APSC 150 Module: Metabolic Rate

Dr. Ezra Kwok

PhD, MD, PEng, CCFP, CCAMA

Professor, Chemical and Biological Engineering

Staff Physician and Surgical Assistant, Mount St. Joseph Hospital
Family Doctor, Vancouver and Richmond
Founding Director, Biomedical Engineering (2005-2010)

Biomedical Engineering

Lecture #1 - Objectives
After this lecture, you should be able to :
Define metabolic rate and basal metabolic rate.
Compare direct calorimetry and indirect calorimetry.
Calculate basal metabolic rate using physiological
data.
Explain the derivation of the Harris-Benedict
equation.

Diabetes Mellitus
Chronic disease
Inability of pancreas to
control blood glucose
Complications:

Finger pricking:
pain
patient compliance

Nephropathy (Kidney diseases)

Retinopathy (Brain diseases)
Neuropathy
Ketoacidosis (DKA)

Need Good Control

Courtesy of the University of Pennsylvania Health System

Biomedical Engineering
Case Study :
Modeling and Control of
Diabetes Mellitus

Introduction : Metabolic Rate

Amount of energy liberated (used) from a
living organism per unit of time
Expressed in terms of the rate of heat liberation
during chemical reactions

Measure of Energy:
1 calorie = amount of energy to raise 1g of water by
1 degree Celsius
1 Cal = 1 kcal = 1000 calories = 4.2 kilojoules

Factors that affect metabolic rate

1. Exercise

Exercise produces an increase in metabolic rate

2. Ingestion of food

Increase metabolic rate

The specific dynamic action of protein

3. Emotional state
4. Environmental temperature

20-30 C have stable metabolic rate

< 20 C or >30C , metabolic rate is increased

5. Other factors (sleep, sex, etc.)

Metabolic Rate in Various Conditions

Basal Metabolic Rate (BMR)
Minimum energy required to sustain life
(Measured when Waking State with No Food & No Movement)

Resting Metabolic Rate (RMR)

Combination of
Basal Metabolism (waking state)
Sleeping Metabolism
Arousal Metabolism

Exercise Metabolic Rate

Metabolism during Exercise + RMR

Basal Metabolic Rate(BMR)

Metabolic rate during basal conditions
Minimum level of energy required for life
Useful for diagnosing the diseases:
Hyperthyroidism, hypothyroidism

Metabolic Rate
Measurement of the metabolic rate
Direct calorimetry
Indirect calorimetry

Caloric value / thermal equivalent of food

Oxygen consumption / thermal equivalent of oxygen 1 L
Respiratory quotient CO2 / O2

How Do You Measure Metabolic Rate?

Method #2)
Indirect Calorimetry

Substrate (CHO or Fat) + O2 + Energy (ATP)

CO2 + H2O + Energy (ATP) + Heat

Method #1)
Direct Calorimetry

Method #1)

Direct Calorimetry
Total Energy from Metabolism...
~40% ATP
~60% Heat

So
if you measure your bodys heat production,
you can estimate energy production!

Direct Calorimetry
-How does it work?-

Heat
Exchanger

Insulated
Chamber

Water flow in the heat exchanger

The difference in the temperature of water entering and
leaving the chamber reflects the persons heat production.

Direct
Calorimetry

By D. Gordon E. Robertson (Own work) [CC-BY-SA-3.0

(http://creativecommons.org/licenses/by-sa/3.0) or GFDL
(http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons
http://upload.wikimedia.org/wikipedia/commons/1/15/Snellen_human_calorimeter%2C
_uOttawa.jpg

Direct Calorimetry
-Problems

Expensive
Not applicable in most activities
Highly impractical for large-scale studies
Very few pieces of equipment in nation

SoMethod #2

Method #2)

Indirect Calorimetry
Complete Combustion of Food
IS
Achieved at the Expense of O2 Molecules.

So
if you measure your oxygen uptake,
you can estimate energy production!

