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Modeling and Measurement of Correlation between Blood and Interstitial Glucose Changes.

Shi T, Li D, Li G, Zhang Y, Xu K, Lu L - J Diabetes Res (2016)

Bottom Line: Computer simulation mimicked curves were fitted with data resulting from fluorescent measurements of mice and isotope measurements of rats, indicating that there were lag times for ISF glucose changes.It also showed that there was a required diffusion distance for glucose to travel from center of capillaries to interstitial space in both mouse and rat models.We conclude that it is feasible with the developed model to continuously monitor dynamic changes of blood glucose concentration through measuring glucose changes in ISF with high accuracy, which requires correct parameters for determining and compensating for the delay time of glucose changes in ISF.

View Article: PubMed Central - PubMed

Affiliation: College of Electronic Information and Control Engineering, Beijing University of Technology, Beijing 100124, China; State Key Laboratory of Precision Measuring Technology and Instruments, Tianjin University, Tianjin 300072, China; Department of Medicine, University of California School of Medicine, Torrance, CA 90502, USA.

ABSTRACT
One of the most effective methods for continuous blood glucose monitoring is to continuously measure glucose in the interstitial fluid (ISF). However, multiple physiological factors can modulate glucose concentrations and affect the lag phase between blood and ISF glucose changes. This study aims to develop a compensatory tool for measuring the delay in ISF glucose variations in reference to blood glucose changes. A theoretical model was developed based on biophysics and physiology of glucose transport in the microcirculation system. Blood and interstitial fluid glucose changes were measured in mice and rats by fluorescent and isotope methods, respectively. Computer simulation mimicked curves were fitted with data resulting from fluorescent measurements of mice and isotope measurements of rats, indicating that there were lag times for ISF glucose changes. It also showed that there was a required diffusion distance for glucose to travel from center of capillaries to interstitial space in both mouse and rat models. We conclude that it is feasible with the developed model to continuously monitor dynamic changes of blood glucose concentration through measuring glucose changes in ISF with high accuracy, which requires correct parameters for determining and compensating for the delay time of glucose changes in ISF.

No MeSH data available.


Measurements of blood and ISF glucose changes in mice. (a) Time course of blood and ISF glucose concentration changes in mice. (b) Comparisons of glucose changes measured in blood (BG) and interstitial fluid (ISFG) of mice with the time courses generated by the theoretical simulations. For the in vivo studies, six experimental mice (three male and three female) with similar size and weight were used. The mice were fasted for one night before the experiment. F is the blood flow and P is the glucose extraction from blood related to glucose membrane permeability ensued in the theoretical model.
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fig2: Measurements of blood and ISF glucose changes in mice. (a) Time course of blood and ISF glucose concentration changes in mice. (b) Comparisons of glucose changes measured in blood (BG) and interstitial fluid (ISFG) of mice with the time courses generated by the theoretical simulations. For the in vivo studies, six experimental mice (three male and three female) with similar size and weight were used. The mice were fasted for one night before the experiment. F is the blood flow and P is the glucose extraction from blood related to glucose membrane permeability ensued in the theoretical model.

Mentions: The correlation of blood and ISF glucose concentration changes was measured by detecting intensity of fluorescent alizarin-borate polymer (ABP) that was embedded under the skin in abdominal region of mice. Glucose specifically binds to the borate polymer in ABP resulting in fluorescent ABP to decompose into nonfluorescent alizarin and changed fluorescence intensity can be quantified to determine the concentrations of the added glucose molecules. At the same time points, venous blood samples were obtained and blood glucose concentrations were measured in a 96-well microplate containing ABP. A time course of fluorescent intensity changes that were calibrated to reflect glucose concentrations was plotted to demonstrate ISF and reference blood glucose concentrations (Figure 2(a)). Changes of blood and ISF glucose concentrations measured by fluorescent detection method verified the mathematical model presented in Figure 1. All values obtained from measurement of ISF glucose concentrations in mice were plotted in the mathematical simulation model to yield the referenced blood and ISF glucose concentrations with previous fixed physiological parameters (Figure 2(b)). The maximum and average relative error (abs(measured − predicted)/measured) were 38.16% and 16.42% (F = 3, P = 25), 43.01% and 19.12% (F = 3, P = 20), and 51.72% and 24.29% (F = 2, P = 10), respectively. Results of measured time courses of blood and ISF glucose concentrations with fluorescent method were matched with predicted blood and ISF glucose concentration changes simulated by the mathematical simulation model, indicating that the model simulated blood and ISF glucose changes may be used for prediction of the correlation of blood and ISF glucose levels following a physiologically related time course.


