(2020) (JAST) Analysis of The Behavior of The Artificial Pancreas

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Abstract Jhon Gómez Portilla, Ruben Hernández, Oscar
F. Avilés. (2020). Analysis of the Behavior of
Diabetes mellitus is a pathology that does not allow the body to adequately the Artificial Pancreas. International Journal of
Advanced Science and Technology, 29(3), 12043
regulate glucose levels, causing hyperglycemia (excessive levels of sugar in Make a Submission
- 12056. Retrieved from
the blood). In the pancreas there is a group of cells known as beta cells,
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managers for synthesizing the hormone insulin, in order to regulate cle/view/30296
glucose. There are various factors that affect these cells and for this reason
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there are deficiencies in the insulin levels required by the human body.
Among the current alternatives to supply the need for insulin in diabetic
patients, there are subcutaneous injections and external infusion pumps, Issue
however, these methods do not offer the desired metabolic control and Vol. 29 No. 3 (2020)
generate discomfort in patients. In recent years, the concept of artificial
Section
pancreas has become very important, which seeks to assimilate to a high
Articles
degree the biological pancreas and solve the drawbacks presented by
current mechanisms. Under the previous premise in this review, the most
current developments regarding these biomedical systems were sought
and described.
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Vol. 29, No. 03, (2020), pp. 12043 - 12056
Jhon Gómez Portilla1, Ruben Hernández2,Oscar F. Avilés3

1,2
Biomedical Department, Nueva Granada Military University
3
Mechatronics Department, Nueva Granada Military University
1
jhon.portilla,2ruben.hernandez, 3oscar.aviles {@unimilitar.edu.co}
Abstract
Diabetes mellitus is a pathology that does not allow the body to adequately regulate
glucose levels, causing hyperglycemia (excessive levels of sugar in the blood). In the
pancreas there is a group of cells known as beta cells, managers for synthesizing the
hormone insulin, in order to regulate glucose. There are various factors that affect these
cells and for this reason there are deficiencies in the insulin levels required by the human
body. Among the current alternatives to supply the need for insulin in diabetic patients,
there are subcutaneous injections and external infusion pumps, however, these methods
do not offer the desired metabolic control and generate discomfort in patients. In recent
years, the concept of artificial pancreas has become very important, which seeks to
assimilate to a high degree the biological pancreas and solve the drawbacks presented by
current mechanisms. Under the previous premise in this review, the most current
developments regarding these biomedical systems were sought and described.
Keywords: Glucometer, hyperglycemia, hypoglycemia, artificial pancreas, MPC, closed-

