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. 2017 Feb 10;12(2):e0171816.
doi: 10.1371/journal.pone.0171816. eCollection 2017.

Predicting glycated hemoglobin levels in the non-diabetic general population: Development and validation of the DIRECT-DETECT prediction model - a DIRECT study

Simone P Rauh  1 , Martijn W Heymans  1 , Anitra D M Koopman  1 , Giel Nijpels  2 , Coen D Stehouwer  3 , Barbara Thorand  4   5 , Wolfgang Rathmann  6 , Christa Meisinger  4 , Annette Peters  4   5 , Tonia de Las Heras Gala  4 , Charlotte Glümer  7 , Oluf Pedersen  8 , Henna Cederberg  9 , Johanna Kuusisto  9 , Markku Laakso  9 , Ewan R Pearson  10 , Paul W Franks  11   12   13 , Femke Rutters  1 , Jacqueline M Dekker  1
Affiliations

Predicting glycated hemoglobin levels in the non-diabetic general population: Development and validation of the DIRECT-DETECT prediction model - a DIRECT study

Simone P Rauh et al. PLoS One. .

Abstract

Aims/hypothesis: 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/interpretation: 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.

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Conflict of interest statement

The Novo Nordisk funding did not influence the scientific work, or have any influence on design, data collection, analyses or interpretation of the results. We can confirm that this does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Calibration graphs (in deciles) of the prediction model after internal validation.
(A) For men, in the development dataset (The Hoorn Study, The KORA S4/F4 Study and the Inter99 Study combined). (B) For men, in the development dataset, stratified per cohort: Hoorn Study (dots), KORA F4/S4 Study (squares), Inter99 Study (triangles). (C) For women, in the development dataset (The Hoorn Study, The KORA S4/F4 Study and the Inter99 Study combined). (D) For women, in the development dataset, stratified per cohort: Hoorn Study (dots), KORA F4/S4 Study (squares), Inter99 Study (triangles). (E) For men, in the external validation dataset (The METSIM Study). The diagonal line indicates perfect calibration.
See this image and copyright information in PMC

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