Measuring β-Cell Function Relative to Insulin Sensitivity in Youth:Does the hyperglycemic clamp suffice?

Lindsey Sjaarda, PHD, SoJung Lee, PHD, Hala Tfayli, MD, Fida Bacha, MD, Marnie Bertolet, PHD and Silva Arslanian, MD

Published online before print December 28, 2012, doi: 10.2337/dc12-1508 Diabetes Care December 28, 2012

Abstract

OBJECTIVE 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).

RESEARCH DESIGN AND METHODS Complete data from hyperglycemic and hyperinsulinemic-euglycemic clamps were available for 330 youth, including 73 normal weight (NW), 168 obese with normal glucose tolerance (OB-NGT), 57 obese with impaired glucose tolerance (OB-IGT), and 32 obese with type 2 diabetes (OB-T2DM). The correlation between hcDI and 2cDI and Bland-Altman analysis of agreement between the two were examined.

RESULTS 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.

CONCLUSIONS 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.