Measuring Insulin ActionIn Vivo

Abstract

The goal to accurately measure insulin sensitivity (i.e., “insulin resistance”) in patients remains an important goal. Insulin resistance is a risk factor for a plethora of chronic diseases (diabetes cardiovascular disease, hypertension, colon cancer). To study these diseases and to intervene early in their pathogenesis requires that we quantify risk factors and insulin resistance is one important candidate. To accurately measure sensitivity it is important to use a method that observes in some fashion the metabolic effect of insulin given intravenously . Thus, the glucose clamp and the minimal model are accurate and reproducible methods. One must remain vigilant regarding limitations of these methods. However, they may be applied with confidence under a wide variety of conditions. Unfortunately it is not possible to recommend simpler (i.e. surrogate) methods that can be applied with confidence. While it might be appropriate to use fasting insulin to reflect insulin resistance in patients without any degree of β‐cell failure, it is usually not possible to determine a priori whether any such defect exists. Thus, one can report fasting insulin simply as a qualitative reflection of insulin resistance. Indices, which also include glucose, appear to add little to the fasting insulin itself. If β‐cell failure progresses, the interpretation of fasting insulin per se becomes impossible. Finally, as of this writing it is not possible to recommend insulin sensitivity measures calculated from the oral glucose tolerance test due to confounds related to differences in gastric emptying, β‐cell function, and glucose effectiveness. Clearly, studies to identify and validate simpler methods to assess insulin action accurately in the intact subject should be continued.