loop control
1. Introduction
Diabetes mellitus refers to a group of metabolic disorders that share the phenotype of
hyperglycemia. Diabetes Mellitus can be caused by the interaction of genetic and
environmental factors. Factors contributing to hyperglycemia are: Reduced insulin
secretion, decreased glucose utilization, and increased glucose production [1].
Hyperglycemia is a direct consequence of a deficiency in insulin secretion or a
combination of insulin resistance and inadequate insulin secretion to compensate for
resistance. When someone suffers diabetes, the body cannot regulate the amount of sugar
in your blood [2].
Usually, food goes through a process of transformation and is used by the body for
energy. When food is absorbed, a sugar called glucose is generated and enters the
bloodstream (glucose is an energy source for the body). The insulin produced by the
pancreas plays the fundamental role of transporting glucose from the bloodstream to the
muscles, fat and cells, where it can be used as an energy source [3] [4].
When a person suffers diabetes, they have high blood sugar levels because the
pancreas does not produce enough insulin or the cells do not respond normally to insulin
[5].
Among the complications related with the Diabetes include: blindness in adults,
kidney failure, non-traumatic amputation of the lower extremities, coronary heart disease,
gastrointestinal, dermatological problems, blood pressure problems, cholesterol, ulcers,
nerve damage, depression, illnesses bone, dementia, sexual disorders etc. [6] [7].
Insulin is a 51 amino acid polypeptide, and its properties have been extensively
studied. However, insulin is not easily penetrated by biofilms and is destroyed in the
gastrointestinal tract by digestive enzymes, therefore its main administration is by
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ISSN: 2005-4238 IJAST
Copyright ⓒ 2020 SERSC
Vol. 29, No. 03, (2020), pp. 12043 - 12056
subcutaneous injections; This type of insulin administration to regulate the blood sugar
level as well as being uncomfortable for patients generates physical and psychological
problems. Due to the drawbacks of conventional insulin therapy, researchers are engaged
committed to developing new routes for insulin administration. [8] [9].
One of the most used alternatives in recent years for insulin administration are
continuous insulin infusion pumps (BICI) for type 1 diabetes mellitus (DM1), which are
related to better metabolic control when compared to the multiple insulin dose (MDI)
[10].
Continuous infusion pumps have undergone an evolution that allows us to have
smaller and safer devices today; Furthermore, several studies confirm that the use of
BICIs is associated with better glycemic control, including fewer hypoglycemic events
compared to MDIs; however, its use is still very limited due to its high costs. [11].
Aside from being expensive, these insulin pumps are external devices, difficult to
handle for especially elderly patients, and they differ in how the natural pancreas works
because the liver receives a dilute concentration of insulin and the rest of the body
receives too much insulin. (This is the opposite of the normal pattern of insulin
administration in a non-diabetic person) [12].
Due to its high prevalence and the complications that this disease causes, diabetes is
considered one of the most important chronic diseases in public health in the world.
According to the World Health Organization (WHO) between 1980 and 2014 the
incidence of diabetes in the world increased 390%, going from 108 million patients in the
world to 422 million [13].
The world prevalence of this disease has been calculated at 8.5% in 2014. In 2012
alone, diabetes and its complications were estimated to cause 2.2 million deaths
worldwide. According to WHO calculations, in 2030 this disease will be the seventh
leading cause of death in the world [14].
According to DANE statistics, in 2015, 2016, 2017 and 2018, diabetes mellitus was
the fifth leading cause of death in the department of Cundinamarca. Nationwide, from
January to June 2018, 3,769 people died and in 2019 from January to June, 3,658 died.
According to the statistics presented above, diabetes is not only a problem that affects the
population of Cundinamarca, but it also affects the country and the entire world [15].
According to the high cost account (CAC), which is a non-governmental technical
organism of the general social security system, diabetes is a problem that generates high
costs for the individual, the family and the health system. The costs generated by diabetes
are derived from hospital care, access to insulin, daily monitoring of the disease,
concomitant disability, requirement for technical aids, and decreased quality of life. Table
1 shows the annual costs for the general health system by region, which exceed 5 billion
pesos [16].
Table 1. Costs of diabetes mellitus by region [16]
Region DM Cases Total Cost (COP)
Bogotá D.C 211.778 1.016.534.400.000
Atlántico 197.528 948.134.400.000
Central 294.013 1.411.262.400.000
Oriental 194.018 931.286.400.000
Pacifica 191.724 920.275.200.000
Others 10.410 49.968.000.000
National Total 1.099.471 5.277.460.800.000
Average total cost / year per DM case: $ 4.800.000
The epidemiological data, added to the high costs for the different health systems of
the world, show the importance, both in the prevention of said disease and in the
improvement of treatments, to avoid its complications. The most effective treatment for
diabetes is to replace the functions of the pancreas with external devices that inject a
sufficient amount of insulin into the patient's body. These insulin pumps are transported
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by the patient; Its basic function is to supply a basic rate of insulin depending on glucose
levels. To adjust the insulin infusion rate in these devices, patients must permanently
measure their blood glucose. In order for these pumps to deliver the proper amount of
insulin, rigorous monitoring of blood glucose levels is required. [17] [18]
Under the previous premise, there are various investigations that have contributed with
the development of the artificial pancreas, such as: The development of more accurate
biological models of the pancreas and glucose-insulin cycle, sensors for the measurement
of blood glucose in real time, control algorithms to fix the exact amounts of insulin and
smart insulin pumps, which are in charge of supplying the necessary amounts of the
hormone through detailed actuation systems; all of the above is aimed at the possible
design of the implanted pancreas, which would greatly improve the quality of life of
patients with diabetes, in addition to leading the world health systems to significant
savings [19] [20].
The present work seeks to present in detail the current state of the artificial pancreas,
which can be clearly represented by means of a closed-loop physiological control system;
Likewise, it seeks to show what the main drawbacks have been to date that have
prevented the development of implantable technology, which is widely required by
patients with diabetes [21].
2. Biological models oft he pancreas
The insulin glucose cycle model has been worked by several authors since previous
decades, one of the most important is the Richard N. Bergman model. This model is not
linear and has a minimum number of parameters and was called the Bergman minimum
model. In this model it is assumed that the body is a container with a reserve of glucose
and insulin. In effect, the model is divided into two sub-models, one for the minimum
glucose model and the other for the minimal insulin model [22] [23]. The model is
represented by the following mathematical expressions:
𝑑𝐺 (1)
= − 𝑞1 + 𝑋 𝑡 𝐺 𝑡 + 𝑞1 𝐺𝑏
𝑑𝑡
𝑑𝑋 (2)
= −𝑞2 𝑋 𝑡 + 𝑞3 (𝐼 𝑡 − 𝐼𝑏 )
𝑑𝑡
𝑑𝐼 (3)
= −𝑞6 𝐺 𝑡 − 𝑞5 +𝑡 − 𝑞4 (𝐼 𝑡 − 𝐼𝑏 )
𝑑𝑡
Where:
𝐺 𝑡 : Glucose concentration mg/dL
𝑋 𝑡 : Effect of active insulin min−1
𝐼 𝑡 : Insulin concentration(𝜇𝑈 ⁄ 𝑚𝐿)
𝐺𝑏 : Basal glucose value mg/dL
𝐼𝑏 : Basal insulin value(𝜇𝑈 ⁄ 𝑚𝐿)
𝐺 𝑡 − 𝑞5 +: max⁡ (𝐺 𝑡 − 𝑞5 , 0)
In the research carried out by Yisel C villa and Julián García, a new Phenomenological-
based Semi-physical Model (MSBF) of pancreatic function was determined. The model is
based on glucagon and insulin synthesized by the pancreas [24]; the equations are
obtained taking into account the mass flows of blood, insulin and glucagon. The dynamic
model was performed based on an analogy of a three-tank system as shown in Figure 1:
The FDA (U.S. Food and Drug Administration) approved a computerized dynamic
model of the artificial pancreas called the "UvaPadova Type 1 Diabetes Simulator." The
simulator emulates the challenges of feeding in diabetic patients; it has an in-silico
population of 300 patients. Each virtual subject was represented by means of a parametric
vector. The model relates the plasma concentrations of glucose and insulin [25].
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In the research developed by Qian Wang and his team, a new model was developed
based on the dynamics of state spaces, with variable time coefficients, which are used to
quantify their own effects on the metabolism of each patient, such as intake of food, the
fluctuations in glucose and insulin doses. An extended Kalman filter was used to estimate
the time coefficients of the space-state model of the patient [26].
a) Modeling hypothesis b) Process systems

