DI/cle, a Measure Consisting of Insulin Sensitivity, Secretion, and Clearance, Captures Diabetic States

ABSTRACT Context Insulin clearance is implicated in regulation of glucose homeostasis independently of insulin sensitivity and insulin secretion. Objective To understand the relation between blood glucose and insulin sensitivity, secretion, and clearance. Methods We performed a hyperglycemic clamp, a hyperinsulinemic-euglycemic clamp, and an oral glucose tolerance test (OGTT) in 47, 16, and 49 subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM), respectively. Mathematical analyses were retrospectively performed on this dataset. Results The disposition index (DI), defined as the product of insulin sensitivity and secretion, showed a weak correlation with blood glucose levels, especially in IGT ( r = 0.04; 95% CI, −0.63– 0.44). However, an equation relating DI, insulin clearance, and blood glucose levels was well conserved regardless of the extent of glucose intolerance. As a measure of the effect of insulin, we developed an index, designated “DI/cle,” that is based on this equation and corresponds to DI divided by the square of insulin clearance. DI/cle was not impaired in IGT compared with NGT, possibly as a result of a decrease in insulin clearance in response to a reduction in DI, whereas it was impaired in T2DM relative to IGT. Moreover, DI/cle estimated from a hyperinsulinemic-euglycemic clamp, OGTT, or a fasting blood test were significantly correlated with that estimated from two clamp tests ( r = 0.52; 95% CI, 0.37– 0.64, r = 0.43; 95% CI, 0.24– 0.58, and r = 0.54; 95% CI, 0.38– 0.68, respectively). Conclusions DI/cle can serve as a new indicator for the trajectory of changes in glucose tolerance.