The Linearized Disposition Index Augments Understanding of Treatment Effects in Diabetes.

The Disposition Index, calculated by multiplying measures of insulin secretion and insulin sensitivity, is widely applied as a sensitivity-adjusted measure of insulin secretion. We have recently shown that linearizing the underlying relationship uniquely permits identification of terms relating to maximal insulin secretion capacity and the secretion-coupling relationship, with both terms separately contributing to differences in the secretion-sensitivity relationship across gradations of glycemia. Here we demonstrate the application of this linearized equation to the evaluation of treatment-induced changes in the insulin secretion-sensitivity relationship. We applied a combination of repeated measures multivariable linear regression (evaluating treatment-induced changes in the joint relationship of insulin sensitivity and secretion) plus mixed model repeated measures (evaluating treatment effects on maximal secretion capacity and on the secretion-sensitivity coupling slope), and compared against a usual application of the disposition index calculated from the same measurements. This novel approach allows a more informative description of treatment-induced changes compared to the usual disposition index, including isolating the source of change within the mutually adjusted relationship, and identifying treatment-induced changes in the secretion-sensitivity coupling slope and in maximal insulin secretion. Application of this linearized approach provides an expanded understanding of treatment-induced changes in the insulin sensitivity-secretion relationship.