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DDMODEL00000005: Lledo-Garcia_2013_diabetes

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A semi-mechanistic model of the relationship between average glucose and HbA1c in healthy and diabetic subjects. Lledó-García R, Mazer NA, Karlsson MO, IGRH model Journal of pharmacokinetics and pharmacodynamics, 4/2013, Volume 40, Issue 2, pages: 129-142
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  • A semi-mechanistic model of the relationship between average glucose and HbA1c in healthy and diabetic subjects.
  • Lledó-García R, Mazer NA, Karlsson MO
  • Journal of pharmacokinetics and pharmacodynamics, 4/2013, Volume 40, Issue 2, pages: 129-142
  • Pharmacometrics Research Group, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, SE 751 24, Uppsala, Sweden. rocio.lledo@gmail.com
  • HbA1c is the most commonly used biomarker for the adequacy of glycemic management in diabetic patients and a surrogate endpoint for anti-diabetic drug approval. In spite of an empirical description for the relationship between average glucose (AG) and HbA1c concentrations, obtained from the A1c-derived average glucose (ADAG) study by Nathan et al., a model for the non-steady-state relationship is still lacking. Using data from the ADAG study, we here develop such models that utilize literature information on (patho)physiological processes and assay characteristics. The model incorporates the red blood cell (RBC) aging description, and uses prior values of the glycosylation rate constant (KG), mean RBC life-span (LS) and mean RBC precursor LS obtained from the literature. Different hypothesis were tested to explain the observed non-proportional relationship between AG and HbA1c. Both an inverse dependence of LS on AG and a non-specificity of the National Glycohemoglobin Standardization Program assay used could well describe the data. Both explanations have mechanistic support and could be incorporated, alone or in combination, in models allowing prediction of the time-course of HbA1c changes associated with changes in AG from, for example dietary or therapeutic interventions, and vice versa, to infer changes in AG from observed changes in HbA1c. The selection between the alternative mechanistic models require gathering of new information.
Paolo Magni
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  • Model owner: Paolo Magni
  • Submitted: Sep 26, 2014 3:32:40 PM
  • Last Modified: Oct 10, 2016 9:42:06 PM
Revisions
  • Version: 12 public model Download this version
    • Submitted on: Oct 10, 2016 9:42:06 PM
    • Submitted by: Paolo Magni
    • With comment: Update MDL syntax to the version 1.0 and R script to SEE version 2.0.0. Code automatically generated for NONMEM and MONOLIX
  • Version: 11 public model Download this version
    • Submitted on: Jun 2, 2016 8:27:17 PM
    • Submitted by: Paolo Magni
    • With comment: Model revised without commit message
  • Version: 10 public model Download this version
    • Submitted on: Jun 2, 2016 8:24:02 PM
    • Submitted by: Paolo Magni
    • With comment: Updated model annotations.
  • Version: 7 public model Download this version
    • Submitted on: Dec 11, 2015 12:36:07 PM
    • Submitted by: Paolo Magni
    • With comment: Edited model metadata online.
  • Version: 3 public model Download this version
    • Submitted on: Sep 26, 2014 3:32:40 PM
    • Submitted by: Paolo Magni
    • With comment: Model revised without commit message
 
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