Insulin Effectiveness, a Measure Consisting of Insulin Sensitivity, Secretion, and Clearance, Captures Differences Between Diabetic and Nondiabetic States

Abstract

OBJECTIVEInsulin clearance is implicated in regulation of glucose homeostasis independently of insulin sensitivity and insulin secretion. To understand the relation between blood glucose levels and insulin sensitivity, insulin secretion, and insulin clearance, we performed a mathematical analysis.RESEARCH DESIGN AND METHODSWe performed a hyperglycemic clamp, a hyperinsulinemic-euglycemic clamp, and an oral glucose tolerance test in 47, 16, and 49 subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM), respectively.RESULTSThe disposition index (DI), defined as the product of insulin sensitivity and insulin secretion and regarded as a measure of the capacity for glucose handling, did not well explain blood glucose levels at the early stage of glucose intolerance. 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 “insulin effectiveness,” that is based on this equation and corresponds to DI divided by the square of insulin clearance. Insulin effectiveness 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.CONCLUSIONSInsulin effectiveness, which likely reflects insulin action in the body, well represents changes in glycemia and is impaired during the transition from IGT to T2DM. It may serve as a new indicator for the trajectory of changes in glucose tolerance.