MBARARA UNIVERSITY OF SCIENCE AND TECHNOLOGY
FACULTY OF APPLIED SCIENCES AND TECHNOLOGY
DEPARTMENT OF BIOMEDICAL SCIENCE AND ENGINEERING
MODELING AND SIMULATION INDIVIDUAL ASSIGNMENT ONE
NAME REG NO.
MUGUMBYA IAN PATRICK 2020/BME/063/PS
MODELLING OF INSULIN GLUCOSE FEEDBACK SYSTEM.
Plasma glucose levels are maintained within relatively narrow limits by a complex regulatory system both
elevated glucose concentration (hyperglycemia) and low glucose concentrations (hypoglycemia) have
serious consequences.
The insulin glucose feedback system is a complex physiological process that regulates the concentration
of glucose in the blood stream through the secretion and action of insulin. In the process of modelling of
insulin glucose feedback system, both the mathematical models and simulation techniques played a
crucial role.
The mathematical model and simulation models plays a crucial role in understanding its dynamic and
developing strategies for diabetes management. Some of the mathematical &simulation models used
includes.
Minimal model (Bergman)
This model commonly refers to as Bergman’s minimal model was published in 1979 and its one of the
most informative computational method for studying glucose and insulin kinetics in metabolism .Its main
intention was to gain a better understanding of the insulin action to clear glucose from circulation. The
model output is summarized into two main parameters, insulin sensitivity and glucose effectiveness.
In the minimal method, the complexity of the glucose-insulin interaction was handled by using insulin
concentrations as known fixed input while modeling parameters related to glucose concentration.
Virtual patient model
The virtual patient models aim to capture the inter-individual variability in glucose insulin dynamics. This
model simulate the behavior of virtual population such as age,weight,insulin sensitivity and beta cell
function and they can be used to assess the variability of treatment responses, optimize therapy and
personal treatment plan.
Closed loop simulation model
Simulation models are often used to design and evaluate closed loop control systems known as artificial
pancreas system .these models integrate glucose measurements, infusion algorithms and prediction
algorithm to simulate closed loop control and evaluate their performance under various conditions.
Pharmacokinetics/Pharmacodynamics models
Pharmacokinetics/Pharmacodynamics models are used to simulate the pharmacokinetics (absorption,
distribution, metabolism and erection) and pharma dynamics (effect on the body) of insulin and glucose
lowering drugs. These models can provide insight into the time course of drug action and aid in
optimizing dosing regiments.
Hovorka model
The hovorka model is a more comprehensive model that incorporates several physiological processes
including glucose absorption from gut, hepatic glucose production considering the nonlinear dynamics of
insulin action allowing for a more accurate representation of insulin glucose system.
Compartmental models
Compartmental models divide the body into different compartments each representing a specific tissue or
organ involved in glucose metabolism. These models use a system of ordinary differential equations to
describe the flow of glucose between compartments and action of insulin on these processes.
Control theory models
Here the principles from control system engineering is applied to regulate glucose levels. These models
use feedback control algorithms to adjust insulin dosing based on continuous glucose monitoring data and
desired targets.
Monte Carlo simulations
Monte Carlo simulation involves running multiple simulations with randomly varied parameters. It is
used to model the probability of different outcomes in a process that cannot easily be predicted due to
intervention of random variables. It requires assigning multiple values to an uncertain variable to achieve
multiple results and averaging the results to obtain an estimate.
Other methods includes the homeostasis model assessment, multiple shooting methods, nonlinear least
square fitting and Gauss newton ,glucose insulin dynamics, program flowchart and coupled ordinary
differential equation solver.
PHARMACOKINETICS MODELS
Pharmacokinetic is defined as the study of the time course of drug absorption, distribution, metabolism
and excretion.
The handling of drug by the body can be very complex as several process work to alter drug concentration
in tissues and fluids.one of the simplifications is to apply mathematical principles to the various
processes.
To apply mathematical principles, a model of the body must be selected .a basic type of model used in
pharmacokinetics is the compartmental model. Compartmental models are categorized by the number of
compartments needed to describe the drug’s behavior in the body.
There are one compartment, two compartment and multi compartment models. The compartment models
do not represent a specific tissue or fluid but may represent a group of similar tissues .these models can be
used to predict the time course of drug concentrations in the body.
For example.
Drug dose Compartment
Elimination
Compartmental models are termed deterministic because the observed drug concentrations determine the
type of compartmental model required to describe the pharmacokinetics of the drug.
One compartment model
This is the most frequently used model in clinical practice. The compartment is represented by an
enclosed square and rates of drug transfer are represented by straight arrows. The arrow pointing into the
box indicates that drug is put into that compartment and the arrow pointing out indicates that drug is
leaving the compartment.
Y
X Z
Where
X=Dose of drug
Y=Amount of drug in the body
Z=elimination rate constant
This model is the simplest since there is only one compartment and all tissues and fluids are considered a
part of this compartment.it I assumed that after a dose is administered, it distributes instantaneously to all
body area.
Two compartment model
Some drugs do not distribute instantaneously to all parts of the body however even after intravenous
bolus administration (administering a dose of drug over a short time period).a common distribution
pattern for the drug to distribute rapidly In the blood stream and to higly perfused organs such as the liver
and kidneys. This pattern of drug distribution may be represented by a two-compartment model where
drugs moves back and forth between these compartments to maintain equilibrium.
Intravenous X Central Y Elimination Z
1 2
Peripheral P
Where
X=dose of drug
Y=amount of drug in the central system
P=Amount of drug in the peripheral system
Z=elimination rate constant of drug from central compartment to outside the body
1=elimination rate constant of drug from peripheral compartment to central compartment..