Figure 1 Modeling hypothesis and process systems
In [27] a new mathematical model of pancreatic beta cells is described, which can
explain multimodal patterns. The model includes feedback from 𝐶𝑎2+ cytosolic in the ion
channels; which explains the irruption; and a metabolic system capable of producing slow
oscillations driven by the oscillations of glycolysis.
Alessandro Bertuzzi proposed a system to represent the dynamics of pancreatic beta
cells. Granule translocation and exocytosis are controlled by signals that are assumed to
be related to the ATP-ADP ratio and concentration 𝐶𝑎2+; This model provides an
interpretation of the roles of activation and amplification pathways of glucose-stimulated
insulin secretion. The values of most of the β parameters of the model were deduced from
the available experimental data. Figure 2 shows the granule dynamics for a β cell [28].
The work done by VicenzoPiemonte et al. It is focused on taking into account the main
physiological factors that play an important role in the blood glucose curve over time and
the variability that exists between patients (due to sex, age, weight, lifestyle, among other
physiological factors). ); An important factor to take into account in this model is that it
tries to supply or improve the limits presented by current models in terms of delays
caused by the absorption of subcutaneous tissues and the subcutaneous glucose sensor.
The presented system is based on three components: the plasma compartment, the ISF
compartment and the SC compartment to simulate the dynamics of insulin in
subcutaneous tissue [29].
Figure 2. Diagram of the kinetics of a group of granules in β cells. I, group of

