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Letters: Comments and Responses

Diagnosing Insulin Resistance by Simple Quantitative Methods in Subjects With Normal Glucose Metabolism

Response to Ascaso et al.

  1. Rajaram J. Karne, MD,
  2. Hui Chen, MD and
  3. Michael J. Quon, MD, PHD
  1. From the Diabetes Unit, National Center for Complementary and Alternative Medicine (NCCAM), National Institutes of Health, Bethesda, Maryland
  1. Address correspondence to Michael J. Quon, MD, PhD, Chief, Diabetes Unit, NCCAM, NIH, 10 Center Dr., Building 10, Room 6C-205, Bethesda, MD 20892-1632. E-mail: quonm{at}nih.gov
Diabetes Care 2004 May; 27(5): 1247-1248. https://doi.org/10.2337/diacare.27.5.1247-a
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Response to Ascaso et al.

Ascaso et al. (1) evaluated insulin sensitivity in 65 healthy subjects using minimal model analysis of an insulin-modified frequently sampled intravenous glucose tolerance test (FSIVGTT) to estimate the insulin sensitivity parameter derived from minimal model (SIMM) (2), as well as simple surrogates including fasting insulin, homeostasis model assessment (3), QUICKI (4), and the McAuley index (5). A statistically significant correlation was observed between SIMM and all of the other surrogate indexes examined. However, using SIMM as the reference method, the authors claim that the McAuley index has the best correlation with SIMM and the highest sensitivity and specificity (0.75 and 0.91, respectively). Therefore, the authors conclude that among several simple surrogate indexes, the McAuley index is the most sensitive and specific measure of insulin sensitivity.

While the data presented by Ascaso et al. may be sound, the conclusions drawn are not supported by the data. The main problem with the interpretation of the data comes from not including a true reference standard that is a direct measure of insulin sensitivity (e.g., euglycemic-hyperinsulinemic glucose clamp). SIMM derived from an FSIVGTT is not a direct measure of insulin sensitivity. Moreover, SIMM has well-documented systematic and random errors that are problematic even when insulin-modified FSIVGTTs are used (4,6–9). When compared with glucose clamp–derived measurements of insulin sensitivity (SIClamp), QUICKI is a substantially and significantly better estimate of insulin sensitivity than SIMM (4). Moreover, in hypertensive subjects, changes in QUICKI after therapeutic intervention are significantly correlated with changes in SIClamp, while changes in SIMM are unrelated (9). Thus, discordance between QUICKI and SIMM most likely reflects problems associated with the minimal model approach rather than inaccuracies manifested by QUICKI. Indeed, a number of independent groups have found excellent correlations between QUICKI and reference glucose clamp measurements in normal, obese, and diabetic populations (10–16), as well as in pregnant women and women with gestational diabetes (17). Because Ascaso et al. used SIMM as their reference method and they do not include a direct measure of insulin sensitivity in their analysis, it is problematic to make sound conclusions regarding the relative merits of various surrogate indexes for insulin sensitivity. An additional problem with the analysis presented by Ascaso et al. is that they do not use statistical methods to compare the differences in sensitivity and specificity among the various indexes. For example, it is uncertain whether the sensitivity and specificity of the McAuley index (0.75 and 0.91, respectively) are significantly better than that reported for QUICKI (0.65 and 0.87, respectively). In summary, when evaluating the relative merits of simple surrogate measures for insulin sensitivity, it is important to include a direct measurement of insulin sensitivity as a reference standard and to use appropriate statistical analysis so that valid conclusions may be made.