Indirect Calorimetry

http://upload.wikimedia.org/wikipedia/commons/b/b0/Indirect_calorimetry_laborat
ory_with_canopy_hood.jpg
By Cosmed (Own work) [CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia
Commons

Linear Least Square Fitting

Definition : any data point
in a given model is
expressed linearly in terms
of the unknown parameters

Y Value
10
8

http://en.wikipedia.org/wiki/Linear_least_squ
ares_(mathematics)

4
2
0

10

15

1. Data summarization
2. Understand the tendency
in the given system
3. Prediction of unobserved
values

Linear Least Square Fitting

Y Value
7
6

Assume that the line that

best fits the data is

4, 6

2, 5

3, 4

Squared deviation of a point

is ;

1, 3

2
1

Orange line : deviation

0
0

real
data

linear
approximation

Best approximation = minimizes the sum of squared deviations

Linear Least Square Fitting

When the partial derivatives of function S(a,b) with respect to a, b are 0 : minimum

Do some calculations to get a and b

Linear Least Square Fitting

Y Value
7

4, 6

y = 0.8x + 2.5

Now we know that the

straight line that best
fits the data is

2, 5

3, 4

1, 3

This method is used

when deriving HarrisBenedict Equation.

1
0
0

The Original Harris-Benedict Equation

Men:
BMR [kcal/day] = 66.4730 + (13.7516 x weight in kg)
+ (5.0033 x height in cm) (6.7550 x age in years)

Women:
BMR [kcal/day] = 655.0955 + (9.5634 x weight in kg)
+ (1.8496 x height in cm) (4.6756 x age in years)

The Original Harris-Benedict Equation:

The Revised Harris-Benedict Equation

Men:
BMR [kcal/day] = 88.362 + (13.397 x weight in kg)
+ (4.799 x height in cm) - (5.677 x age in years)

Women:
BMR [kcal/day] = 447.593 + (9.247 x weight in kg)
+ (3.098 x height in cm) - (4.330 x age in years)

The Original Harris-Benedict Equation:

Activity Factor
Little to no exercise
Light exercise (13 days per
week)
Moderate exercise (35 days
per week)
Heavy exercise (67 days per
week)

Daily calories needed = BMR x 1.2

Daily calories needed = BMR x 1.375

Daily calories needed = BMR x 1.55

Daily calories needed = BMR x 1.725

Very heavy exercise (twice per

Daily calories needed = BMR x 1.9
day, extra heavy workouts)

Tutorial 1
Basic Regression Practice
And
Metabolic Rate Calculation

Lecture #2 - Objectives
After this lecture, you should be able to :
Explain the difference in body composition between
men and women.

Understand energy balance and do simple

calculations.

Calculate energy intake using given data.

Typical body composition

Man

Woman

Reference Male

Reference Female

Reference Female(2)

Male vs Female

Male

Female

(note differences in fat and muscle content)

What is Essential Fat?

Consists of fat stored in major organs, muscles,
and central nervous system

Important for childbearing and hormone-related

functions
Required for normal physiological
functioning: reducing essential fat below some
minimal amount can impair overall health.
Extremes in dieting (and exercise) can reduce
essential fat stores

Sex Differences in Essential Fat

Essential Fat(%)

15

12

10

Men
5

Women

Men

Women
Of this amount, 5 to 9% is called
sex-specific, reserve storage fat
contained in breast and genital regions,
lower body subcutaneous fat, and
intramuscular depots

Sex Differences in Storage Fat

Storage fat accumulates mainly in adipose tissues.
This fat depot includes visceral fatty tissues and
adipose tissue deposited beneath the skins surface
called subcutaneous fat
Storage Fat(%)

20
15

12

15
Men

10

Women

5
0
Men

Women

The common anatomic sites for subcutaneous fat include the triceps,
subscapula, iliac ,mid- abdomen, and upper thigh

Body Composition
-Bioelectrical Impedance Low voltage electricity is
sent through your body.
Fat is a very poor conductor
of electricity, a lot of fat will
impede the current more so
than a lot of lean tissue.
By measuring the resistance
to the current, the machine
estimates the percent body
fat

+/- 3% error
Dependant upon
Abstain from eating and drinking
within 4 hours of the test
Avoid exercising within 12 hours
of the test
Void (urinate) completely prior to
testing
Do not drink alcohol within 48
hours of the test
Avoid taking diuretics prior to
testing unless instructed by your
physician

Body Composition
-Bioelectrical ImpedanceBenefits
Requires little or no
technical knowledge of the
operator or the client
Testing itself takes less than
a minute
The unit can be easily
transported from place to
place
Requires only an electrical
outlet and the machine itself

Disadvantages
This method has a higher
standard error range than
most people desire
Tends to consistently
overestimate lean people
and underestimate obese
people
Accuracy dependant on
variables which may be hard
to control

American Council on Exercise

Classification

Women
(% fat)

Men
(% fat)

