The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 7 4419
Copyright © 2005 by The Endocrine Society
Authors’ Response: Limited Accuracy of Surrogates of Insulin Resistance during Puberty in Obese and Lean Children at Risk for Altered Glucoregulation
F. Brandou,
J. F. Brun,
E. Raynaud and
J. Mercier
Equipe d’Acceuil EA 701 Physiologie des Interactions, Service Central de Physiologie Clinique, Centre d’Exploration et de Réadaptation des Anomalies du Métabolisme Musculaire (CERAMM), Centre Hospitalier Universitaire Lapeyronie, 34295 Montpellier Cedex 5, France
Address correspondence to: J. F. Brun, Centre d’Exploration et de Réadaptation des Anomalies du Métabolisme Musculaire (CERAMM), Centre Hospitalier Universitaire Lapeyronie, 34295 Montpellier Cedex 5, France. E-mail: drjfbrun{at}dixinet.com.
To the editor:
In response to the comments of Karne et al. (1), the purpose of our study (2) was not to demonstrate that quantitative insulin sensitivity check index (QUICKI) and other surrogates of insulin sensitivity (SI) are meaningless. On the contrary, we have reported their accuracy in adults (3) and proposed a simplified version (SI = 40/Ib) (4).
However, no biological method is above criticism—even the glucose clamp has some methodological limits (5, 6). Actually, none of those methods cited by Karne et al. (1) for the minimal model (MM) has been recognized as a major flaw, and a huge body of literature demonstrates the robustness of this approach (7, 8). The concerns about glucose effectiveness have no influence on SI calculations (9). Our reduced sampling procedure has been validated (10). No serious scientist would easily believe that the MM (which has been extensively investigated and used in studies published in leading journals over the past 25 yr) provides a less accurate measurement than simple indexes based on baseline values.
Despite the statement of Karne et al. (1), SI-MM usually correlates as closely as SI-clamp with all surrogates in adults (11, 12). However, this correlation disappears in certain populations. We do not understand why Karne et al. so angrily dispute the fact, which is evidenced by many investigators (13, 14), that surrogates (including QUICKI) have limits to their validity, as is the case for any physiological model.
It is clear that during puberty insulinemia mirrors SI less closely. It is not appropriate to conclude that our findings are false only because Uwaifo et al. (15) have found a correlation in prepubertal children between QUICKI and SI, as others found in healthy pubertal children (16). Those reports do not mean that similar correlations are to be found in pubertal children at risk of disturbed glucoregulation, in whom the feedback loop between SI and insulinemia is even more disturbed.
QUICKI and homeostasis model assessment can safely be used as predictors of SI in lean and obese sedentary individuals, but in other populations (e.g. diabetics, athletes, individuals with high SI, puberty, etc.), serious concerns have been raised about their use that argue for caution. Our hope is that further study will extend the range of populations in which surrogates can be employed. However, to deny the relevance of studies that point out their limits of validity is probably not the best way to reach this goal. The potential consequences of such a "rigid" position may unfortunately be that surrogates will lose much of their credibility in the near future. Our purpose in this study was just the opposite.
Received March 23, 2005.
References
- Karne RJ, Chen H, Sullivan G, Quon MJ 2005 Letter re: Limited accuracy of surrogates of insulin resistance during puberty in obese and lean children at risk for altered glucoregulation. J Clin Endocrinol Metab 90:4418–4419[Free Full Text]
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