American Journal of Computational Mathematics, 2018, 8, 233-244

http://www.scirp.org/journal/ajcm
ISSN Online: 2161-1211
ISSN Print: 2161-1203

Simplified Mathematical Model of

Glucose-Insulin System

Jean Marie Ntaganda1, Froduald Minani1, Wellars Banzi1, Lydie Mpinganzima1,

Japhet Niyobuhungiro1, Jean Bosco Gahutu2, Eric Rutaganda2,
Immaculate Kambutse2, Vincent Dusabejambo2

Department of Mathematics, School of Science, College of Science and Technology, University of Rwanda, Kigali, Rwanda
1

School of Medicine, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda
2

How to cite this paper: Ntaganda, J.M., Abstract

Minani, F., Banzi, W., Mpinganzima, L.,
Niyobuhungiro, J., Gahutu, J.B., Rutagan- Mathematical modelling of glucose-insulin system is very important in medi-
da, E., Kambutse, I. and Dusabejambo, V. cine as a necessary tool to understand the homeostatic control of human
(2018) Simplified Mathematical Model of
body. It can also be used to design clinical trials and in the evaluation of the
Glucose-Insulin System. American Journal
of Computational Mathematics, 8, 233-244. diabetes prevention. In the last three decades so much work has been done in
https://doi.org/10.4236/ajcm.2018.83019 this direction. One of the most notable models is the global six compart-
ment-mathematical model with 22 ordinary differential equations due to
Received: August 30, 2018
Accepted: September 15, 2018
John Thomas Sorensen. This paper proposes a more simplified three com-
Published: September 18, 2018 partment-mathematical model with only 6 ordinary differential equations by
introducing a tissue compartment comprising kidney, gut, brain and peri-
Copyright © 2018 by authors and
phery. For model parameter identification, we use inverse problems tech-
Scientific Research Publishing Inc.
This work is licensed under the Creative nique to solve a specific optimal control problem where data are obtained by
Commons Attribution International solving the global model of John Thomas Sorensen. Numerical results show
License (CC BY 4.0). that the proposed model is adaptable to data and can be used to adjust di-
http://creativecommons.org/licenses/by/4.0/
abetes mellitus type I or type II for diabetic patients.
Open Access

Keywords
Glucose, Insulin, Mathematical Model, Parameter, Identification

1. Introduction
It is common knowledge that lifestyle factors largely influence our health. These
factors are diet, physical activity, smoking and psychological stress. The lifestyle
changes have the influence on metabolism of some systems of human body
including glucose-insulin system, for example disordered glucoregulation. Therefore

DOI: 10.4236/ajcm.2018.83019 Sep. 18, 2018 233 American Journal of Computational Mathematics
J. M. Ntaganda et al.