Essential Fat

10-12%

2-4%

Athletes

14-20%

6-13%

Fitness

21-24%

14-17%

Acceptable

25-31%

18-25%

Obese

32% plus

25% plus

Energy Balance
Energy input = Energy output
heat
Food

heat

heat
ATP

Cellular function

heat

Metabolism

Food

Heat

Energy Balance
Energy balance = energy intake energy expenditure

Energy intake
influence of diet composition
caloric density

CHO = 4 kcal g-1

protein = 4 kcal g-1
fat = 9 kcal g-1
ethanol = 7 kcal g-1

Calculate % Intake from Fast-Food Fat

Breakfast - McDonald's
Sausage McMuffin w/Egg
1% Milk - 8 oz
Hash Brown Potatoes
Lunch - Burger King
Bacon Double Cheeseburger
French Fries - regular
Chocolate Shake - 10 oz
Snack
Snicker's Candy Bar
Dinner - Taco Bell
Two Tacos
Combination Burrito
Pepsi - 24 oz
TOTAL (40% of intake from fat)

Energy
(kcal)
517
110
125

Fat
(g)
33
2
7

510
227
374

31
13
11

280

13

372
404
288
3,207

16
16
0
142

Tutorial 2
Basal Metabolic Rate 1

APSC 150 Module: Diabetes Mellitus

Dr. Ezra Kwok

PhD, MD, PEng, CCFP, CCAMA

Professor, Chemical and Biological Engineering

Staff Physician and Surgical Assistant, Mount St. Joseph Hospital
Family Doctor, Vancouver and Richmond
Founding Director, Biomedical Engineering (2005-2010)

Acknowledgements
A number of slides are taken from the
public domain.

Dr. Omid Vahidi

Dr. Rasha Salama
Jennifer J. Darrow
Canadian Diabetes Association

An Overview of
Diabetes Mellitus

Lecture #3 - Objectives
After this lecture, you should be able to :
Understand glucose metabolism.
Explain briefly about the mechanism of insulin.
Define diabetes mellitus and compare type 1 and
type 2.

Glucose Metabolism
Pancreas
Located behind the
stomach
Endocrine portion is in
the islets of Langerhans

Alpha cells: glucagon

Beta cells: Insulin
Delta cells: Somatostatin
F cells: Pancreatic
polypeptide

Picture is taken from: http://www.nature.com

Glucose: the preferred nutrient

Carbohydrates are the preferred
source of energy for the body.
Final products of carbohydrate
digestion
in the digestive tract are
monosaccharides (glucose [80%],
fructose and galactose)
Much of fructose and all galactose
are converted to glucose in the liver
and released back into the blood.
health.howstuffworks.com/diabetes1.htm
Glucose is a large molecule that must
be broken down into a form of
energy usable by the cell (ATP).

Structure of ATP : Adenosine Triphosphate

High-energy
bonds

phosphate group

A
adenosine

Catabolism : Molecule Breakdown

Glucose is broken down into many
molecules of ATP
(higher # if O2 present)

Glucose (C6H12O6 )

When bond is broken, energy is released

to do cellular work

Adenosine Diphosphate(ADP)

Glucose Metabolism
The process of glucose
metabolism involves
1) glycolysis,
2) the citric acid cycle (Krebs cycle)
3) electron transport.
1-cytoplasm;
2, 3-mitochondria

Complete reaction:
C6H12O6 + 6O2 >>
6CO2 + 6H2O
Net gain = 36 ATP
http://www.medaille.edu/vmacer/120_graphic_05cellresp.jpg

Glucose Metabolism

By Mikael Hggstrm [Public domain], via Wikimedia Commons

Glucose Metabolism(cont.)
Only 40% of the energy released through catabolism of
glucose is captured in ATP.
The remaining 60% escapes as heat that warms the
interior of the cells and the surrounding tissues.
If cells have inadequate amounts of glucose to
catabolize, they immediately shift to the catabolism of
fats for energy.
In starvation, proteins are used for energy after
carbohydrate and fats are depleted.

Alternative Catabolic Pathways

Glycogen

Triglycerides

Proteins

used first

Fatty Acids

cytoplasm

then...

