title: Modeling glucose and free fatty acid kinetics in glucose and meal tolerance test.
abstract: BACKGROUND
  Quantitative evaluation of insulin regulation on plasma glucose and free fatty acid (FFA) in response to external glucose challenge is clinically important to assess the development of insulin resistance (World J Diabetes 1:36-47, 2010). Mathematical minimal models (MMs) based on insulin modified frequently-sampled intravenous glucose tolerance tests (IM-FSIGT) are widely applied to ascertain an insulin sensitivity index (IEEE Rev Biomed Eng 2:54-96, 2009). Furthermore, it is important to investigate insulin regulation on glucose and FFA in postprandial state as a normal physiological condition. A simple way to calculate the appearance rate (Ra) of glucose and FFA would be especially helpful to evaluate glucose and FFA kinetics for clinical applications.
  
  
  METHODS
  A new MM is developed to simulate the insulin modulation of plasma glucose and FFA, combining IM-FSIGT with a mixed meal tolerance test (MT). A novel simple functional form for the appearance rate (Ra) of glucose or FFA in the MT is developed. Model results are compared with two other models for data obtained from 28 non-diabetic women (13 African American, 15 white).
  
  
  RESULTS
  The new functional form for Ra of glucose is an acceptable empirical approximation to the experimental Ra for a subset of individuals. When both glucose and FFA are included in FSIGT and MT, the new model is preferred using the Bayes Information Criterion (BIC).
  
  
  CONCLUSIONS
  Model simulations show that the new MM allows consistent application to both IM-FSIGT and MT data, balancing model complexity and data fitting. While the appearance of glucose in the circulation has an important effect on FFA kinetics in MT, the rate of appearance of FFA can be neglected for the time-period modeled.
authors.affiliation: Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), MSC 5621, LBM, NIDDK, NIH, Bethesda, MD, 20892-5621, USA. liy16@mail.nih.gov.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), MSC 5621, LBM, NIDDK, NIH, Bethesda, MD, 20892-5621, USA. carsonc@niddk.nih.gov.
authors.forename: Carson C
authors.initials: CC
authors.lastname: Chow
authors.affiliation: Nutrition Department, Clinical Center, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD, 20892, USA. courvillea@mail.nih.gov.
authors.forename: Amber B
authors.initials: AB
authors.lastname: Courville
authors.affiliation: Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD, 20892, USA. annes@intra.niddk.nih.gov.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Sumner
authors.affiliation: Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), MSC 5621, LBM, NIDDK, NIH, Bethesda, MD, 20892-5621, USA. vipulp@mail.nih.gov.
authors.forename: Vipul
authors.initials: V
authors.lastname: Periwal
mesh_terms: D000328:Adult; D001741:Black or African American; D000465:Algorithms; D001499:Bayes Theorem; D001786:Blood Glucose / Q000032:analysis*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D005502:Food; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D008962:Models, Theoretical; D014481:United States
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D005947:Glucose