Development of a type 2 diabetes risk model from a panel of serum biomarkers from the Inter99 cohort.
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.


METHODS
Subjects were selected from the Inter99 cohort, a longitudinal population-based study of approximately 6,600 Danes in a nested case-control design with the primary outcome of 5-year conversion to type 2 diabetes. Nondiabetic subjects, aged >or=39 years, with BMI >or=25 kg/m(2) 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.
Kolberg
Janice A
JA
Tethys Bioscience, Emeryville, California, USA. jkolberg@tethysbio.com
Jørgensen
Torben
T
Gerwien
Robert W
RW
Hamren
Sarah
S
McKenna
Michael P
MP
Moler
Edward
E
Rowe
Michael W
MW
Urdea
Mickey S
MS
Xu
Xiaomei M
XM
Hansen
Torben
T
Pedersen
Oluf
O
Borch-Johnsen
Knut
K
D052242:Adiponectin / Q000097:blood; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology*; D005260:Female; D005293:Ferritins / Q000097:blood; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007118:Immunoassay; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors
D052242:Adiponectin; D015415:Biomarkers; D001786:Blood Glucose; D002097:C-Reactive Protein; D005293:Ferritins; D006442:Glycated Hemoglobin; D007328:Insulin; D015375:Receptors, Interleukin-2