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The BIGTT Test

A novel test for simultaneous measurement of pancreatic β-cell function, insulin sensitivity, and glucose tolerance

  1. Torben Hansen, MD, PHD1,
  2. Thomas Drivsholm, MD, PHD2,
  3. Søren A. Urhammer, MD, DMSCI1,
  4. Rene T. Palacios, MSCI3,
  5. Aage Vølund, MSCI3,
  6. Knut Borch-Johnsen, MD, DMSCI12 and
  7. Oluf Pedersen, MD, DMSCI1
  1. 1Steno Diabetes Center, Copenhagen, Denmark
  2. 2Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
  3. 3Department of Biostatistics, Novo Nordisk, Copenhagen, Denmark
  1. Address correspondence and reprint requests to Torben Hansen, MD, PhD, Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark. E-mail: toha{at}steno.dk

Abstract

OBJECTIVE—Insulin resistance and impaired β-cell function are key elements in the pathogenesis of type 2 diabetes. We aimed to develop valid algorithms for estimation of the insulin sensitivity index (SI) and acute insulin response (AIR) derived from simple and cheap physiological measurements that could be used in large-scale metabolic, genetic, and epidemiological studies.

RESEARCH DESIGN AND METHODS—For our purpose, data from an oral glucose tolerance test (OGTT) (18 samples during 240 min) and a tolbutamide-modified intravenous glucose tolerance test (IVGTT) (33 samples during 180 min) from 258 individuals with fasting plasma glucose <7 mmol/l and 2-h plasma glucose <7.8 mmol/l were used for model development and internal validation. Data from an additional 28 individuals were used for external validation. Bergman’s minimal model was used to calculate SI, and the trapezoidal method was used to calculate AIR0–8 min. Multiple linear regression was applied to derive predictive equations of log(SI) and log(AIR0–8 min) using data on sex, BMI, plasma glucose, and serum insulin levels obtained during the OGTT.

RESULTS—We demonstrate that it is possible to obtain estimates of SI (BIGTT-SI) and AIR (BIGTT-AIR) that are highly correlated to IVGTT-derived values of SI (R2 = 0.77) and AIR (R2 = 0.54). In the two validation datasets we obtained similar results.

CONCLUSIONS—Data from OGTTs can provide accurate measures of insulin sensitivity and β-cell function, which can be used in large scale metabolic, genetic, and epidemiological studies.

Footnotes

  • T.H. and T.D. contributed equally to this work.

    Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/dc06-1240.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    • Accepted October 19, 2006.
    • Received June 15, 2006.
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