two variables that have a bearing on glucose homeostasis are affected, those are:
pancreas beta cell response to glucose and sensitivity of body to insulin. The key
organs that control blood glucose are pancreas and liver. The key hormones are
insulin and glucagon. Large-scale clinical trials have demonstrated the benefits
of tight control of glucose-insulin system, minimizing disease complications and
improving quality of life [1]. Human body needs to maintain glucose
concentration level in a narrow range. According to the World Health
Organization or the International Diabetes Federation the cut-offs for fasting blood
sugars, hypoglycemia is below 70 mg/dl and hyperglycemia is more than 126
mg/dl. The upper normal limit is 200mg/dl. Many researches are motivated by
the large population of diabetes patients in the world and the big health expenses
to study the glucose-insulin endocrine metabolic regulatory system [2] [3] [4] [5]
[6]. They are interested in what cause the dysfunctions of the system [7], how to
detect the onset of either type of diabetes including the so called prediabetes [8]
[9] [10] [11], and eventually provide more reasonable, more effective, more
efficient and cost-effective treatments to diabetes. For example, diabetes mellitus
is a metabolic disorder caused by insufficient insulin production in islet cells in
the pancreas or by tissue resistance against secreted insulin, which leads to
excessive glucose concentration in the blood.
Since the 1960s, mathematical models have been developed to describe
glucose-insulin dynamics [7]. Starting from the model proposed by Bolie in 1961
[12] mathematical modeling of glucose-insulin interaction in normal body has
been studied. Some of these mathematical models are interested in analysing the
glucose disappearance and insulin sensitivity during an intravenous glucose
tolerance test [13] and capture of plasma glucose and insulin dynamics during,
as well as after, periods of mild-to-moderate exercise [14]. Others focus on
overestimation of glucose effectiveness and the underestimation of insulin
sensitivity [15], capture absorption, distribution and disposal dynamics [16].
More detailed compartmental models have been proposed by Cobelli et al. [17],
Hovorka et al. [18] and Sorensen [19]. Most of these models have been used for
diabetes mellitus modeling by adjusting the model for type I or type II diabetic
patients. The mathematical properties of the dynamic systems of glucose and
insulin have been analyzed by some authors [2] [10] and [20]. The use of
ordinary and partial differential equations to model biological systems cannot
capture the rich variety of dynamics observed in natural systems for attempting
to better our understanding of more and more complicated phenomena. One of
the ways of dealing with these complexities is to include delays in the
mathematical models. In 2012, a mathematical model has been developed to
capture the integral impact of physical activity to glucose and insulin [21]. The
existing global mathematical model due to John Thomas Sorensen [19] is
complicated in term of computational complexity as it has many equations and
parameters. The objective of this paper is therefore to propose a simplified
mathematical model which is adaptable to observed data and can be used to

DOI: 10.4236/ajcm.2018.83019 234 American Journal of Computational Mathematics

 J. M. Ntaganda et al.

adjust diabetes mellitus. Furthermore, we propose three compartment-mathematical

model with only six odes by introducing a tissue compartment instead of a six
compartment-mathematical model with 22 ordinary differential equations from
[19]. The mathematical modeling follows a mathematical design where model
equations are obtained by considering Adolf Fick's law [22] and Boyle-Mariotte's
law [23]. For validation of the designed model, we use data obtained by solving
the global mathematical model from [19].
The rest of the paper is organised as follows. In Section 2, we set mathematical
model equations. The Section 3 deals with qualitative study. Estimation of model
parameters is presented in Section 4 while Section 5 focuses on concluding
remarks.

2. Model Equations
The Sorensen model [19] deals with the behavior of different organs in a healthy
human body by explicitly defining an individual compartment for each organ.
The model also takes into account the individual effects of glucagon hormones
and insulin on glucose metabolic rate in the different human body organ
compartments. There are different methods that can be used to find mathematical
model of glucose-insulin by physiologic compartmentalization. From the
mathematical mode developed by Sorensen [19], we take into account the work
described in [24] and [25]. The current work modified the Sorensen model to
consider the tissue compartment as set of brain, kidney, gut and periphery. This
means that the blood from those elements passes through the tissue
compartment to flow into the heart and lungs compartment. Figure 1 shows the
exchange between physiologic compartments.

Figure 1. Diagram of mathematical model with three main physiologic compartments: Heart, liver and tissues. Arrows
connecting the physiologic compartments represent the direction of blood flow. In general, subscripts distinguish
physiologic compartments.

DOI: 10.4236/ajcm.2018.83019 235 American Journal of Computational Mathematics

J. M. Ntaganda et al.

The metabolic sources and sinks in the glucose-insulin mathematical model

are from the physiologic processes that happen at a constant rate. The
mathematical nomenclature is defined in Table 1 and corresponds to the
symbols used in the glucose insulin mathematical as shown in Figure 1. Since
pancreatic insulin is released into the portal system which perfuses the liver, and
since separate compartments have not been included in the model for vessel
blood volumes, pancreatic insulin release appears as a source term in the liver
insulin compartment.
Taking into account the exchanges illustrated in Figure 1, mass balances for
the glucose insulin model result in a set of 6 simultaneous ordinary differential
equations which are nonlinear as a result of the metabolic source and sink rates.
 G dGH ( t )
= QLG GL ( t ) + γ TG ( GT ( t ) ) − QHG GH ( t ) − RHG ,
α
VH
 dt
V G dGL ( t ) = Q G G t − Q G G t + R G ,
 L A H ( ) L L( ) L
dt
 dG ( t )
VTG T
= QPG ( GH ( t ) − GT ( t ) ) − RTG ,
 dt
 (1)
V I dI H ( t ) =QLI I L ( t ) + γ TI ( IT ( t ) ) − QHI I H ( t ) ,
β

