Measuring Insulin Resistance in Humans

Abstract

Background: Insulin resistance is a pathophysiological condition associated with diabetes and cardiometabolic diseases that is characterized by a diminished tissue response to insulin action. Our understanding of this complex phenomenon and its role in the pathogenesis of cardiometabolic diseases is rooted in the discovery of insulin, its isolation and purification, and the challenges encountered with its therapeutic use.

Summary: In this historical perspective, we explore the evolution of the term "insulin resistance" and demonstrate how advances in insulin and glucose analytics contributed to the recognition and validation of this metabolic entity. We identify primary discoveries which were pivotal in expanding our knowledge of insulin resistance, the challenges in measurement and interpretation, contemporary techniques, and areas of future exploration. Key Message: Measurements of insulin resistance are important tools for defining and treating cardiometabolic diseases. Accurate quantification of this pathophysiological entity requires careful consideration of the assumptions and pitfalls of the methodological techniques and the historical and clinical context when interpreting and applying the results.

Keywords: History; Insulin action; Insulin assay; Insulin resistance; Insulin sensitivity.

Fig. 1

Effect of decreasing insulin sensitivity on blood glucose tolerance and the insulin glucose curve in a group of individuals with normal glucose tolerance (right panels) to those with diabetes (left panels). The series of panels shows the progressive effect of decreasing insulin sensitivity on the blood glucose concentrations (y axis). Each panel depicts the average glucose curve for individuals who underwent two tests: a 60min glucose tolerance test (solid lines) and a 60-min insulin glucose test (dashed lines). Adapted with permission from Himsworth [8].

Fig. 2

a Radiochromato-electrophoretograms of antiserum and insulin mixtures. Mixtures contained the same concentrations of guinea pig antibeef insulin serum and beef insulin-I131 but varying concentrations of human insulin as indicated. Adapted with permission from Yalow et al. [22]. b Ratio of bound insulin-I131 to free insulin-I131 as a function of concentration of added human insulin. The ratios were obtained from the complete series of radiochromato-electrophoretograms as shown in a. Adapted with permission from Yalow et al. [22].

Fig. 3

Plasma glucose and insulin responses of individuals with and without diabetes and obesity to glucose infusion to maintained diabetic blood glucose profiles. Left panel: 12 normal-weight (filled circles) and 12 obese without diabetes (open circles). Right panel: 12 normal-weight with diabetes (filled circles) and 11 obese without diabetes (open circles). Data represent mean ± standard errors. Adapted with permission from Perley et al. [32].