variations include sample and assay reductions and three utilise DISTq parameter estimations. The DISTq identification methods only require glucose assays and thus enable real-time analysis. Three DISTq methods were tested; the fully-sampled, the Short, and the 30 minute two-sample protocol. 218 DIST tests were completed on 84 participants to provide the data for this study. Methods that assayed insulin replicated the findings of the full DIST particularly well (R=0.89~0.92) while those that assayed C-peptide managed to best replicate endogenous insulin metrics (R=0.72~1.0). The three DISTq protocols correlated to the fully-sampled DIST at R=0.83, 0.77 and 0.71 respectively. As expected, test resolution increased with rising protocol cost and intensity. The ability of significantly less expensive tests to replicate the values of the fully-sampled DIST was relatively high (R=0.92 with four glucose and two insulin assays and 0.71 with only two glucose assays). Thus, an SI screening programme could achieve high resolution at a low cost by using a lower resolution DIST test. When an individual’s result is close to a diagnostic threshold stored test samples could be re-assayed for more species to allow a higher resolution analysis without the need for a second invasive clinical test. Hence, a single test can lead to several outcomes with this hierarchy approach, enabling large scale screening with high resolution only where required with minimal and feasible economic cost and only a single invasive clinical procedure.