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The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 7 4418-4419
Copyright © 2005 by The Endocrine Society

Letter to the Editor

Letter re: Limited Accuracy of Surrogates of Insulin Resistance during Puberty in Obese and Lean Children at Risk for Altered Glucoregulation

Rajaram J. Karne, Hui Chen, Gail Sullivan and Michael J. Quon

Diabetes Unit, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Maryland 20892

Address correspondence to: Michael J. Quon, M.D., Ph.D., Chief, Diabetes Unit, National Center for Complementary and Alternative Medicine, National Institutes of Health, 10 Center Drive, Building 10, Room 6C-205, Bethesda, Maryland 20892-1632. E-mail: quonm{at}nih.gov.

To the editor:

Brandou et al. (1) report comparisons between the insulin sensitivity index (SIMM) obtained from minimal model analysis of an iv glucose tolerance test and other surrogate indexes in a cross-sectional study of peripubertal children. The authors conclude that surrogates, including quantitative insulin sensitivity check index (QUICKI), have limited accuracy and are not useful for predicting insulin resistance during puberty in children. These conclusions are based on the finding that SIMM does not correlate well with other simple surrogates. Conclusions drawn by Brandou et al. (1) are not supported by their data and are misleading.

The biggest flaw in the study is the absence of a reference standard directly measuring insulin sensitivity (e.g. euglycemic hyperinsulinemic glucose clamp). SIMM is an indirect estimate obtained by fitting iv glucose tolerance test data to a mathematical model. Another problem is that Brandou et al. use a reduced data set (15 blood samples) rather than the full protocol (30 samples). Moreover, SIMM has well-documented errors in estimating insulin sensitivity (2, 3, 4, 5). When compared with glucose clamp (SIClamp), QUICKI has substantially better correlation with SIClamp than SIMM (4, 5). Test characteristics of QUICKI, including coefficient of variation and discriminant ratio, are significantly better than other surrogates and are comparable to those of clamp (6). Finally, changes in QUICKI after therapeutic interventions are significantly correlated with changes in SIClamp (5, 7, 8), whereas changes in SIMM are unrelated (5). A metaanalysis of insulin-resistant subjects demonstrates that QUICKI is the best fasting surrogate index for predicting onset of diabetes (9). Thus, discordance between QUICKI and SIMM likely reflects problems with the minimal model rather than QUICKI. Others find excellent correlations between QUICKI and glucose clamp in normal, obese, and diabetic populations (6, 7, 8, 10, 11). Previous studies of peripubertal children have validated QUICKI against the glucose clamp in populations similar to that studied by Brandou et al. (12, 13).

Brandou et al. (1) inaccurately use the term "accuracy." An "accurate" surrogate reflects the true value of the variable being measured. Brandou et al. examine only correlations. When we evaluated the accuracy of QUICKI to predict insulin sensitivity determined by glucose clamp (14), we found that it is much more accurate than SIMM. In summary, finding that QUICKI and SIMM do not correlate well has been documented previously. However, the conclusion that QUICKI has limited accuracy in peripubertal children is incorrect. If anything, Brandou et al. (1) provide confirmation of the limited utility of the minimal model for assessing insulin sensitivity.

Received March 10, 2005.

References

  1. Brandou F, Brun JF, Mercier J 2005 Limited accuracy of surrogates of insulin resistance during puberty in obese and lean children at risk for altered glucoregulation. J Clin Endocrinol Metab 90:761–767[Abstract/Free Full Text]
  2. Quon MJ, Cochran C, Taylor SI, Eastman RC 1994 Non-insulin-mediated glucose disappearance in subjects with IDDM: discordance between experimental results and minimal model analysis. Diabetes 43:890–896[Abstract]
  3. Cobelli C, Bettini F, Caumo A, Quon MJ 1998 Overestimation of minimal model glucose effectiveness in presence of insulin response is due to undermodeling. Am J Physiol 275:E1031–E1036
  4. Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ 2000 Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 85:2402–2410[Abstract/Free Full Text]
  5. Chen H, Sullivan G, Yue LQ, Katz A, Quon MJ 2003 QUICKI is a useful index of insulin sensitivity in subjects with hypertension. Am J Physiol Endocrinol Metab 284:E804–E812
  6. Mather KJ, Hunt AE, Steinberg HO, Paradisi G, Hook G, Katz A, Quon MJ, Baron AD 2001 Repeatability characteristics of simple indices of insulin resistance: implications for research applications. J Clin Endocrinol Metab 86:5457–5464[Abstract/Free Full Text]
  7. Perseghin G, Caumo A, Mazzaferro V, Pulvirenti A, Piceni Sereni L, Romito R, Lattuada G, Coppa J, Costantino F, Regalia E, Luzi L 2003 Assessment of insulin sensitivity based on a fasting blood sample in men with liver cirrhosis before and after liver transplantation. Transplantation 76:697–702[Medline]
  8. Katsuki A, Sumida Y, Gabazza EC, Murashima S, Urakawa H, Morioka K, Kitagawa N, Tanaka T, Araki-Sasaki R, Hori Y, Nakatani K, Yano Y, Adachi Y 2002 QUICKI is useful for following improvements in insulin sensitivity after therapy in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 87:2906–2908[Abstract/Free Full Text]
  9. Hanley AJ, Williams K, Gonzalez C, D’Agostino Jr RB, Wagenknecht LE, Stern MP, Haffner SM 2003 Prediction of type 2 diabetes using simple measures of insulin resistance: combined results from the San Antonio Heart Study, the Mexico City Diabetes Study, and the Insulin Resistance Atherosclerosis Study. Diabetes 52:463–469[Abstract/Free Full Text]
  10. Rabasa-Lhoret R, Bastard JP, Jan V, Ducluzeau PH, Andreelli F, Guebre F, Bruzeau J, Louche-Pellissier C, MaItrepierre C, Peyrat J, Chagne J, Vidal H, Laville M 2003 Modified quantitative insulin sensitivity check index is better correlated to hyperinsulinemic glucose clamp than other fasting-based index of insulin sensitivity in different insulin-resistant states. J Clin Endocrinol Metab 88:4917–4923[Abstract/Free Full Text]
  11. Yokoyama H, Emoto M, Fujiwara S, Motoyama K, Morioka T, Komatsu M, Tahara H, Shoji T, Okuno Y, Nishizawa Y 2003 Quantitative insulin sensitivity check index and the reciprocal index of homeostasis model assessment in normal range weight and moderately obese type 2 diabetic patients. Diabetes Care 26:2426–2432[Abstract/Free Full Text]
  12. Uwaifo GI, Fallon EM, Chin J, Elberg J, Parikh SJ, Yanovski JA 2002 Indices of insulin action, disposal, and secretion derived from fasting samples and clamps in normal glucose-tolerant black and white children. Diabetes Care 25:2081–2087[Abstract/Free Full Text]
  13. Gungor N, Saad R, Janosky J, Arslanian S 2004 Validation of surrogate estimates of insulin sensitivity and insulin secretion in children and adolescents. J Pediatr 144:47–55[CrossRef][Medline]
  14. Chen H, Sullivan G, Quon MJ, Assessing the predictive accuracy of QUICKI as a surrogate index for insulin sensitivity using a calibration model. Diabetes, in press



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