Footnotes

  • DIABETES CARE

References

  1. ↵
    Ascaso JF, Pardo S, Real JT, Lorente RI, Priego A, Carmena R: Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism. Diabetes Care 26:3320–3325, 2003
    OpenUrlAbstract/FREE Full Text
  2. ↵
    Finegood DT, Hramiak IM, Dupre J: A modified protocol for estimation of insulin sensitivity with the minimal model of glucose kinetics in patients with insulin-dependent diabetes. J Clin Endocrinol Metab 70:1538–1549, 1990
    OpenUrlCrossRefPubMedWeb of Science
  3. ↵
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419, 1985
    OpenUrlCrossRefPubMedWeb of Science
  4. ↵
    Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ: Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 85:2402–2410, 2000
    OpenUrlCrossRefPubMedWeb of Science
  5. ↵
    McAuley KA, Williams SM, Mann JI, Walker RJ, Lewis-Barned NJ, Temple LA, Duncan AW: Diagnosing insulin resistance in the general population. Diabetes Care 24:460–464, 2001
    OpenUrlAbstract/FREE Full Text
  6. ↵
    Quon MJ, Cochran C, Taylor SI, Eastman RC: Non–insulin-mediated glucose disappearance in subjects with IDDM: discordance between experimental results and minimal model analysis. Diabetes 43:890–896, 1994
    OpenUrlAbstract/FREE Full Text
  7. Finegood DT, Tzur D: Reduced glucose effectiveness associated with reduced insulin release: an artifact of the minimal-model method. Am J Physiol 271:E485–E495, 1996
    OpenUrlPubMedWeb of Science
  8. Cobelli C, Bettini F, Caumo A, Quon MJ: Overestimation of minimal model glucose effectiveness in presence of insulin response is due to undermodeling. Am J Physiol 275:E1031–E1036, 1998
    OpenUrlPubMed
  9. ↵
    Chen H, Sullivan G, Yue LQ, Katz A, Quon MJ: QUICKI is a useful index of insulin sensitivity in subjects with hypertension. Am J Physiol Endocrinol Metab 284:E804–E812, 2003
    OpenUrlAbstract/FREE Full Text
  10. ↵
    Mather KJ, Hunt AE, Steinberg HO, Paradisi G, Hook G, Katz A, Quon MJ, Baron AD: Repeatability characteristics of simple indices of insulin resistance: implications for research applications. J Clin Endocrinol Metab 86:5457–5464, 2001
    OpenUrlCrossRefPubMedWeb of Science
  11. Bastard JP, Robert JJ, Jardel C, Bruckert E, Grimaldi A, Hainque B: Is quantitative insulin sensitivity check index a fair insulin sensitivity index in humans? Diabetes Metab 27:69–70, 2001
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  12. 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: 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, 2003
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  13. Yokoyama H, Emoto M, Fujiwara S, Motoyama K, Morioka T, Komatsu M, Tahara H, Shoji T, Okuno Y, Nishizawa Y: 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, 2003
    OpenUrlAbstract/FREE Full Text
  14. 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: 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, 2002
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  15. Uwaifo GI, Fallon EM, Chin J, Elberg J, Parikh SJ, Yanovski JA: 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, 2002
    OpenUrlAbstract/FREE Full Text
  16. ↵
    Perseghin G, Caumo A, Mazzaferro V, Pulvirenti A, Piceni Sereni L, Romito R, Lattuada G, Coppa J, Costantino F, Regalia E, Luzi L: Assessment of insulin sensitivity based on a fasting blood sample in men with liver cirrhosis before and after liver transplantation. Transplantation 76:697–702, 2003
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    Kirwan JP, Huston-Presley L, Kalhan SC, Catalano PM: Clinically useful estimates of insulin sensitivity during pregnancy: validation studies in women with normal glucose tolerance and gestational diabetes mellitus. Diabetes Care 24:1602–1607, 2001
    OpenUrlAbstract/FREE Full Text
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Diagnosing Insulin Resistance by Simple Quantitative Methods in Subjects With Normal Glucose Metabolism
Rajaram J. Karne, Hui Chen, Michael J. Quon
Diabetes Care May 2004, 27 (5) 1247-1248; DOI: 10.2337/diacare.27.5.1247-a

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Diagnosing Insulin Resistance by Simple Quantitative Methods in Subjects With Normal Glucose Metabolism
Rajaram J. Karne, Hui Chen, Michael J. Quon
Diabetes Care May 2004, 27 (5) 1247-1248; DOI: 10.2337/diacare.27.5.1247-a
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