Abstract

BackgroundQuantitative 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.MethodsA 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).ResultsThe 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).ConclusionsModel 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12976-016-0036-3) contains supplementary material, which is available to authorized users.

Highlights

  • 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)

  • While it seems obvious that excluding Ra for glucose and FFA (Combination 1 above) is unnecessary, we present it for completeness so that the difference between Combination 2 and Combination 3 can be clearly exhibited in the progression: no Ra, both Ra’s, only glucose Ra

  • Simulations of each model were performed under four combinations, respectively, dependent on the introduction of glucose/FFA Ra or not and the expression for Ra used: 1) without considering Ra of glucose and FFA; 2) including both glucose and FFA Ra (Type I function); 3) only glucose Ra (Type I function); 4) only glucose Ra (Type II function [40])

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Summary

Introduction

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). Insulin is one of the primary factors regulating plasma glucose and free fatty acid (FFA). The development of insulin resistance and type 2 diabetes (T2D) is closely associated with the abnormal regulation of insulin on carbohydrate metabolism. Dysfunction of whole body lipid metabolism plays an important role in the development of T2D [1,2,3,4]. Quantitation of insulin regulation of glucose and FFA, including kinetic interactions in response to external physiological stimuli, is clinically important because of the potential to inform treatment paradigms for T2D.

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