 H dt
 dI ( t )
VLI L = QAI I H ( t ) − QLI I L ( t ) + RPIR − RLI ,
 dt
 I dI T ( t )
VT = QPI ( I H ( t ) − IT ( t ) ) − RTI .
 dt

Table 1. Nomenclature of mathematical model.

Variable Description
V Volume (L)
G Glucose concentration (mg/dL)
I Insulin concentration (mU/dL)
Q Vascular blood flow (dL/min)
Subscript Description
H Heart and Lungs
L Liver
T Tissues
A Hepatic Artery
PIR Peripheral insulin release
Superscript Description
G Glucose
I Insulin
Constant to be estimated Description
R Metabolic source
or sink rate (mg/min or mU/min)
γ Vascular blood flow rate (dL/min)
α Parameter
β Parameter

DOI: 10.4236/ajcm.2018.83019 236 American Journal of Computational Mathematics

 J. M. Ntaganda et al.

3. Model Qualitative Study

Let X e = ( GHe , I He , GLe , I Le , GTe , ITe )′ be the steady state vector where X' denotes the
transpose of X. In order to analyse the steady state, we need to solve the
following system:

 L L T T ( )
Q G G e + γ G G e α − Q G G e =
H H RHG ,
QAG GHe − QLG GLe = − RLG ,

 e e RTG
GH − GT = QPG
,

 (2)
( )
β
QLI I Le + γ TI ITe − QHI I He = 0,
 I e I e
QA I H − QL I L = RLI − RPIR ,

I e − I e = RTI
.

H T
QPI

Note that the first three equations and the last three equations of (2) form the
glucose model and insulin model respectively. From the glucose model we get
GHe and GLe as functions of GTe

RTG 1   RG  
GHe = GTe + G
and GLe = G  − RLG + QAG  GTe + TG   , (3)
QP QL   QP  

and the glucose model becomes

 L L T T ( )
Q G G e + γ G G e α − Q G G e =
H H RHG ,
 RG
G=
H
e
GTe + TG ,
 QP

 e 1  G G e RTG  
GL =  − RL + Q A  GT +  .
 QLG   QPG  

In the same way, from the insulin model we get I He and I Le as functions of
ITe

RTI 1  I  e RTI  
I He =ITe + I
and I e
L = Q I + I  + RPIR − RLI  ,
I  A T
(4)
QP QL   QP  

and the insulin model can be rewritten as follows

 L L T T ( )
Q I I e + γ I I e β − Q I I e =
H H 0,
 RI
 I He= ITe + TI ,
 QP

 e 1  I  e RTI  I

 I L Q I QA  IT + Q I  + RPIR − RL  .
=
  
L  P  
∂G ∂I
Let  G =
∂X
( )
X e and  I =
∂X
( )
X e be Jacobian matrices of glucose

model and insulin model respectively where all derivatives are evaluated at the
equilibrium point X e . After some algebraic calculations we get

DOI: 10.4236/ajcm.2018.83019 237 American Journal of Computational Mathematics

J. M. Ntaganda et al.

( ) ( )
α −1 β −1
 −Q G Q G αγ G G e   −Q I QLI βγ TI ITe 
 H L T T   H 

G = Q G
−QL G
0  and  = Q I −Q I 0  . (5)
 AG G
 I
 AI L
I

Q
 P 0 −Q P   PQ 0 −Q P 
   
The behaviour of the mathematical model (1) near the steady state can be
analysed by the nature of the real parts of the eigenvalues of matrices  G and
 I . The proof of the theorem below will use the following proposition due to
Routh-Hurwitz [26].
Proposition 1. Let a1 , a2 and a3 be positive real numbers. The roots of the
polynomial
λ 3 + a1λ 2 + a2 λ + a3 =
0

have negative real parts when a1a2 > a3 .

