Tomas Koutny

Modeling of compartment reaction delay and glucose travel time through interstitial fluid in reaction to a change of glucose concentration

Change of glucose concentration in the blood causes a change of glucose concentration in the interstitial fluid. Glucose enters the interstitial fluid from the bloodstream. Eventually, glucose leaves the interstitial fluid after some time. Its concentration in the interstitial fluid does not necessarily copy a progress of the blood concentration immediately. There is a reaction delay caused by regulatory mechanisms. In this paper, I propose two models, which demonstrate effects of the reaction delay and the glucose travel time through the interstitial fluid.

Blood glucose level reconstruction as a function of transcapillary glucose transport

A diabetic patient occasionally undergoes a detailed monitoring of their glucose levels. Over the course of a few days, a monitoring system provides a detailed track of their interstitial fluid glucose levels measured in their subcutaneous tissue. A discrepancy in the blood and interstitial fluid glucose levels is unimportant because the blood glucose levels are not measured continuously. Approximately five blood glucose level samples are taken per day, and the interstitial fluid glucose level is usually measured every 5min. An increased frequency of blood glucose level sampling would cause discomfort for the patient; thus, there is a need for methods to estimate blood glucose levels from the glucose levels measured in subcutaneous tissue. The Steil-Rebrin model is widely used to describe the relationship between blood and interstitial fluid glucose dynamics. However, we measured glucose level patterns for which the Steil-Rebrin model does not hold. Therefore, we based our research on a different model that relates present blood and interstitial fluid glucose levels to future interstitial fluid glucose levels. Using this model, we derived an improved model for calculating blood glucose levels. In the experiments conducted, this model outperformed the Steil-Rebrin model while introducing no additional requirements for glucose sample collection. In subcutaneous tissue, 26.71% of the calculated blood glucose levels had absolute values of relative differences from smoothed measured blood glucose levels less than or equal to 5% using the Steil-Rebrin model. However, the same difference interval was encountered in 63.01% of the calculated blood glucose levels using the proposed model. In addition, 79.45% of the levels calculated with the Steil-Rebrin model compared with 95.21% of the levels calculated with the proposed model had 20% difference intervals.

Glucose predictability, blood capillary permeability, and glucose utilization rate in subcutaneous, skeletal muscle, and visceral fat tissues

This study suggests an approach for the comparison and evaluation of particular compartments with modest experimental setup costs. A glucose level prediction model was used to evaluate the compartments glucose transport rate across the blood capillary membrane and the glucose utilization rate by the cells. The glucose levels of the blood, subcutaneous tissue, skeletal muscle tissue, and visceral fat were obtained in experiments conducted on hereditary hypertriglyceridemic rats. After the blood glucose level had undergone a rapid change, the experimenter attempted to reach a steady blood glucose level by manually correcting the glucose infusion rate and maintaining a constant insulin infusion rate. The interstitial fluid glucose levels of subcutaneous tissue, skeletal muscle tissue, and visceral fat were evaluated to determine the reaction delay compared with the change in the blood glucose level, the interstitial fluid glucose level predictability, the blood capillary permeability, the effect of the concentration gradient, and the glucose utilization rate. Based on these data, the glucose transport rate across the capillary membrane and the utilization rate in a particular tissue were determined. The rates obtained were successfully verified against positron emission tomography experiments. The subcutaneous tissue exhibits the lowest and the most predictable glucose utilization rate, whereas the skeletal muscle tissue has the greatest glucose utilization rate. In contrast, the visceral fat is the least predictable and has the shortest reaction delay compared with the change in the blood glucose level. The reaction delays obtained for the subcutaneous tissue and skeletal muscle tissue were found to be approximately equal using a metric based on the time required to reach half of the increase in the interstitial fluid glucose level.

Prediction of Interstitial Glucose Level

Glucose is an important source of energy for cells. In clinical practice, we measure glucose level in blood and interstitial fluid. Each method has its pros and cons, and both levels correlate with each other. As the body tries to maintain the glucose level within a particular range to avoid adverse effects, it is desirable to predict future glucose levels in order to aid provided health care. We can see this desire in research, e.g., research on glucose transporters of cells. As yet another example, we can see it with diabetic patients, patients in a metabolic intensive care unit, particularly. In this paper, a glucose level prediction method is proposed.

