Assessment Of Clinical Insulin Resistance

A number of techniques that differ in sophistication, complexity, and sensitivity are currently available to assess the degree of insulin resistance in patients (67,68).

The most widely accepted research ''gold standard'' for delineation of insu- -o lin resistance is the euglycemic hyperinsulinemic clamp technique (67,68). In this procedure, exogenous insulin is infused to maintain a constant plasma insulin level above fasting while glucose is infused at varying rates to keep the blood glucose within a fixed range. The amount of infused glucose required to maintain the blood glucose at the target level over time is an index of insulin sensitivity. As described, the more glucose that has to be infused per unit time in order to maintain the fixed glucose level, the more sensitive the patient is to insulin. With

& u this procedure, the insulin-resistant patient requires much less infused glucose to maintain the basal level of blood glucose. The clamp procedure, therefore, provides a measure of insulin-stimulated whole-body glucose disposal (M value). More specifically, combined with calorimetry studies, the whole-body glucose disposal obtained from the clamp can be further divided into both oxidative and nonoxidative components. Nonoxidative glucose disposal essentially represents glycogen deposition, and it is a reduction in this measured parameter that has traditionally defined insulin resistance.

The clamp has a number of limitations, however, primarily related to its complexity and expense. Due to the rapid feedback needed from multiple glucose checks during the procedure, a well-staffed clinical research setting is usually required (67,68), making clamps unrealistic for clinical practice or large population-based studies.

A second method used clinically to assess insulin resistance is the ''frequently sampled intravenous glucose tolerance test'' (FSIVGTT) or the so-called ''minimal model.'' The FSIVGTT is less invasive and more practical than the clamp and can be applied to larger populations (67,68). However, it is less specific and precise. With this procedure, glucose is injected as an intravenous bolus and blood levels of glucose and insulin are assessed frequently from an indwelling catheter over the next several hours. The results reflect glucose disappearance over time and are entered in a mathematical model that generates a value considered an index of insulin sensitivity, termed Si units. This measure of insulin resistance has been shown to correlate well with the euglycemic hyperinsulinemic clamp in nondiabetic subjects, but its accuracy deteriorates in diabetic subjects because the immediate plasma insulin response to the glucose challenge, a major determinant for this analysis, is diminished. This problem has been addressed in diabetic subjects by analysis after administration of exogenous insulin or a secretagogue (i.e., tolbutamide) during the early parts of testing.

The homeostasis model assessment (HOMA) of insulin sensitivity is another procedure that has received interest (69,70). This approach was proposed approximately 10 years ago as a simple, inexpensive alternative to more sophisticated techniques and derives an estimate of insulin sensitivity from the mathematical modeling of fasting plasma glucose and insulin concentrations. Specifically, an estimate of insulin resistance by HOMA score (70) is calculated with the formula:

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