Theorem 2.
The system (1) is asymptotically stable if the following conditions are satisfied:
1)

αγ TG ( GTe )
α −1
< QHG − QAG , (6)

2)
QLG G
αγ TG ( GTe ) ( )
α −1
< QH − QAG + QHG + QLG , (7)
QPG

3)
1
αγ TG ( GTe ) ( ) (Q )
α −1
<  2Q G Q G Q G − Q G Q G Q G + Q G 2
G
+ QLG
(
Q Q + Q   )
G G P L H
G L A H H P

 P P H
(8)
( )(
+ QLG QPG + QHG − QAG + QPG QHG + QLG  , ) ( )( )
2 2



4)

βγ TI ( ITe )
β −1
< QHI − QAI , (9)

5)
QLI
βγ TI ( ITe ) ( )
β −1
< QHI − QAI + QHI + QLI , (10)
QPI

6)
1
βγ TI ( ITe ) ( ) (Q )
β −1
<  2Q I Q I Q I − Q I Q I Q I + Q I 2 I
+ QLI
(
QPI QPI + QHI   )
P L H L A H H P

  (11)
( )(
+ QLI QPI + QHI − QAI + QPI QHI + QLI  . ) ( )( )
2 2



Proof.
The system (1) is asymptotically stable if and only if  G and  I are
stability matrix; that is, every eigenvalue of  G and  I has a negative real
part. The characteristic equation associated to  G is PG ( λ ) = 0 given by

DOI: 10.4236/ajcm.2018.83019 238 American Journal of Computational Mathematics

 J. M. Ntaganda et al.

αγ TG ( GTe )
α −1
−QHG − λ QLG
QAG −QLG − λ 0 0.
=
QPG 0 −QPG − λ

That is

λ 3 + ( QHG + QLG + QPG ) λ 2

 (
+ QPG QHG + QLG − αγ TG GTe ( ) ) + Q (Q
α −1 G
L
G
H − QAG  λ
 ) (12)

(
+ QPG QLG QHG − QAG − αγ TG (G ) ) =
e α −1
T 0.

Similarly PI ( λ ) = 0 is equivalent to

λ 3 + ( QHI + QLI + QPI ) λ 2

 (
+ QPI QHI + QLI − αγ TI ITe ( ) ) + Q (Q
α −1 I
L
I
H − QAI  λ
 ) (13)

( (I ) ) =
e α−
1
+ QPI QLI QHI − QAI − αγ TI T 0.

Using Proposition 1, we need to verify the following requirements: all the

coefficients of (12) are positive and the product of coefficients of second and
third terms of (12) is strictly greater than its fourth term.
Indeed, since all vascular blood flow rates are positive, then the relation
Q + QLG + QPG > 0 is obvious. The next requirement is
G
H

(
QPG QLG QHG − QAG − αγ TG GTe ( )
α −1
) > 0,
which after some calculations is equivalent to

αγ TG ( GTe )
α −1
< QHG − QAG .

Similarly, the requirement

(
QPG QHG + QLG − αγ TG GTe ( )
α −1
) + Q (Q
G
L
G
H )
− QAG > 0,

is equivalent to
QLG G
αγ TG ( GTe ) ( )
α −1
< QH − QAG + QHG + QLG .
QPG

The last requirement

(
Q G Q G + Q G − αγ G G e
 P H L T T ( ) ) + Q (Q
α −1 G
L
G
H  )(
− QAG  QHG + QLG + QPG )
(14)
(
> QPG QLG QHG − QAG − αγ TG (G ) ) ,
e α −1
T

yields after calculations (8).

The requirements (9), (10) and (11) are obtained in a similar way by
considering the insulin model.

DOI: 10.4236/ajcm.2018.83019 239 American Journal of Computational Mathematics

J. M. Ntaganda et al.

4. Model Parameter Identification

The nonlinear system (1) can be represented in the following compact form
X ( t ) = f ( X ( t ) , µ ) , (15)

where µ is the vector of parameters to be estimated. That is

µ = ( γ TG , α , RHG , β , γ TI , RLG , RTG , RTI )′ .