Glycerol

Glucose

Pyruvic
acid

Acetyl-CoA
mitochondrion

Citric
Acid
Cycle

Electron Transport
ATP Production

Amino Acids

Glucose Metabolism Summary

Catabolism
Energy production from fuel sources
Glucose
Supplied in food as exogenous source
Produced endogenously
Gluconeogenesis: in the liver and kidney
Glycogenolysis: in the liver and muscles
Glucose absorption
Insulin binding
Cell signaling
Glucose transporter (GLUT)
Glycogenesis Glycolysis
Glucose homeostasis
Insulin and glucagon hormones
Glycogenolysis and gluconeogenesis
Picture is taken from: http://weightlossfrogs.blogspot.com
http://en.wikipedia.org/wiki/File:Insulin_glucose_metabolism.jpg

Regulation of Nutrients
Insulin regulates ;
1. Uptake of nutrients into the cells
2. Storage of nutrients not being used
3. Conversion of one nutrient type to another

Metabolic Efficiency : Glucose

Cells rely on insulin for efficient absorption of
glucose from the blood (except brain cells)
Insulin also enhances ATP production
Without insulin not enough glucose is supplied to
tissues for energy metabolism

A Simplified View of the Mechanism of Insulin

SIMPLY PUT, insulin can be

thought of as the funnel that
allows glucose to pass through
the receptors into cells.

S= SUGAR (glucose)

www.umassmed.edu/diabeteshandbook
/chap01.htm

http://upload.wikimedia.org/wikipedia/commons/c/ce/Insulin_glucose_metabolism_ZP.svg

Mechanism of Action of Insulin*

The insulin receptor is a

combination of 4
subunits held together by
disulfide linkages: two subunits lying outside the
cell membrane and two
-subunits protruding
into the cell cytoplasm.

* Adapted from a presentation by Ann K. Snyder, 8/16/2000

Mechanism of Insulin
When insulin binds to the
-subunit in target
tissues, the -subunits in
turn become activated.

Mechanism of Action of Insulin*

Activation of the -subunits

triggers a series of reactions that
draw the glucose transporter to
the cell membrane.
Cells (liver, muscle, adipose, but
not brain) are now able to
increase their uptake of glucose.
(w/in seconds after insulin binds
with its membrane)
The cell membrane also becomes
more permeable to many amino
acids.

Mechanism of Action of Insulin

Ref: http://www.diabetes.org/

(animated)

What is Diabetes Mellitus

Human pancreas
Islets of
Longerhans

Cell resistance
against insulin

Diabetes Gk
: Excessive urine
Mellitus Latin
: Honey

Beta cell
Muscle fiber

Blood
vessel

Insulin

Glucose

Picture is taken from: http://www.wereyouwondering.com

Lack or insufficiency
of insulin production

Significance
Diabetes mellitus
Diabetes is the seventh leading cause of death (at the United States)
350 millions of the people worldwide (about 5%) have diabetes
It has positive
rate of growing
Diabetes Population
United States
diabetes growth rate
11.4%
11.0%

Non-Diabetic, 95%

10.6%
10.2%
9.8%
Mar-2008

Jun-2008

Sep-2008

Dec-2008

Mar-2009

Jun-2009

Diabetic, 5%

Type II Diabetes

Comprises 90-95% of diabetic population

Very few studies are performed on modeling and

blood sugar control of type II diabetes despite its large
population

Type II Diabetes
Type I
10%

Type II
90%

Sep-2009

Type I Diabetes

- not hereditary
- but a genetic
disease

Pictures are taken from: http://www.nlm.nih.gov & http://ww.medicalook.com

The body immune system

destroys the beta cells
Juvenile disease

Not enough insulin for

glucose absorption

Type I Diabetes
An autoimmune disease leading to the
destruction of beta cells
No more insulin production
A classic research topic for process control
(more on Lecture 5)
Why classic control problem?
Insulin

Glucose

Type II Diabetes
Multiple abnormalities
Peripheral tissues
Insulin resistance
Glucose resistance

Overall rate Low

peripheral g
lucose uptake

Glucose

Impaired insulin sup

pression

Pancreatic insulin release rate

peak
Insulin Early
resistance
Glucose resistance

Gluconeogenesis
Glycogenolysis

Liver
Impaired insulin stimulation of glucose uptake
Impaired glucose stimulation of glucose uptake
Impaired insulin suppression of glucose
production
Pancreas
Blunted or no early peak of insulin production
Impaired overall insulin production rate
Picture
Picture
is taken
is taken
from:
from:
http://www.diabetespharmacist.com
http://www.pawelmazur.org el_agency.webs.com

Insulin

Glucose abs
orption

Glucose

Impaired insulin sti

mulation
Impaired glucose sti
mulation

Healthy subject

Diabetic subject

Time

Type II Diabetes
Insufficient production of insulin
Cell resistance against glucose and insulin
Different body organ dysfunction such as liver,
pancreas and peripheral tissues
About 90% to 95% of all diabetic patients!!!

