title: Predicting glycated hemoglobin levels in the non-diabetic general population: Development and validation of the DIRECT-DETECT prediction model - a DIRECT study.
abstract: OBJECTIVE
  To develop a prediction model that can predict HbA1c levels after six years in the non-diabetic general population, including previously used readily available predictors.
  
  
  METHODS
  Data from 5,762 initially non-diabetic subjects from three population-based cohorts (Hoorn Study, Inter99, KORA S4/F4) were combined to predict HbA1c levels at six year follow-up. Using backward selection, age, BMI, waist circumference, use of anti-hypertensive medication, current smoking and parental history of diabetes remained in sex-specific linear regression models. To minimize overfitting of coefficients, we performed internal validation using bootstrapping techniques. Explained variance, discrimination and calibration were assessed using R2, classification tables (comparing highest/lowest 50% HbA1c levels) and calibration graphs. The model was externally validated in 2,765 non-diabetic subjects of the population-based cohort METSIM.
  
  
  RESULTS
  At baseline, mean HbA1c level was 5.6% (38 mmol/mol). After a mean follow-up of six years, mean HbA1c level was 5.7% (39 mmol/mol). Calibration graphs showed that predicted HbA1c levels were somewhat underestimated in the Inter99 cohort and overestimated in the Hoorn and KORA cohorts, indicating that the model's intercept should be adjusted for each cohort to improve predictions. Sensitivity and specificity (95% CI) were 55.7% (53.9, 57.5) and 56.9% (55.1, 58.7) respectively, for women, and 54.6% (52.7, 56.5) and 54.3% (52.4, 56.2) for men. External validation showed similar performance in the METSIM cohort.
  
  
  CONCLUSIONS
  In the non-diabetic population, our DIRECT-DETECT prediction model, including readily available predictors, has a relatively low explained variance and moderate discriminative performance, but can help to distinguish between future highest and lowest HbA1c levels. Absolute HbA1c values are cohort-dependent.
authors.affiliation: Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Simone P
authors.identifier: http://orcid.org/0000-0003-3627-6925
authors.initials: SP
authors.lastname: Rauh
authors.affiliation: Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Martijn W
authors.initials: MW
authors.lastname: Heymans
authors.affiliation: Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Anitra D M
authors.initials: AD
authors.lastname: Koopman
authors.affiliation: Department of General Practice and the EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Giel
authors.initials: G
authors.lastname: Nijpels
authors.affiliation: Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Coen D
authors.initials: CD
authors.lastname: Stehouwer
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Thorand
authors.affiliation: Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rathmann
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Meisinger
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Tonia
authors.initials: T
authors.lastname: de Las Heras Gala
authors.affiliation: Research Centre for Prevention and Health, Glostrup Hospital, Capital Region of Denmark, Denmark.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Glümer
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.affiliation: Department of Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Henna
authors.initials: H
authors.lastname: Cederberg
authors.affiliation: Department of Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Kuusisto
authors.affiliation: Department of Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
authors.affiliation: Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, United Kingdom.
authors.forename: Ewan R
authors.initials: ER
authors.lastname: Pearson
authors.affiliation: Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skane University Hospital Malmö, Malmö, Sweden.|Department of Public Health and Clinical Medicine, Umea University, Umea, Sweden.|Harvard Chan School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Franks
authors.affiliation: Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Femke
authors.initials: F
authors.lastname: Rutters
authors.affiliation: Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Dekker
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical
chemical_list: D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human