2=elimination rate constant of drug from central compartment to peripheral compartment.
Mathematically
Drug concentration =amount of drug in body/volume in which drug is distributed
=X/V
Non compartmental model
This model does not rely on specific anatomical compartment but instead analyzes drug concentration
time data directly.it calculates pharmacokinetics parameters such as areas under curve, clearance, volume
f distribution and half-life.
Physiological based pharmacokinetic model
This model takes into account the anatomical and physiological characteristics of different tissues and
organs. They use differential equations to describe drug transport and elimination within the body.
Population pharmacokinetics model
This model takes inter-individual variability into account by analyzing drug concentration data from a
population of individuals. It uses statistical techniques to estimate population parameters and individual
variability.
Monto Carlo simulation
Monte Carlo simulation is a stochastic modelling technique that involves generating random samples to
simulate different scenarios. The simulation are often used to account for inter-individual variability in
pharmacokinetic parameters by sampling from probability distributions of these parameters a large
number of virtual individuals can be simulated.
Virtual patient simulations
This combines pharmacokinetics modeling with patient specific information by incorporating individual
patient characteristics such as weight, age, organ function, genetic variations.
BLOOD CIRCULATORY MODELS
Blood models are mathematical representation of the circulatory system which is responsible for transport
of blood throughout the body. These models aim to describe the flow of blood, pressure changes and
distribution of oxygen, nutrients and waste products within the cardiovascular system.
To under the different parameters including cardiovascular physiology, investigating hemodynamic
parameters and evaluating the impact of various interventions, it crucial to use the following models of
the blood circulatory models.
Electrical circuit models
These models represent the circulatory system as an electrical circuit using electrical analogies to describe
blood flow and pressure .blood vessels are represented as resistors and heart as a pump. The electrical
circuit equations are solved to determine blood flow rates, pressure and other hemodynamic parameters.
Windkessel models
Windkessel models simplify the circulatory system into a few parameters typically the systemically
arterial free and systemic veins. These models incorporates the compliance (elasticity) and resistance of
blood vessels to simulate pressure and flow changes.
The model is useful for studying arterial hemodynamics such as pulse wave propagation and arterial
pressure wave forms.
Computational fluid dynamics
This model simulate blood flow through the vasculature using fluid dynamics principles and
computational techniques. These models employ the naiver strokes equation which govern fluid flow to
predict blood flow patterns, velocities and pressure gradients.
Multi compartmental models
This model divide the circulatory system into multiple compartments representing different regions of the
body or specific organs.
Blood flow and pressure relationships are described using differential equations that account for vessels
properties, resistance and compliance. These models allowed for detailed simulations of blood flow and
oxygen/nutrients delivery to specific organs.
Agent-based models
Agent based model simulates individual components(agents) within the circulatory system such as red
blood cells, platelets and endothelial cells .these models consider the behavior interactions and
characteristics of individual agents to study phenomena such as blood clotting, cell adhesion or
microcirculatory flow.
Neurons.
Biological Neuron Models:
Hodgkin-Huxley Model: Developed by Hodgkin and Huxley in the 1950s, this model describes the
behavior of action potentials in neurons. It incorporates ion channels (sodium, potassium, and leak
channels) and their voltage-dependent conductance’s. The model’s differential equations simulate the
flow of ions across the neuronal membrane, resulting in action potentials.
Fitzhugh-Nagumo Model: A simplified version of the Hodgkin-Huxley model, the Fitzhugh-Nagumo
model reduces the complexity while still capturing essential features. It uses two variables: the
membrane potential and a recovery variable. This model is useful for understanding excitable
behavior in neurons.
Artificial Neuron Models:
McCulloch-Pitts Neuron: An early artificial neuron model, it represents binary logic (firing or not
firing). Inputs are weighted, and if the weighted sum exceeds a threshold, the neuron fires. Although
simplistic, it laid the foundation for neural networks.
Perceptron: Developed by Frank Rosenblatt, the perceptron is a linear classifier. It computes a
weighted sum of inputs and applies an activation function (usually a step function). Perceptrons can
learn simple decision boundaries.
Multi-Layer Perceptron (MLP): An extension of the perceptron, MLPs consist of multiple layers of
interconnected neurons. They can approximate complex functions and are widely used in deep
learning.
Spiking Neural Networks (SNNs):
SNNs model neurons as spiking events rather than continuous potentials. They capture the temporal
dynamics of real neurons.
Leaky Integrate-and-Fire (LIF) Model: A common SNN model, LIF neurons integrate input currents
over time. When the membrane potential crosses a threshold, a spike is generated.
Izhikevich Model: Introduced by Eugene Izhikevich, this model balances simplicity and biological
realism. It can replicate various neuronal behaviors (regular spiking, bursting, etc.).
Simulating Neurons:
Numerical Methods: Differential equations (such as the Hodgkin-Huxley equations) are solved
numerically using methods like Euler’s method or Runge-Kutta. These simulate the dynamics of ion
channels and membrane potentials.
Neural Network Simulators: Tools like NEURON, NEST, and Brian allow researchers to simulate
large-scale neural networks. They provide abstractions for modeling neurons, synapses, and
connectivity.
Computational Efficiency: Simulating large networks requires efficient algorithms and parallel
computing. GPUs and specialized hardware accelerate simulations.
Applications:
Understanding Epilepsy: Neuronal models help study abnormal firing patterns associated with
epilepsy.
Drug Development: Simulations aid in predicting drug effects on neurons and identifying potential
treatments.
Brain-Computer Interfaces: Modeling neurons guides the design of brain-controlled devices.
