Measuring β-cell function relative to insulin sensitivity in youth: does the hyperglycemic clamp suffice?

Abstract

To compare β-cell function relative to insulin sensitivity, disposition index (DI), calculated from two clamps (2cDI, insulin sensitivity from the hyperinsulinemic-euglycemic clamp and first-phase insulin from the hyperglycemic clamp) with the DI calculated from the hyperglycemic clamp alone (hcDI). Complete data from hyperglycemic and hyperinsulinemic-euglycemic clamps were available for 330 youth: 73 normal weight, 168 obese with normal glucose tolerance, 57 obese with impaired glucose tolerance, and 32 obese with type 2 diabetes. The correlation between hcDI and 2cDI and Bland-Altman analysis of agreement between the two were examined. Insulin sensitivity and first-phase insulin from hcDI showed a hyperbolic relationship. The hcDI correlated significantly with 2cDI in the groups combined (r = 0.85, P < 0.001) and within each group separately (r ≥ 62, P < 0.001). Similar to 2cDI, hcDI showed a declining pattern of β-cell function across the glucose-tolerance groups. Overall, hcDI values were 27% greater than 2cDI, due to the hyperglycemic versus euglycemic conditions, reflected in a positive bias with Bland-Altman analysis. β-Cell function relative to insulin sensitivity could be accurately evaluated from a single hyperglycemic clamp, obviating the need for two separate clamp experiments, when lessening participant burden and reducing research costs are important considerations.