The mathematical model requires parameter identification which can be

carried out by setting the following optimal control problem. We determine the
control µ such that the cost functional

∫0 qG ( GH ( t ) − GH ) ( )
tf 2 2
(µ )
J= obs
+ qI I H ( t ) − I Hobs dt , (16)

is minimized under the restriction of the model Equation (15). The positive
scalar coefficients qG and qI determine how much weight is associated to
each term in the integrand. Superscript “obs” refers to the observed state to
which the system is transferred by the control. In order to obtain the observed
data, we solve the global model of [19]. The variation of glucose and insulin in
heart are plotted in Figure 2.
For computational purposes we discretize the system (15) using N linear
B-splines. Let us consider
N
= {ψ=,jN
j 1, , N , } (17)

a linear B-splines basis functions on the uniform grid

 kT 
Ω N = tk = , k = 0, , N  , (18)
 N 
such that
ψ iN ( tk ) = δ ik ,

where δ ik is Kronecker symbol. Let us introduce the vector space W N whose

Figure 2. Observed data: Glucose (a) and Insulin (b).

DOI: 10.4236/ajcm.2018.83019 240 American Journal of Computational Mathematics

 J. M. Ntaganda et al.

the basis is  N . It follows that dim W N = N and W n ⊂ W n+1 , n =

1, , N . We
assume that functions appearing in the system (15) are continuous on [ 0,T ] .
Let us denote W = C 0 ( 0, T ) and consider the interpolation operator
Π N :W → W N ,
satisfying ∀φ ∈ W
Π N φ ( tk =
) φ ( tk ) , k= 1, , N .
Therefore, in this setting we are looking for the solution X N ∈ W N of the
following discrete problem
=X N ( t ) ( )
X N ( t ) , µ N , such that X N ( 0 ) X 0N ,
f= (19)

where the control is

(γ ) ( ).
8
=µN G,N
T , α N , RHG , N , β N , γ TI , N , RLG , N , RTG , N , RTI , N ∈ W N

The corresponding discrete optimal control problem (16) is to minimize

( q (G ) )h T
N
( tk ) − GHobs ) (
2 2
∑ G
N
H + qI I HN ( tk ) − I Hobs with h = (20)
k =1 N
with respect to (19). In compact form the problem (20) can be rewritten as
follows
N
min
µN
( )
J N µ N = ∑ hYkT RYk
k =1
(21)

subject to

(
 X N ( t ) = f X N ( t ) , µ N ) (22)
 N
 X ( 0 ) = X 0
N

where Yk , k = 1, , N is the following matrix

((G N
H ( tk ) − GHobs ) , ( I HN ( tk ) − I Hobs ) )′ ,
and R is the matrix defined by
q 0
R= G .
 0 qI 

The numerical computations have been carried out using a collection of

MaTlaB routines [27] specifically the built-in function fmincon. Table 2 shows
the estimated parameters of mathematical model (1). Using those parameters we
get numerical solutions shown in Figure 3.

5. Concluding Remarks
Physiological and dynamical conditions for glucose and insulin impose the need
for relatively simple models that should be able to describe as accurately as
possible the mechanical behavior of glucose-insulin system. In this work we have
proposed a three compartmental mathematical model that describes the variation
of glucose and insulin for human being. The modelling technique is used to

DOI: 10.4236/ajcm.2018.83019 241 American Journal of Computational Mathematics

J. M. Ntaganda et al.

Table 2. Estimated model parameters.

Parameter Value

γ G
T 5.1575

α 0.0354

β 1.0422

γ I
T 2.1056

R G
H 9.9966

R G
L 1042.1509

RLI 7.6076

R G
T 40.8085

R I
T 1.0013

Figure 3. Variation of glucose concentration (a) and insulin concentration (b). The
dashed line denotes observed data while solid line is solution of our mathematical model.

provide interesting answers to the question of determining the global

mathematical model with lower number of equations for glucose-insulin system.
Numerical results show that the proposed model is adaptable to data. In fact
Figure 3 shows that adjustment for glucose and insulin trends match observed
data. The proposed mathematical model can also be used to adjust diabetes
mellitus type I or type II for diabetic patients.