Estimating reaction delay for glucose level prediction

The pancreas, liver and hypothalamus have a regulatory function in the glucose homeostasis. As the blood glucose level changes, these compartments react and the level changes again. Subsequently to this reaction, the interstitial glucose level changes with some delay. In this paper, I propose a hypothesis that the change of the blood glucose level includes information about the estimated rate with which the hypothalamus expects the blood glucose level to return to normal range, by means of regulatory mechanisms of glucose homeostasis. As the interstitial glucose level change reflects the blood glucose level change, I propose a method to estimate the blood-to-interstitial glucose level delay. It is an important factor for glucose level prediction. Once the delay was calculated, it was possible to relate the present blood glucose level and future interstitial glucose level with such coefficients, which do not seem to change over the time of the experiment to a significant extent. Perhaps, it is a parameterization of regulatory processes of glucose homeostasis, which could be possibly encoded within hypothalamus set-points. The delays were constant per subject and ranged from 7 min up to 34 min for hereditary hypertriglyceridemic rats of 230-480 g weight, in experiments with a variable glucose infusion rate.

Glucose-Level Interpolation for Determining Glucose Distribution Delay

As a part of research on glucose transporters, I already proposed a hypothesis that the change of the blood glucose level includes information about the estimated rate with which the hypothalamus expects the blood glucose level to return to normal range, by means of regulatory mechanisms of glucose homeostasis. As the interstitial glucose level change reflects the blood glucose level change, I proposed a method to estimate the blood-to-interstitial glucose level delay prior formulating the hypothesis. For the estimation, measured glucose levels can be either approximated or interpolated. Each method has its pros and cons. However, the estimated delay converges into narrower bounds, as more glucose levels are measured, if the measured glucose levels are interpolated. In this paper, I present further details on the interpolation method which were not presented in previously published papers.

Detecting Unauthorized Modification of HTTP Communication with Steganography

HTTP does not secure its requests and responses. Using Man-in-the-Middle attack, it is possible to alter the HTTP communication, while it still would look authentic. This can be a problem, if you download data such as PGP key, TOR client, access banking services on-line, or when there is an interest to filter what you can read on the Internet. It should be noted that under particular circumstances, it is possible to attack HTTPS secured communication successfully. This paper proposes a steganography scheme that can be used to detect unauthorized modifications of HTTP communication.

Using meta-differential evolution to enhance a calculation of a continuous blood glucose level

We developed a new model of glucose dynamics. The model calculates blood glucose level as a function of transcapillary glucose transport. In previous studies, we validated the model with animal experiments. We used analytical method to determine model parameters. In this study, we validate the model with subjects with type 1 diabetes. In addition, we combine the analytic method with meta-differential evolution. To validate the model with human patients, we obtained a data set of type 1 diabetes study that was coordinated by Jaeb Center for Health Research. We calculated a continuous blood glucose level from continuously measured interstitial fluid glucose level. We used 6 different scenarios to ensure robust validation of the calculation. Over 96% of calculated blood glucose levels fit A+B zones of the Clarke Error Grid. No data set required any correction of model parameters during the time course of measuring. We successfully verified the possibility of calculating a continuous blood glucose level of subjects with type 1 diabetes. This study signals a successful transition of our research from an animal experiment to a human patient. Researchers can test our model with their data on-line at https://diabetes.zcu.cz.

On-line Blood Glucose Level Calculation

Diabetes is a silent disease. It is the 8th most common cause of death that does not hurt until it is too late and the disease has developed. Technology plays a vital role in managing diabetes and educating patients about importance of the treatment. The patient must be able to manage his blood glucose level. However, blood glucose level is measured sporadically as it causes important discomfort to the patient. Measuring glucose level in subcutaneous tissue is minimally invasive technique and thus considerably comfortable, but this level may be different from blood glucose level. We implemented a recently proposed method of blood glucose level calculation from the continuously measured subcutaneous tissue glucose level. Then, we developed a web portal that makes this method accessible to any doctors office and any diabetic patient. To the best of our knowledge, we are the very first web portal that does this. In this paper, we describe the portal.

An Evolutionary Approach for Estimating the Blood Glucose by Exploiting Interstitial Glucose Measurements

The diabetes is correlated to a malfunction of the pancreas that produces very little or no insulin. A way to improve the quality of life of people with diabetes is to implement an artificial pancreas able to inject an insulin bolus when necessary. The aim of this paper is to devise a possibly step in constructing the fundamental element of such an artificial pancreas estimation of the blood glucose (BG) through interstitial glucose (IG) measurements. In particular, a new methodology is presented to derive a mathematical relationship between BG and IG by exploiting the ability of the evolutionary techniques in solving this regression task. An automatic procedure is used to estimate the missing BG values within this database. To validate the discovered model a comparison with other models is carried out during the experimental phase.