proinsulin aggregates; V, group of granules of the membrane material; R, reserve
group; D, Group of coupled granules; F group of granules fused with the plasma
membrane. The amount σF represents the number of insulin granules, which, over a
period of time, release insulin into the extracellular space [28].
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The simplicity of the biological models of the glucose-insulin cycle greatly facilitate
the development of more precise control techniques, in [30] a simple non-linear model is
described to simulate data from experiments where insulin bolus are administered in the
cavity peritoneal. The developed model takes into account the delays between insulin
administration and its non-linear transport to other compartments. The model is given by
the following equations:
𝑑𝐺
= − 𝑘0 + 𝑘1 ∙ 𝐼 𝑡 ∙ 𝐺 𝑡 + 𝑗 ∙ 𝐽(𝑡) (4)
𝑑𝑡
𝑑𝐼
= −𝑎1 ∙ 𝐼 𝑡 + 𝑎2 ∙ [𝑖1 (𝑡)] 𝑝 (5)
𝑑𝑡
𝑑𝑖1
= −𝑎3 ∙ 𝑖1 𝑡 + 𝑎4 ∙ 𝐼 𝑡 + 𝑎6 ∙ 𝑖2 𝑡 (6)
𝑑𝑡
𝑑𝑖2
= −𝑎6 ∙ 𝑖2 𝑡 + 𝑎5 ∙ 𝑖1 𝑡 + 𝑘 ∙ 𝐾 𝑡 (7)
𝑑𝑡
Where
𝐺: Blood glucose concentration
𝐼: Insulin concentration in the blood
𝑖1 , 𝑖2 ∶Insulin transport rates
𝐽 𝑡 , 𝐾(𝑡) : Non-negative functions representing exogenous glucose infusion rate and
insulin administration.
𝑎𝑖 , 𝑗, 𝑘, 𝑘0 , 𝑘1 : Positive parameters depending on the person
Continuous glucose monitoring (CGM) systems provide the glucose measurements, so

that controllers determine the necessary amounts of insulin to be injected into the patient's
body, through insulin pumps using a closed loop system [31]
Below are the most important control techniques that have been applied to biological
models of the pancreas in recent years.
2.1 Control algorithms

In the work carried out by Dylan Calupiña and his team, the development of two
controllers for the UVA / PADOVA plant is presented, which simulates the dynamics of
the glucose-insulin cycle. The first controller is a nonlinear PID which introduces
nonlinear functions for the error produced by the gain of the variables depending on the
value of the functions [32].
The non-linear PID starts from the combination of non-linear functions, which depend
on the proportional, integral and derivative error respectively.
𝛼𝑝
𝑒𝑝 ∗ 𝑠𝑖𝑔𝑛 𝑒𝑝 , 𝑒𝑝 > 𝛿
𝑓𝑎𝑙 𝑒𝑝 , 𝛼𝑝 , 𝛿 = 𝑒𝑝 (8)
𝑒 ≤ 𝛿
𝛿 1 − 𝛼𝑝 ′ 𝑝
𝑒𝑖 𝛼 𝑖 ∗ 𝑠𝑖𝑔𝑛 𝑒𝑖 , 𝑒𝑖 > 𝛿
𝑓𝑎𝑙 𝑒𝑖 , 𝛼𝑖 , 𝛿 = 𝑒𝑖 (9)
𝑒 ≤ 𝛿
𝛿 1 − 𝛼𝑖 ′ 𝑖
𝑒𝑑 𝛼 𝑑 ∗ 𝑠𝑖𝑔𝑛 𝑒𝑑 , 𝑒𝑑 > 𝛿
𝑓𝑎𝑙 𝑒𝑑 , 𝛼𝑑 , 𝛿 = 𝑒𝑑 (10)
𝑒 ≤ 𝛿
𝛿 1 − 𝛼𝑑 ′ 𝑑
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Vol. 29, No. 03, (2020), pp. 12043 - 12056
Where 𝑒𝑝 is the proportional error,𝑒𝑖 is the integrative error and𝑒𝑑 is the derivative
error. 𝛼𝑝 ,𝛼𝑖 , 𝛼𝑑 It is the tuning constants, which vary the nonlinear function. The sliding
mode controller has the advantage of being highly robust against external disturbances
and variations in plant parameters [33].
Alexander James Barnes et al, used the continuous intraperitoneal infusion system as a
reference, which greatly simplifies the control problem by reducing the delay in insulin
absorption. The team developed a comparison between a CSII system (continuous
subcutaneous insulin infusion) that uses an MPC control and its development which is
based on a PID on a CIPII system [34]. In general terms, the design of the PID presented
good results, although three of the individual subjects in-silico presented hypoglycemia, it
was recently discovered that the (PID-IFB) limits the oscillations of glucose [35].
In the developed work out by Nalini M and his team, a controller for type 1 diabetes
was implemented using a non-linear model, which was simulated in Matlab Simulink
using a predictive model control (MPC). The blood glucose regulation system uses a
sensor and a controller, the latter send a control action that decides the amount of insulin
to be injected; the basic structure of the MPC is shown in figure 3. Based on past and
present values, the model is used to predict future plant outputs; the future of the inputs is
given by the model and the actions are calculated with the optimizer, considering the cost
functions [36]. Figure 4 illustratesthe block diagram of theproposedarchitecture [37].
Figure 3. Basic structure of an MPC Figure 4. Block diagram
Inside the predictive controllers by model, architectures based on artificial intelligence