Conflicts of Interest
The authors declare no conflicts of interest regarding the publication of this pa-
per.

References
[1] Turner, R.C., Cull, C.A., Frighi, V. and Holman, R.R. (1999) Glycemic Control with
Diet, Sulfonylurea, Metformin, or Insulin in Patients with Type 2 Diabetes Mellitus:
Progressive Requirement for Multiple Therapies (UKPDS 49), UK Prospective Di-
abetes Study (UKPDS) Group. JAMA, 281, 2005-2012.

DOI: 10.4236/ajcm.2018.83019 242 American Journal of Computational Mathematics

 J. M. Ntaganda et al.

https://doi.org/10.1001/jama.281.21.2005
[2] Bennett, D.L. and Gourley, S.A. (2004) Asymptotic Properties of a Delay Differen-
tial Equation Model for the Interaction of Glucose with the Plasma and Interstitial
Insulin. Applied Mathematics and Computation, 151, 189-207.
https://doi.org/10.1016/S0096-3003(03)00332-1
[3] Simon, C. and Brandenberger, G. (2002) Ultradian Oscillations of Insulin Secretion
in Humans. Diabetes, 51, S258-S261. https://doi.org/10.2337/diabetes.51.2007.S258
[4] Sturis, J., Polonsky, K.S., Mosekilde, E. and Van Cauter, E. (1991) Computer-Model
for Mechanisms Underlying Ultradian Oscillations of Insulin and Glucose. Ameri-
can Journal of Physiology, 260, E801-E809.
https://doi.org/10.1152/ajpendo.1991.260.5.E801
[5] Tolic, I.M., Mosekilde, E. and Sturis, J. (2000) Modeling the Insulin-Glucose Feed-
back System: The Significance of Pulsatile Insulin Secretion. Journal of Theoretical
Biology, 207, 361-375. https://doi.org/10.1006/jtbi.2000.2180
[6] Topp, B., Promislow, K., De Vries, G., Miura, R.M. and Finegood, D.T. (2000) A
Model of β-Cell Mass, Insulin, and Glucose Kinetics: Pathways to Diabetes. Journal
of Theoretical Biology, 206, 605-619. https://doi.org/10.1006/jtbi.2000.2150
[7] Bergman, R.N., Finegood, D.T. and Kahn, S.E. (2002) The Evolution of Beta-Cell
Dysfunction and Insulin Resistance in Type 2 Diabetes. European Journal of Clini-
cal Investigation, 32, 35-45. https://doi.org/10.1046/j.1365-2362.32.s3.5.x
[8] Bergman, R.N., Ider, Y.Z., Bowden, C.R. and Cobelli, C. (1979) Quantitative Esti-
mation of Insulin Sensitivity. American Journal of Physiology, 236, E667-E677.
[9] Bergman, R.N. and Cobelli, C. (1980) Minimal Modeling/Partition Analysis and the
Estimation of Insulin Sensitivity. Federation Proceedings, 39, 110-115.
[10] De Gaetano, A. and Arino, O. (2000) Mathematical Modeling of the Intravenous
Glucose Tolerance Test. Journal of Mathematical Biology, 40, 136-168.
https://doi.org/10.1007/s002850050007
[11] Mukhopadhyay, A., De Gaetano, A. and Arino, O. (2004) Modeling the Intravenous
Glucose Tolerance Test: A Global Study for a Single-Distributed-Delay Model. Dis-
crete and Continuous Dynamical Systems Series B, 4, 407-417.
[12] Bolie, V.W. (1961) Coefficients of Normal Blood Glucose Regulation. Journal of
Applied Physiology, 16, 783-788. https://doi.org/10.1152/jappl.1961.16.5.783
[13] Cobelli, C., Pacini, G., Toffolo, G. and Sacca, L. (1986) Estimation of Insulin Sensi-
tivity and Glucose Clearance from Minimal Model: New Insights from Labeled
IVGTT. American Journal of Physiology, 250, E591-598.
[14] Bergman, R.N., Phillips, L.S. and Cobelli, C. (1981) Physiologic Evaluation of Fac-
tors Controlling Glucose Tolerance in Man: Measurement of Insulin Sensitivity and
Beta-Cell Glucose Sensitivity from the Response to Intravenous Glucose. Journal of
Clinical Investigation, 68, 1456-14567. https://doi.org/10.1172/JCI110398
[15] Cobelli, C., Caumo, A. and Omenetto, M. (1999) Minimal Model SG Overestima-
tion and SI Underestimation: Improved Accuracy by a Bayesian Two-Compartment
Model. American Journal of Physiology, 277, E481-488.
[16] Hovorka, R., Shojaee-Moradie, F., Carroll, P.V., Chassin, L.J., Gowrie, I.J., Jackson,
N.C., Tudor, R.S., Umpleby, A.M., Jones, R.H. (2002) Partitioning Glucose Distri-
bution/Transport, Disposal, and Endogenous Production during IVGTT. American
Journal of Physiology-Endocrinology and Metabolism, 282, E992-E1007.
https://doi.org/10.1152/ajpendo.00304.2001
[17] Cobelli, C. and Mari, A. (1983) Validation of Mathematical Models of Complex

