Presentation of a New Method for Specific Measurement of in Vivo Insulin-Stimulated Glucose Disposal in Humans: Comparison of This Approach with the Insulin Clamp and Minimal Model Techniques*

Abstract

This study was initiated to compare the abilities of two alternative approaches to the measurement of insulin-dependent glucose disposal in normal humans. The ability of insulin to stimulate glucose disposal was measured in 12 normal subjects by determining glucose disposal rates during insulin clamp studies carried out at both basal insulin concentrations (approximately 6 microU/ml) and during a period of sustained hyperinsulinemia (approximately 60 microU/ml). The increment in glucose disposal was defined as insulin-dependent disposal and compared to estimates of insulin action generated by both the conventional insulin clamp approach and the minimal model technique. The results documented an extremely close correlation (r = 0.99; P less than 0.001) between the direct determination of insulin-dependent glucose disposal and insulin-stimulated glucose disposal as estimated by the insulin clamp technique. In contrast, there was a poor correlation (r = 0.44; P = NS) between insulin sensitivity as estimated by the minimal model technique and insulin-dependent glucose disposal. These results indicate that the value of glucose disposal determined by the insulin clamp approach, which includes both insulin-independent and insulin-dependent glucose disposal, provides an excellent estimate of insulin-dependent glucose disposal in subjects with normal glucose tolerance. Unfortunately, this does not appear to be true of the minimal model technique. However, it must be emphasized that these conclusions are only applicable to normal humans, and may not apply to normal subjects of other species or to humans under different physiological or pathological situations.

Assessment of Insulin Sensitivity from Measurements in the Fasting State and during an Oral Glucose Tolerance Test in Polycystic Ovary Syndrome and Menopausal Patients

“…In conclusion, our data show that several indirect indexes of insulin resistance obtained from fasting or stimulated glucose, insulin, or C-peptide concentrations are superimposable, in terms of strength of association with the clamp data, to those reported by other researchers for the minimal model (25,35,36), suggesting that they can effectively replace the minimal model or clamp evaluations in large population studies, in particular those involving PCOS or menopausal women. The presence of a high correlation coefficient does not mean that these indexes have the best predictive performance in diagnosing insulin resistance, because of the presence of many borderline values.…”

“…Furthermore, there is not general agreement about the levels of correlation obtained between direct measures of insulin sensitivity (i.e. glucose clamp) and indirect measures, such as minimal model analysis, with correlation coefficients varying from 0.44 -0.90 (25,35,36).…”

QUICKI is a useful index of insulin sensitivity in subjects with hypertension

“…The authors of that study claim that errors in their minimal-model approach are constant and therefore unbiased with respect to determining changes in insulin sensitivity (12). However, this is clearly not the case, since the SI MM from the unmodified FSIVGTT that they used (without insulin infusion) does not significantly correlate with SI Clamp (10). As illustrated in the present study, one may observe a poor correlation between QUICKI and SI MM while still maintaining an excellent correlation between QUICKI and the reference glucose clamp results.…”

“…Typcially used insulin doses in the literature range between 0.02 and 0.05 U/kg. Blood samples were collected for blood glucose and plasma insulin determinations at Ϫ10, Ϫ1, 1, 2, 3, 4, 5, 6,7,8,10,12,14,16,20,22,23,24,25,27,30,40,50, 60, 70, 80, 90, 100, 120, 160, and 180 min, as described (34). Data were subjected to minimal-model analysis using the computer program MINMOD (generous gift from R. N. Bergman) to generate predictions of glucose disappearance and insulin sensitivity (SI MM) (4).…”

Effect of Glipizide Treatment on Response to an Infused Glucose Load in Patients With NIDDM

“…A second level of uncertainty relates to whether the enhanced ability of an individual to respond to a glucose challenge associated with sulfonylurea treatment can be seen at basal insulin levels, in response to physiological hyperinsulinemia, and whether or not there is any effect of the incremental increase in insulin concentration on glucose homeostasis. This distinction is often overlooked because of the widespread use of the hyperinsulinemic clamp to assess glucose disposal, a method that measures total glucose uptake, i.e., basal plus glucose uptake in response to an increase in insulin concentration (7,8). Thus, irrespective of whether the increase in peripheral glucose disposal associated with sulfonylurea represents a direct effect or one that is secondary to a decrease in glucose toxicity, we do not know the relative importance of changes in glucose disposal rate that occur in response to varying insulin concentrations.…”