Modeling and Measurement of Correlation between Blood and Interstitial Glucose Changes.

Shi T, Li D, Li G, Zhang Y, Xu K, Lu L - J Diabetes Res (2016)

Measurements of blood and ISF glucose changes in mice. (a) Time course of blood and ISF glucose concentration changes in mice. (b) Comparisons of glucose changes measured in blood (BG) and interstitial fluid (ISFG) of mice with the time courses generated by the theoretical simulations. For the in vivo studies, six experimental mice (three male and three female) with similar size and weight were used. The mice were fasted for one night before the experiment. F is the blood flow and P is the glucose extraction from blood related to glucose membrane permeability ensued in the theoretical model.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4863111&req=5

fig2: Measurements of blood and ISF glucose changes in mice. (a) Time course of blood and ISF glucose concentration changes in mice. (b) Comparisons of glucose changes measured in blood (BG) and interstitial fluid (ISFG) of mice with the time courses generated by the theoretical simulations. For the in vivo studies, six experimental mice (three male and three female) with similar size and weight were used. The mice were fasted for one night before the experiment. F is the blood flow and P is the glucose extraction from blood related to glucose membrane permeability ensued in the theoretical model.
Mentions: The correlation of blood and ISF glucose concentration changes was measured by detecting intensity of fluorescent alizarin-borate polymer (ABP) that was embedded under the skin in abdominal region of mice. Glucose specifically binds to the borate polymer in ABP resulting in fluorescent ABP to decompose into nonfluorescent alizarin and changed fluorescence intensity can be quantified to determine the concentrations of the added glucose molecules. At the same time points, venous blood samples were obtained and blood glucose concentrations were measured in a 96-well microplate containing ABP. A time course of fluorescent intensity changes that were calibrated to reflect glucose concentrations was plotted to demonstrate ISF and reference blood glucose concentrations (Figure 2(a)). Changes of blood and ISF glucose concentrations measured by fluorescent detection method verified the mathematical model presented in Figure 1. All values obtained from measurement of ISF glucose concentrations in mice were plotted in the mathematical simulation model to yield the referenced blood and ISF glucose concentrations with previous fixed physiological parameters (Figure 2(b)). The maximum and average relative error (abs(measured − predicted)/measured) were 38.16% and 16.42% (F = 3, P = 25), 43.01% and 19.12% (F = 3, P = 20), and 51.72% and 24.29% (F = 2, P = 10), respectively. Results of measured time courses of blood and ISF glucose concentrations with fluorescent method were matched with predicted blood and ISF glucose concentration changes simulated by the mathematical simulation model, indicating that the model simulated blood and ISF glucose changes may be used for prediction of the correlation of blood and ISF glucose levels following a physiologically related time course.

Bottom Line: Computer simulation mimicked curves were fitted with data resulting from fluorescent measurements of mice and isotope measurements of rats, indicating that there were lag times for ISF glucose changes.It also showed that there was a required diffusion distance for glucose to travel from center of capillaries to interstitial space in both mouse and rat models.We conclude that it is feasible with the developed model to continuously monitor dynamic changes of blood glucose concentration through measuring glucose changes in ISF with high accuracy, which requires correct parameters for determining and compensating for the delay time of glucose changes in ISF.

View Article: PubMed Central - PubMed

Affiliation: College of Electronic Information and Control Engineering, Beijing University of Technology, Beijing 100124, China; State Key Laboratory of Precision Measuring Technology and Instruments, Tianjin University, Tianjin 300072, China; Department of Medicine, University of California School of Medicine, Torrance, CA 90502, USA.

ABSTRACT
One of the most effective methods for continuous blood glucose monitoring is to continuously measure glucose in the interstitial fluid (ISF). However, multiple physiological factors can modulate glucose concentrations and affect the lag phase between blood and ISF glucose changes. This study aims to develop a compensatory tool for measuring the delay in ISF glucose variations in reference to blood glucose changes. A theoretical model was developed based on biophysics and physiology of glucose transport in the microcirculation system. Blood and interstitial fluid glucose changes were measured in mice and rats by fluorescent and isotope methods, respectively. Computer simulation mimicked curves were fitted with data resulting from fluorescent measurements of mice and isotope measurements of rats, indicating that there were lag times for ISF glucose changes. It also showed that there was a required diffusion distance for glucose to travel from center of capillaries to interstitial space in both mouse and rat models. We conclude that it is feasible with the developed model to continuously monitor dynamic changes of blood glucose concentration through measuring glucose changes in ISF with high accuracy, which requires correct parameters for determining and compensating for the delay time of glucose changes in ISF.

No MeSH data available.