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*, Martijn W. Heymans, Anitra D. M. Koopman, Giel Nijpels, Coen D. Stehouwer, Barbara Thorand, Wolfgang Rathmann, Christa Meisinger, Annette Peters, Tonia de las Heras Gala, Charlotte Glumer, Oluf Pedersen, Henna Cederberg, Johanna Kuusisto, Markku Laakso, Ewan R. Pearson, Paul W. Franks, Femke Rutters, Jacqueline M. Dekker

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Web of Science)

Abstract

Aims/hypothesis

To develop a prediction model that can predict HbA1 c 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 54/F4) were combined to predict HbAl c 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 R-2, classification tables (comparing highest/lowest 50% HbA1 c 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 HbAlc level was 5.6% (38 mmol/mol). After a mean follow-up of six years, mean HbAlc 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.

Original languageEnglish
Article number0171816
Number of pages13
JournalPLOS ONE
Volume12
Issue number2
DOIs
Publication statusPublished - 10 Feb 2017

Keywords

  • TYPE-2 DIABETES RISK
  • HISPANIC WHITE ADULTS
  • KORA S4/F4 COHORT
  • LIFE-STYLE
  • INSULIN SENSITIVITY
  • CAUCASIAN POPULATION
  • GLUCOSE-TOLERANCE
  • FOLLOW-UP
  • METAANALYSIS
  • MELLITUS

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