Journal
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Volume 320, Issue 1, Pages E169-E177Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00397.2020
Keywords
disposition index; insulin secretion; insulin sensitivity; methodology
Categories
Funding
- Translation Core of the IU Diabetes Research Center Grant [2P30DK097512]
- NIH [T35HL110854]
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By linearizing the insulin secretion-sensitivity relationship, separate evaluation of the secretion-sensitivity slope and maximal insulin secretion is possible. This methodology provides an expanded understanding of treatment-induced changes compared with the disposition index when evaluating clinical trial data.
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 multivariate 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 treatmentinduced changes compared with 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. NEW & NOTEWORTHY The linearized insulin secretion-sensitivity relationship allows separate evaluation of the secretion-sensitivity slope and of maximal insulin secretion. Here, we demonstrate the application of this methodology to the evaluation of clinical trial data, showing that it provides an expanded understanding of treatment-induced changes compared with the disposition index.
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