systems are found; as is the case of the work developed by SaeidBahremand et al, in
which a neural network for the prediction of the level of glucose in the blood based on
different inputs and a MPC (model predictive control) for glycemic control are combined.
In this work, in-silico subjects were used as test patients in order to generate the data sets
to train the neural networks and the NN-MPC determines the control actions based on the
blood glucose levels that have been estimated by the same artificial network [38].
In 2015, Ivan Sekaj developed an adaptive controller using genetic algorithms, applied
to the Bergman minimum model. Genetic algorithms allow to identify the patient's model
and also contribute to the design of the controller. Figure 5 shows the block diagram of
the blood glucose controller MRAC (Model reference Adaptive Controller) [39].
Figure 5. Glycemic control with closed-loop feedback
Currently, the concept of control based on data obtained from glucose sensors has
gained considerable strength. These systems are defined by three key elements such as: A
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Vol. 29, No. 03, (2020), pp. 12043 - 12056
continuous glucose monitoring system, an infusion system (actuator) and a control
algorithm. The individual development of each of these elements has had an impact on
each other. The development of CGM (Continuous Glucose Monitoring) systems has
allowed designers of control techniques to have a large amount of data on glucose
metabolism in diabetic patients; Thanks to this, several data-based control algorithms
have been developed [40].
Chiara Toffanin used a learning-based control algorithm, to automate the basal index,
using as reference real-time measurements from a CGM sensor, the technique takes the
name of ―run to run‖ (R2R). This type of control is normally used in highly demanding
chemical processes. To improve its performance, the algorithm learns information about
the current execution and modifies the control technique that will be applied in the next
execution. The algorithm, for an execution 𝑘, the update of the control law for each
interval 𝑗:
𝑏𝑗 𝑘 − 𝑏𝑗 𝑘1𝑗 𝑇𝑏𝑗 𝑘 𝑆𝑖 𝑇𝑏𝑗 𝑘 > 0

𝑏𝑗 𝑘 + 1 = 𝐺𝑚𝑗 𝑘 − 𝐺𝑇𝑗 (11)
𝑏𝑗 𝑘 + 𝑏𝑗 𝑘2𝑗 𝑇𝑎𝑗 𝑘 + 𝑘3𝑗 𝑆𝑖 𝑇𝑏𝑗 𝑘 > 0
𝐺𝑇𝑗
Where𝑏𝑗 is the insulin administration during interval 𝑗 and the variable updated by the
algorithm, the constants 𝑘1𝑗 , 𝑘2𝑗 , 𝑘3𝑗 are the R2R earnings, 𝐺𝑇𝑗 is the desired blood glucose
level and𝑇𝑏𝑗 , 𝑇𝑎𝑗 , 𝐺𝑚𝑗 are the performance indices associated with the interval j[41].
In the development of MPC controllers, it is worth noting the research developed by
Dimitri Boiroux Et al; in which a closed-loop control system is operated, where a
continuous glucose sensor, a continuous insulin infusion pump and an MPC control
algorithm are used. In this system, the data required for optimal controller operation are:
The basal insulin infusion rate, insulin sensitivity factor, and insulin action time. This
MPC uses an asymmetric objective function that greatly prevents hypoglycemia. The
model used by the MPC for filtering and prediction is autoregressive integrated with the
exogenous input model (ARIMAX) [42].
In 2017 YueRuan Et al, they used a glucose sensor to take samples every 10 minutes;
Insulin administration and food intake were analyzed for eight adults with type 1 diabetes
mellitus. A closed-loop system was used for this study for twelve weeks. The
implemented algorithm consists of five differential equations and the model parameters
were estimated using the Monte Carlo approach within a Bayesian model [43].
As it has been presented up to now, in the literature there are PID controllers
(proportional - integral - derivative) [44], MPC (predictive control by model) [45],
generalized predictive control (CPG) [46]; however, it should be borne in mind that these
controllers are mostly model-based, that is, an insulin and glucose control model is
needed; but it is complex to work with the parameters and variables that are needed, given
the nonlinearities presented in food administration and the physiological differences that
exist between patients. For the reasons stated above, an important controller option arises,
such as the Fuzzy controller; This fuzzy logic-based controller is promising to deal with
nonlinearities and is insensitive to changing physiological parameters [47] [48]. On the
other hand, many studies have confirmed that hybrid controls can be performed that
combine PID techniques with Fuzzy [49].
Some studies found in the literature use food detection algorithms or manuals with
nutritional information; in the construction of the artificial pancreas this should be
avoided since this is expected to be fully automated [50] [51].
SelimSoylu Et al, developed a fuzzy mamdani P + D type system (hybrid), the
optimization process was executed by a global algorithm based on swarms. The fuzzy P +
D strategy was proposed in order to improve the performance of the PD controller, with
the diffuse P part. As inputs to the fuzzy controller, only the error and the error of the rate
of change of the glucose concentration in the blood of each patient were taken into
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account, since the main objective was to make the artificial pancreas as automatic as
possible [52].
Once mentioned in the literature regarding control systems and different algorithms,
some of the continuous glucose sensors are presented below, which are very important in
the development of the artificial pancreas, since the controllers take these data as a
reference to carry out control actions.
2.2 Continuous glucose monitoring

