CONTROL ALGORITHM DEVELOPMENT

FOR ARTIFICIAL PANCREAS FOR TYPE-

1 DIABETES PATIENT
Glucose-Insulin system inside a normal human body
Glucose-Insulin system inside a diabetic patient
body
 Bergman Minimal Model (BMM)
Nonlinear model

Glucose dynamics
G (t ) = Blood glucose concentration
dG }
Disturbance
I (t ) = Blood insulin concentartion
= - p1 (G (t ) - Gb ) - X (t )G (t ) + D(t ) X (t ) = Insulin concentartion in remote compartment.
dt
D(t ) = Disturbance in terms of carbohydrate (glucose) intake.
dX
= - p2 X (t ) + p3 ( I (t ) - I b ) p1 = Insulin independent rate constant of glucose uptake by tissue.
dt p2 = Rate of decrease of glucose uptake by tissue
Insulin kinetics p3 = Insulin dependent rate of increase of glucose uptake by tissue
dI (t ) Gb = Basal preinjection blood glucose level.
= - n( I (t ) - I b ) + g (G (t ) - h) + t Ib = Basal preinjection plasma insulin level.
dt
g (G (t ) - h) + t = Internal regulatory function that formulates
insulin secretion in body.
For T1DM patient,g (G (t ) - h) t is neglected.
+
Two Compartment Model

p1 = k1 + k5
p2 = k3
p3 = k2 ( k4 + k6 )
Disturbance Term
 Shimoda Insulin Model
The Artificial Pancreas proposed comprises of a subcutaneous insulin infusion.

There is a delay in the transfer of insulin from subcutaneous tissue to plasma.

The Shinoda model accounts for this by using a 2 compartment insulin kinetics model
 Shimoda Model Equations

dx1 (t ) x1 = Subcutaneous insulin mass at the administration site.

= -k21 x1 (t ) + U s (t )
dt x2 = Insulin mass proximal to plasma.
dx2 (t ) U s = Subcutaneous insulin lispro administration routes.
= k21 x1 (t ) - (kd + ka ) x2 (t )
dt U i = Intravenous insulin lispro administration routes.
dI (t ) ka
= x2 (t ) - ke I (t ) + U i (t ) Vd = Plasma distribution volume.
dt Vd
PHARMACOKINETIC PARAMETER
k21 = Rate of transfer from peripheral to central compartment.
ka = Rate of Absorption.
Ui = 0; for a subcutaneous insulin kd = Rate of Distribution.
infusion pump system ke = Rate of Elimination.
 Pharmacokinetic Parameters
Thestudy of kinetics of absorption, distribution, metabolism & excretion (ADME) of drugs after
administration .
Plasma Volume Distribution

Absorption Rate Constant

Ka =

Elimination Rate Constant

Ke =
Consolidated Model

dG
= - p1 (G (t ) - Gb) - X (t )G (t ) + D(t )
dt
dX
= - p2 X (t ) + p3 ( I (t ) - I b )
dt
dx1 (t )
= - k21 x1 (t ) + U s (t )
dt
dx2 (t )
= k21 x1 (t ) - ( kd + ka ) x2 (t )
dt
dI (t ) ka
= x2 (t ) - ke I (t )
dt Vd
 OGTT (Oral Glucose Tolerance Test)
In this test, the subject fast for an 8 to 12 hour period.
After which the blood glucose and insulin concentrations are measured which is known as
fasting blood glucose value.
Then the subject ingest glucose in a liquid solution orally.
After this ingestion, you take new measurements for a three hour period after every 15
minutes.
The amount of glucose in the liquid is typically 75 g.
Data Collected: Plasma Glucose concentration: G(t)
Plasma Insulin concentration: I(t)
C-peptide
Parameter Estimation
 Parameter Estimation for p1,p2,p3
Estimation of parameters p1, p 2, p 3 of the Glucose kinetics Model

dG
Let =F
dt
F = - p1* ( G (t ) - Gb ) - X (t )* G (t )
p1* Gb - F
X (t ) = - p1*
G (t )
-1 dF F * p1* Gb - F
- 2 ( F + p1 G ) = p 2
*
- p1* + p 3*
I ( t ) - Ib

G dt G G (t )
dG
= F ; G (0) = G 0
dt
dF F
= ( F - p1* Gb ) p1* Gb - p1* p 2* ( G - Gb ) - p 3* G
I ( t ) - Ib
; F (0) = p1 ( Gb - G0 )
dt G
Calculating Ka & Ke
Cp ( t ) = Ae -( a t ) -( b t )
+ Be

Ka =
Alpha
Ke =
 Comparison of Observer and MINMOD estimation

MINMOD Estimation of Insulin Action Observer Estimation of Insulin Action

Parameter estimation of Shimoda
Insulin kinetic model
Known parameter or states:I (t ), K a , K e , Vd
*
Unknown parameter or states (*):x (t ) 2

dI (t ) ka *
= x2 (t ) - ke I (t )
dt Vd
Vd dI (t )
x (t ) =
*
2 + K e I (t )
K a dt
 * * *
Unknown parameter or states:x (t ), k , k 1 21 d

Known parameter or states: x2 (t )

From shimoda insulin kinetic model we know that,
dx2 (t ) * * *
= K 21 x1 (t ) - ( K d + K a ) x2 (t )
dt
* 1 dx2 (t ) *
x1 (t ) = * + ( K d + K a ) x2 (t ) (1)
K 21 dt
Differentiating equation (1) on both side,
* 2
1 d x2 (t ) * dx2 (t )
x&1 (t ) = * 2 + ( K d + K a ) (2)
K 21 dt dt
From Shimoda insulin kinetic model
We know that,
dx1* (t ) * *
= - K 21 x1 (t ) + U s (t) (3)
dt
dx1* (t )
Substituting in (3) to equation (2), we get,
dt
* * 1 d 2
x2 (t ) * dx2 (t )
- K 21 x1 (t ) + U s (t ) = * 2 + ( K d + K a ) (4)
K 21 dt dt
dx2 (t )
Let M = , and rearranging equation (4)
dt
M& = - K 21
*
M - ( K a + K d* ) K 21
*
x2 (t ) - ( K d* + K a ) M + U s (t ) K 21
*
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