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Development of a Type 2 Diabetes Risk Model From a Panel of Serum Biomarkers From the Inter99 Cohort
- Kolberg, Janice A., Jørgensen, Torben, Gerwien, Robert W., Hamren, Sarah, McKenna, Michael P., Moler, Edward, Rowe, Michael W., Urdea, Mickey S., Xu, Xiaomei M., Hansen, Torben, Pedersen, Oluf, Borch-Johnsen, Knut
- Diabetes care 2009 v.32 no.7 pp. 1207-1212
- C-reactive protein, adiponectin, biomarkers, blood glucose, blood serum, body mass index, fasting, ferritin, glucose, immunoassays, insulin, interleukin-2, learning, model validation, models, noninsulin-dependent diabetes mellitus, risk, waist circumference
- 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 greater-than-or-equal39 years, with BMI greater-than-or-equal25 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.