Figure 6 shows a diagram with the main glucose monitoring systems [53].
Figure 6. Blood glucose measurement devices and systems
ZhiuaPu and his team developed a device to monitor glucose continuously, using a
system of self-calibrated epidermal micro-fluids based on differential sodium. The system
is made up of an epidermal detection patch and micro skin channels, which integrates a
pair of extraction electrodes, an electrochemical glucose sensor and a differential sodium
sensor. Figure 7 shows a schematic diagram of the developed solution, and Figure 8
shows the working principle [54].
Figure 7. Schematic diagram of the sodium-based self-calibrating differential epidermal

detection patch. The patch includes a pair of electrodes for interstitial fluid extraction, a
flexible electrochemical glucose sensor, and a sodium differential sensor
Figure 8. Working principle of the sodium-based self-calibrating differential epidermal

microfluidic system
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The Nano Engineering department of the University of California, in conjunction with
the Sao Carlos Institute of Physics of the University of Sao Paulo, implemented a portable
bioelectronic tear sensor, which by means of lenses can measure the glucose levels found
in the tears. The biosensor detects an enzyme known as glucose oxidase found in tears,
which is used to measure glucose found in body fluids. The device sends the results in
real time to computers or Smartphone. Figure 9 shows the lens-based fluid device [55].
Figure 9. Proposed biosensor (A) Representation of glucose detection (a) and detection of
vitamins (b). For the enzymatic detection of glucose, the enzymatic reaction is presented
showing the oxidation of glucose in the tear. For vitamin detection a typical SWV response is
shown indicating the peaks for vitamins B2, C and B6. (B) Exploded view of the fluid device:
(1) carbonated upper membrane (2) double adl spacer (3) outlet sheet (4) electrochemical
sensor (5) polycarbonate lower membrane. The right part of figure B corresponds to the tear
stimulator
Within the CGM (Continuous Glucose Monitor) there are non-invasive systems,
RagdaMamoun Et al, developed a system for the continuous measurement of blood sugar
levels with an accuracy of 89%, by calculating glucose levels Using the voltage obtained
by means of a pulse oximeter as a reference, this working group obtained an equation
using linear regression in Excel. Since the pulse oximeter probe is used as a non-invasive
means for glucose detection, equation 12 that relates them was used [56] [57]:
𝐺 = 𝜀𝑆 + 𝜆𝐴 + 𝛼𝑉 − 𝛽 (12)
Where:
𝑆: Sex of the patient "Male = 0, Female = 1"
𝐴: Age of the patients
𝐺: Blood glucose concentration ―mg/dl‖
𝑉: ADC output voltage
𝜀 = 19.71, 𝜆 = 4.15, 𝛼 = 9.27, 𝛽 = 54.16
One of the most recent developments of a CGM sensor, occurred in the year 2020,
through research developed by Amin Fatoni Et al, who developed a glucose biosensor
based on the technique of real-time colorimetry, which uses electronic components LDR,
TCS230 and a web cam. Detection was based on recognition of the hydrogen peroxide
and titanium oxysulfate reaction by the intensity of the resulting yellow color on the RGB
scale. In this investigation the TCS230 color sensor generates a linear output, which is
very helpful in processing [58].
Within implantable glucose sensor technologies, a team of researchers from the
California Institute of Technology developed a sensor for the measurement of
subcutaneous glycemia based on a CMOS platform. In their design they used an
electrochemical technique with a potentiostatic system. The potentiostat with the help of
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an ADC records the sensor signal on the chip. The electrodes used were Pt – Ag/AgCl and
the enzyme glucose oxidase was used to allow the measurement of glucose [59].
Interstitial fluids have been a focus of research in recent years for the measurement of
glycemia, through the innovation of different biosensors, as is the case of the work carried
out by Hyunsik Kim Et al, this research team developed a minimally invasive biosensor
type portable patch with micro needles for continuous monitoring of glucose in interstitial
fluid (ISF). As the sensor micro needles are inserted into the skin, the characteristics of
the biomaterial and the ability to stretch were taken into account. Figure 10 shows the
developed system [60]:
Figure 10.Conceptual diagram of the attachable and implantable glucose sensor in

