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

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 to 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 disposition index(/clearance), (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 2 clamp tests (r = 0.52; 95% CI, 0.37 to 0.64, r = 0.43; 95% CI, 0.24 to 0.58, r = 0.54; 95% CI, 0.38 to 0.68, respectively). CONCLUSION: DI(/cle) can serve as a new indicator for the trajectory of changes in glucose tolerance.