Assessment of Insulin Sensitivity in Man: A Comparison of Minimal Model- and Euglycaemic Clamp-Derived Measures in Health and Heart Failure

Abstract

1. Simplified protocols for the measurement of insulin resistance will facilitate studies of this potentially important variable. 2. Using the euglycaemic clamp as the reference technique, we have assessed the validity of the insulin sensitivity index (inversely related to insulin resistance) obtained using a high-dose (500 mg/kg), unmodified intravenous glucose tolerance test with a 16 point sampling schedule and analysis using the minimal model of glucose disappearance. The two methods were compared in 10 clinically normal subjects and five patients with severe heart failure secondary to coronary heart disease. 3. The insulin sensitivity index of the minimal model was compared with four clamp-derived measures. Correlation coefficients of 0.72-0.92 (P < 0.01-P < 0.001) were obtained between the two methods over a wide range of insulin sensitivity [model values 1.03-14.63 min-1/(pmol/l) x 10(-5)]. Patients with heart failure had the lowest measures of insulin sensitivity. 4. The high-dose, unmodified intravenous glucose tolerance test with minimal model analysis is a straightforward and economical clinical procedure and provides a valid measure of insulin sensitivity, in health and disease.

Insulin Sensitivity Assessed by Stable Isotopes with Oral Glucose Administration: Validation with Euglycaemic Clamp

“…However, it is of some concern that the two methods are apparently not measuring the same metabolic parameter, since the intercept of the plot, Figure 2, is clearly not equal to zero. This parallels closely the situation for the IVGTT itself, which has been compared with clamps on a number of occasions [3, 7, 28–31]. A significant relationship between the IVGTT and clamp was not achieved in an early study with a very homogenous population [29], but was later demonstrated when wider spectrums of insulin sensitivity were investigated [3, 7].…”

Abnormalities of whole body protein turnover, muscle metabolism and levels of metabolic hormones in patients with chronic heart failure

“…Both impaired skeletal muscle glucose uptake and impaired insulin‐mediated inhibition of endogenous glucose production has been demonstrated using the glucose clamp technique [23]. This has been confirmed in larger studies using a minimal model approach and an intravenous glucose tolerance test [24, 25]. The molecular mechanisms underlying skeletal muscle insulin resistance are not fully understood [7, 26, 27].…”

Maximizing the success rate of minimal model insulin sensitivity measurement in humans: the importance of basal glucose levels

“…This sample comprised five groups of 20 IVGTTs from studies of apparently healthy pre-and post-menopausal women (groups 1 and 2) [16,17], apparently healthy men (group 3), and men with coronary heart disease (group 4) or chronic heart failure (group 5) [18]. Insulin sensitivity estimates derived using this protocol have been shown to correlate well with those from the euglycaemic hyperinsulinaemic clamp, and to behave as expected in situations in which variation in insulin sensitivity has been previously well characterized [8,19]. The first 20 consecutive IVGTTs by date-of-test in each group were selected for inclusion in the present analysis.…”

“…In a previously published study [8], 15 volunteers (10 apparently healthy men and women and five patients with chronic heart failure) each underwent a euglycaemic hyperinsulinaemic clamp and an IVGTT according to the protocol described above. In the present study, the IVGTT data were re-analysed according to the four most successful implementation procedures, and the values for S I obtained were correlated with a clamp-derived measure of insulin sensitivity.…”