the skin
3. Conclusions
The development of a 100% functional, automated and biocompatible pancreas is one
of the most important projects, in order to improve the quality of life of diabetic patients.
In this review, each of the stages that make up the artificial pancreas in closed loop
configuration, which are: Biological model of pancreatic beta cells, control algorithm and
continuous glucose monitoring sensors.
As of today, the artificial pancreas systems are not entirely perfect, since the control
problem is complicated, in the sense of the variability of the different parameters such as:
food intake, variable variables from patient to patient, emotional situations like stress.
Controllers continue to risk supplying insulin than patients require, although in a small
percentage, this can lead to hyperglycemia or hypoglycemia.
However, the advances are encouraging in terms of the benefit it brings to diabetic
patients, with a progressive change from current multiple-dose insulin therapies, which
generate physical and psychological problems. Currently there are commercial insulin
pumps that already have control algorithms to stop the infusion in the case of possible
hypoglycemia.
In the next few years you can see a fully implantable artificial pancreas, which fulfills
the synthesis and diffusion function of the insulin hormone, with fully biocompatible
biomaterials; In this way the existing mechanisms for the treatment of diabetes would be
replaced. In general, improvements in dynamic glucose-insulin systems are expected to
emerge to avoid variability in model parameters.
Acknowledgments
The research for this study was supported by Nueva Granada Military University in
Bogota - Colombia
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Vol. 29, No. 03, (2020), pp. 12043 - 12056
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Home / Archives / Vol. 29 No. 3 (2020) / Articles

Analysis of the Behavior of the Artificial Pancreas

Jhon Gómez Portilla, Ruben Hernández, Oscar F. Avilés  PDF

Publication Ethics and Malpractice

Analysis of the Behavior of the Artificial Pancreas

Jhon Gómez Portilla1, Ruben Hernández2,Oscar F. Avilés3

Keywords: Glucometer, hyperglycemia, hypoglycemia, artificial pancreas, MPC, closed-

2. Biological models oft he pancreas

a) Modeling hypothesis b) Process systems

Figure 2. Diagram of the kinetics of a group of granules in β cells. I, group of

Continuous glucose monitoring (CGM) systems provide the glucose measurements, so

2.1 Control algorithms

Figure 3. Basic structure of an MPC Figure 4. Block diagram

Inside the predictive controllers by model, architectures based on artificial intelligence

Figure 5. Glycemic control with closed-loop feedback

𝑏𝑗 𝑘 − 𝑏𝑗 𝑘1𝑗 𝑇𝑏𝑗 𝑘 𝑆𝑖 𝑇𝑏𝑗 𝑘 > 0

2.2 Continuous glucose monitoring

Figure 6. Blood glucose measurement devices and systems

Figure 7. Schematic diagram of the sodium-based self-calibrating differential epidermal

Figure 8. Working principle of the sodium-based self-calibrating differential epidermal

Figure 10.Conceptual diagram of the attachable and implantable glucose sensor in

[1] A. C. Powers, K. D. Niswender, and C. Evans-Molina, ―Diabetes Mellitus: Diagnosis,

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