Type II Diabetes

hereditary

Mathematical Modeling
Introduction

Compartmental modeling approach

Circulatory system
Circulatory system

Motivation

Sorensen model

(Simplified) body
Selecting a suitable healthy human
model

Brain

Brain

A detailed compartmental model proposed by

Sorensen is selected
Heart

Objectives

Eliminating the weaknesses of the model

Lung

Heart & lungs

Glucose absorption in the gastrointestinal tract

A three compartmental model is added
Methodology

Intravenous
injection

Incretins hormonal effect on insulin release

A one compartmental model is added
Effects of the incretins on insulin releaseLiver
is added

Results

Selecting relevant parameters for parameter

estimation

Pancreas
Liver

GI tract

Stomach

Future works

Conclusion

Intestine
Based on abnormalities of type II diabetes
some
parameters of the Sorensen model have been
selected for parameter estimation
Kidney

Establishing an optimization problem using

available clinical data
The objective is to minimizePeripheral
the model
tissues
discrepancy from clinical data

Picture is taken from: http://healthkp.com/blood-circulation-problems-tingling-in-the-hands-and-feet/

Kidney

Peripheral
tissues

Blood samples

Type I & Type II Diabetes

Know the difference
Type I Diabetes

"Blausen 0308 Diabetes Type1" by BruceBlaus - Own work. Licensed under Creative Commons Attribution
3.0 via Wikimedia Commons http://commons.wikimedia.org/wiki/File:Blausen_0308_Diabetes_Type1.png#mediaviewer/File:Blausen_
0308_Diabetes_Type1.png

Type II Diabetes

"Blausen 0309 Diabetes Type2" by BruceBlaus - Own work. Licensed under Creative
Commons Attribution 3.0 via Wikimedia Commons http://commons.wikimedia.org/wiki/File:Blausen_0309_Diabetes_Type2.png#media
viewer/File:Blausen_0309_Diabetes_Type2.png

Tutorial 3
Diabetes Mellitus 1

Lecture #4 - Objectives
After this lecture, you should be able to :

Evaluate medical conditions of diabetes patients.

Understand how to prevent and treat diabetes.
Explain what carbohydrate counting is and its usage.

Calculate proper insulin injection ratio.

Diabetes:
Symptoms

"Main symptoms of diabetes" by Mikael

Hggstrm.When using this image in external
works, it may be cited as follows:Hggstrm,
Mikael. "Medical gallery of Mikael Hggstrm
2014". Wikiversity Journal of Medicine 1 (2).
DOI:10.15347/wjm/2014.008. ISSN 20018762.
- See above. All used images are in public
domain.. Licensed under Public domain via
Wikimedia Commons http://commons.wikimedia.org/wiki/File:Mai
n_symptoms_of_diabetes.png#mediaviewer/
File:Main_symptoms_of_diabetes.png

Diabetes: Symptoms(2)

Glycosuria
Excessive glucose in blood
drags water out through
the kidney resulting in
POLYURIA: huge urine
output >>> decreased
blood volume and
dehydration.

health.howstuffworks.com/ diabetes1.htm

Dehydration stimulates
hypothalamic thirst
centers, causing
POLYDIPSIA: excessive
thirst.

Other Side Effects of Polyuria

The dehydration resulting from polyuria also leads to
dry skin.
During a period of dehydration, blurred vision can be
caused by fluctuations in the amount of glucose and
water in the lenses of the eyes.

http://www.nws.noaa.gov/sec508/htm/low_vision.htm

Polyphagia
polyuria, polydypsia, & polyphagia
= the 3 cardinal signs of diabetes
POLYPHAGIA: excessive hunger and food
consumption, a sign that the person is starving in
the land of plenty. That is, although plenty of
glucose is available, it cannot be used, and the cells
begin to starve.
Without fuel, cells cannot produce energy >> fatigu
e and weight loss.
http://clear.msu.edu:16080/dennie/clipart/

Insulin deficiency >> metabolic use of FAT

A deficiency of insulin will accelerate the
breakdown of the bodys fat reserves for fuel.
Free fatty acids become the main energy
substrate for all tissues except the brain.
Increased lipolysis results in the production of
organic acids called ketones (KETOGENESIS) in the
liver.
Note: Cells in the muscle, liver, and fat need insulin to receive
glucose. However, other cells such as those in the brain, nervous
system, heart, blood vessels and kidneys pick up glucose directly
from the blood without using insulin.

