Elsevier

Diabetes & Metabolism

Volume 37, Issue 1, February 2011, Pages 72-78
Diabetes & Metabolism

Original article
Measuring insulin sensitivity in youth: How do the different indices compare with the gold-standard method?Comparaison entre différents indices permettant d’estimer la sensibilité à l’insuline chez l’enfant et la méthode de référence du clamp hyperinsulinémique euglycémique

https://doi.org/10.1016/j.diabet.2010.06.008Get rights and content

Abstract

Aim

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 [INS0]) – and the gold-standard method, the hyperinsulinaemic–euglycaemic clamp (HEC) test, in children.

Methods

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/m2/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.

Results

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], SIisOGTT [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 INS0 [r = −0.59, −0.63].

Conclusion

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.

Résumé

But

Étudier chez l’enfant les corrélations entre trois approches différentes de la mesure de la sensibilité à l’insuline (SI) et la méthode de référence du clamp hyperinsulinémique euglycémique (CHE). Les méthodes évaluées ont été : l’hyperglycémie provoquée par voie intraveineuse (HGPIV), les indices dérivés de l’hyperglycémie provoquée par voie orale (HGPO) et les indices à jeun (HOMA-IR, QUICKI et insulinémie à jeun [INS0]).

Méthodes

Vingt enfants (neuf garçons et 11 filles), âgés en moyenne de 9 ± 2 ans, tous normotolérants au glucose et présentant une cote Z moyenne pour l’IMC de 1,5 ± 0,8 ont été inclus dans l’étude. Un CHE (40 mU/m2/min d’insuline), une HGPIV et une HGPO, d’une durée de trois heures chacune, ont été réalisés. La SI a été mesurée au cours du CHE selon les indices de DeFronzo et de Bergman. Les corrélations ont été estimées par le test de corrélation de Spearman.

Résultats

Les deux mesures de SI dérivées du CHE étaient en corrélation étroite (r = 0,85). La SI estimée par HGPIV présentait des corrélations de 0,69 et 0,74 avec les deux mesures du clamp. Des neuf indices dérivés de l’HGPO, les trois qui montraient les meilleures corrélations avec les mesures du clamp étaient : ISI Matsuda (r = 0,63, 0,68), SIisOGTT (r = 0,53, 0,65) et Log sum insulin (r = −0,64, −0,75). Des corrélations similaires avec le CHE ont été trouvées pour les indices à jeun : HOMA-IR (r = −055, −0,56), QUICKI (r = 0,55, 0,57), et INS0 (r = −0,59, −0,63).

Conclusions

Bien que les indices à jeun estimant la SI soient un choix approprié pour les grandes cohortes, les indices dérivés de l’HGPO représentent une option intéressante puisqu’ils apportent des informations cliniques (degré de tolérance au glucose) ainsi que physiologiques (SI).

Introduction

Insulin resistance is the central component of several conditions that are now seen more frequently in young people, including obesity, polycystic ovarian syndrome and diabetes [1], [2]. Furthermore, the results of several large population-based studies suggest that the clustering of CVD risk factors is highest in children and adolescents with the highest degree of insulin resistance [3], [4], [5], making this group most at risk for developing CVD, type 2 diabetes, and premature mortality. These findings provide a rationale for the measurement of IS in youth to identify this high-risk group, to ascertain its associated features and to evaluate interventions aimed at decreasing insulin resistance.

The measurement of IS remains a challenge. The current gold-standard test, the HEC, involves a constant-rate insulin infusion with concomitant, variable glucose infusion to maintain euglycaemia. The HEC is an invasive time- and labour-intensive approach that is not suitable for epidemiological and diagnostic studies [6]. The modified minimal-model FSIVGTT uses a computer-based mathematical model to measure IS after bolus injection of intravenous glucose, followed 20-min later by a bolus intravenous dose of either insulin or tolbutamide [7]. This method, while validated in young people [8], has the same limitations as the HEC in terms of feasibility for epidemiological and clinical purposes. Surrogate measures of IS derived from the OGTT have also been developed, and appear to be well correlated with estimations derived from clamp studies in adults [9], [10], [11], [12], [13], [14], [15], [16], [17]. Little work, however, has so far been done to evaluate the performance of these surrogate measures in youth. Surrogate estimates of IS from fasting values of glucose and insulin have been developed, and are well validated in adult populations [18], [19]. These fasting indices are more readily acceptable to the patient, more cost-effective and easier to use, however validation studies of such surrogate measures in children remain scarce [7], [20].

The objective of the present study was to examine the degree to which three different approaches to measuring IS correlate with the gold-standard HEC in healthy children–namely, the FSIVGTT, indices derived from the OGTT and selected fasting indices (HOMA, QUICKI and fasting insulin]. To our knowledge, this is the first study to examine the criterion validity of each of these three methods against the gold-standard HEC in a healthy paediatric population.

Section snippets

Study population

Children between 6 and 18 years of age, with heights and weights between the 5th and 95th percentiles for age and gender (thus, including normal weight and overweight/obese youth), were eligible for the present study. Children who were known to be pregnant, to have a chronic illness or to have diabetes were excluded. Participants were recruited as a convenience sample. Written informed consent was obtained from all participants and their parents. The study also received ethical approval from

Results

Twenty healthy children were recruited for the present study. The participants’ baseline characteristics are presented in Table 1. The complete spectrum of stages of sexual maturity was represented in this sample. By design, no participant had impaired fasting glucose, impaired glucose tolerance or diabetes. Age, gender and Tanner stage did not appear to predict IS in this small sample. However, children who had higher BMI Z scores had lower IS, as measured by metabolized glucose, after

Conclusion

In a group of children aged 6–13 years, measurement of IS using the FSIVGTT, OGTT and fasting measures were moderately to highly correlated to the gold-standard HEC test. In particular, three indices derived from the OGTT showed the strongest correlations to clamp results–namely, the ISI Matsuda, SIisOGTT and Log sum insulin. Similar findings have been observed in adults, with these indices all correlating strongly (r = 0.57–0.65) to clamp results [16]. While studies in youth have correlated

Conflict of interest statement

No potential conflicts of interest relevant to this article were reported.

Acknowledgements

The present study was funded by the Garrod Association. The authors also wish to thank the participants and their families for their time and involvement in the present research. In addition, we wish to recognize the invaluable participation of Isabelle Vignault (RN) and Annie Tardif (technician) in the clamp studies.

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