Development of a Type 2 Diabetes Risk Model From a Panel of Serum Biomarkers From the Inter99 Cohort
- Janice A. Kolberg, PHD1,
- Torben Jørgensen, MD, DMSC2,3,
- Robert W. Gerwien, PHD1,
- Sarah Hamren, BS1,
- Michael P. McKenna, PHD1,
- Edward Moler, PHD1,
- Michael W. Rowe, PHD1,
- Mickey S. Urdea, PHD1,
- Xiaomei M. Xu, MS1,
- Torben Hansen, MD, PHD4,
- Oluf Pedersen, MD, DMSC3,4,5 and
- Knut Borch-Johnsen, MD, DMSC4,5
- 1Tethys Bioscience, Emeryville, California;
- 2Research Centre for Prevention and Health, Glostrup Hospital, Copenhagen, Denmark;
- 3Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark;
- 4Steno Diabetes Center, Copenhagen, Denmark;
- 5Faculty of Health Science, University of Aarhus, Aarhus, Denmark.
- Corresponding author: Janice A. Kolberg, jkolberg{at}tethysbio.com.
Abstract
OBJECTIVE The purpose of this study was to develop a model for assessing the 5-year risk of developing type 2 diabetes from a panel of 64 circulating candidate biomarkers.
RESEARCH DESIGN AND METHODS Subjects were selected from the Inter99 cohort, a longitudinal population-based study of ∼6,600 Danes in a nested case-control design with the primary outcome of 5-year conversion to type 2 diabetes. Nondiabetic subjects, aged ≥39 years, with BMI ≥25 kg/m2 at baseline were selected. Baseline fasting serum samples from 160 individuals who developed type 2 diabetes and from 472 who did not were tested. An ultrasensitive immunoassay was used to measure of 58 candidate biomarkers in multiple diabetes-associated pathways, along with six routine clinical variables. Statistical learning methods and permutation testing were used to select the most informative biomarkers. Risk model performance was estimated using a validated bootstrap bias-correction procedure.
RESULTS A model using six biomarkers (adiponectin, C-reactive protein, ferritin, interleukin-2 receptor A, glucose, and insulin) was developed for assessing an individual's 5-year risk of developing type 2 diabetes. This model has a bootstrap-estimated area under the curve of 0.76, which is greater than that for A1C, fasting plasma glucose, fasting serum insulin, BMI, sex-adjusted waist circumference, a model using fasting glucose and insulin, and a noninvasive clinical model.
CONCLUSIONS A model incorporating six circulating biomarkers provides an objective and quantitative estimate of the 5-year risk of developing type 2 diabetes, performs better than single risk indicators and a noninvasive clinical model, and provides better stratification than fasting plasma glucose alone.
Footnotes
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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.
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- Received October 25, 2008.
- Accepted February 21, 2009.
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Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
- © 2009 by the American Diabetes Association.
