Measuring insulin sensitivity in youth: How do the different indices compare with the gold-standard method?

The objective of the study was to examine the correlation between three methods of measuring insulin sensitivity (IS) - namely, the frequently sampled intravenous glucose tolerance test (FSIVGTT), indices derived from the oral glucose tolerance test (OGTT) and fasting indices (HOMA-IR, QUICKI, fasting insulin [INS(0)]) - and the gold-standard method, the hyperinsulinaemic-euglycaemic clamp (HEC) test, in children.

A total of 20 children [nine boys and 11 girls; mean (SD) age: 9 (2) years] were studied. Their mean (SD) BMI Z score was 1.5 (0.8). All participants had normal glucose metabolism. Each child underwent a 3-h HEC (40 mU/m(2)/min of insulin), an insulin-modified minimal-model FSIVGTT and a 3-h OGTT. The clamp-derived IS was calculated, using DeFronzo's metabolized glucose index and Bergman's IS index. Correlations were established using Spearman's rank correlations.

The two clamp-derived measures were highly correlated (r=0.85), and the IS measured from the FSIVGTT was well correlated with both clamp measures [r=0.69, 0.74]. Of the nine indices derived from the OGTT, the three with the highest correlation with clamp results were the ISI Matsuda [r=0.63, 0.68], SI(is)OGTT [r=0.53, 0.65] and log sum insulin [r=-0.64, -0.75]. Fasting indices of IS had similar correlations to clamp results: HOMA-IR [r=-0.55, -0.56]; QUICKI [r=0.55, 0.57]; and INS(0) [r=-0.59, -0.63].

While fasting-based indices of IS are a suitable option for large cohorts, OGTT-derived indices may represent a useful compromise for obtaining both clinical (glucose tolerance) and physiological (insulin sensitivity) information, making them particularly useful for large-scale physiological and epidemiological studies.