DOI: 10.4236/ajcm.2018.83019 243 American Journal of Computational Mathematics

J. M. Ntaganda et al.

Endocrine-Metabolic Systems. A Case Study on a Model of Glucose Regulation.

Medical & Biological Engineering & Computing, 21, 390-399.
https://doi.org/10.1007/BF02442625
[18] Hovorka, R., Canonico, V., Chassin, L.J., Haueter, U., Massi-Benedetti, M., Federici,
M.O., Pieber, T.R., Schaller, H.C., Schaupp, L., Vering, T. and Wilinska, M.E. (2004)
Nonlinear Model Predictive Control of Glucose Concentration in Subjects with
Type 1 Diabetes. Physiological Measurement, 25, 905-920.
https://doi.org/10.1088/0967-3334/25/4/010
[19] Thomas, S.J. (1985) A Physiologic Model of Glucose Metabolism in Man and Its
Use to Design and Assess Improved Insulin Therapies for Diabetes. PhD Thesis,
Massachusetts Institute of Technology, Cambridge.
[20] Drozdov, A. and Khanina, H. (1995) A Model for Ultradian Oscillations of Insulin
and Glucose. Mathematical and Computer Modelling, 22, 23-38.
https://doi.org/10.1016/0895-7177(95)00108-E
[21] Ntaganda, J.M. and Mampassi, B. (2012) Modelling Glucose and Insulin in Diabetic
during Physical Activity. Proceeding of the 4th International Conference, Al Ain,
11-14 March 2012, 331-344.
[22] Fick, A. (1870) Uber die messung des Blutquantums in den Hertzvent rikeln. Sitzber
Physik Med Ges Wurzburg July 9th, 36.
[23] Levine, I.N. (1978) Physical Chemistry. University of Brooklyn, McGraw-Hill, New
York.
[24] Tiran, J., Galle, K.R. and Porte, D. (1975) A Simulation Model of Extracellular Glu-
cose Distribution in the Human Body. Annals of Biomedical Engineering, 3, 34-46.
https://doi.org/10.1007/BF02584487
[25] Guyton, J.R., Foster, R.O., Soeldner, J.S., Tan, M.H., Kahn, C.B., Koncz, L. and
Gleason, R.E. (1978) A Model of Glucose-Insulin Homeostasis in Man That Incor-
porates the Heterogenous Fast Pool Theory of Pancreatic Insulin Release. Diabetes,
27, 1027-1042. https://doi.org/10.2337/diab.27.10.1027
[26] Routh, E.J. (1877) A Treatise on the Stability of a Given State of Motion: Particular-
ly Steady Motion. Macmillan, London.
[27] Higham, D.J. and Higham, N.J. (2000) Matlab Guide. SIAM, Philadelphia.

DOI: 10.4236/ajcm.2018.83019 244 American Journal of Computational Mathematics