Effects of insulin deficiency on

metabolic use of fat
Excess fat metabolism
leads to an increase in
plasma cholesterol >>>
increased plaque
formation on the walls
of blood vessels.
High fat concentration
Hardening of blood vessels
Heart disease

Other complications of diabetes:

A reduction in blood flow to the
feet can lead to tissue death,
ulceration, infection, and loss of
toes or a major portion of one
or both feet.
Damage to renal blood vessels
can cause severe kidney
problems.(Nephropathy)
Damage to blood vessels of the
retina can also cause blindness.
(Retinopathy)
http://my.diabetovalens.com/infocus/feafeb0404.asp

Diabetic Neuropathy
neurological diseases

Patients with neuropathy lose

their sensation of pain. As a
result, they exert a lot of
pressure at one spot under
the foot when they walk,
building up a callus at that site
without causing discomfort.

The pressure becomes so high

that eventually it causes
breakdown of tissues and
ulceration.
www.thefootclinic.ca/services_diabetic.php

A Typical Neuropathic Ulcer Is

1) painless
2) surrounded by callus

3) associated with good

foot pulses (because the
circulation is normal)
4) at the bottom of the
foot & tips of toes

www.diabetes.usyd.edu.au/foot/Neurop1.html

www.thefootclinic.ca/services_diabetic.php

Blood Glucose
Fasting blood glucose concentration
(person who has not eaten in the past -8 hours)
Normal person:
Diabetic patient:

3.5 to 6.0 mmol/L

> 7.0 mmol/L

Two hours after a meal:

Normal person:
Diabetic patient:

< 10.9 mmol/L

> 11.0 mmol/L

2013

Diagnosis of Diabetes
FPG 7.0 mmol/L
Fasting = no caloric intake for at least 8 hours
or

A1C 6.5% (in adults)

Using a standardized, validated assay, in the absence of factors that affect the
accuracy of the A1C and not for suspected type 1 diabetes
or

2hPG in a 75-g OGTT 11.1 mmol/L

or

Random PG 11.1 mmol/L

Random= any time of the day, without regard to the interval since the last meal
2hPG = 2-hour plasma glucose; FPG = fasting plasma glucose; OGTT = oral glucose tolerance test; PG = plasma glucose

Note: one test insufficient, at least two required

2013

Diagnosis of Prediabetes*

Test

Result

Prediabetes Category

Fasting Plasma
Glucose
(mmol/L)

6.1 - 6.9

Impaired fasting glucose

(IFG)

7.8 11.0

Impaired glucose tolerance

(IGT)

6.0 - 6.4

Prediabetes

2-hr Plasma Glucose in

a 75-g Oral Glucose
Tolerance Test (mmol/L)
Glycated
Hemoglobin
(A1C) (%)

* Prediabetes = IFG, IGT or A1C 6.0 - 6.4% high risk of developing T2DM

Diabetes: Prevention
Regular physical activity including endurance
exercise and weight training
Moderate diet rich in whole grains, fruits,
vegetables, legumes, fish, and poultry
Modest weight loss
For people with pre-diabetes, lifestyle changes
are more effective than medication in
preventing diabetes

Diabetes: Prevention
Tip 1: Get more physical activity
Tip 2: Get plenty of fiber
Tip 3: Go for whole grains
Tip 4: Lose extra weight
Tip 5: Skip fad diets and just make healthier
choices
By Mayo Clinic

How to measure blood glucose

Glucose Meter
Invasive
-finger pricking(common)
-test strips w/ enzymes

Non-invasive
-optical/electrical approach

SCOUT DS, from VeraLight Inc. (InLight Sol.)

By BruceBlaus. When using this image in external sources it can be cited as: Blausen.com
staff. "Blausen gallery 2014". Wikiversity Journal of Medicine. DOI:10.15347/wjm/2014.010.
ISSN 20018762. (Own work) [CC-BY-3.0 (http://creativecommons.org/licenses/by/3.0)], via
Wikimedia Commons

Glucose Meter-Invasive
Usually enzyme based : e.g. glucose oxidase
A. 1) Glucose in the blood reacts with the
enzyme(glucose oxidase) in the test
strip
2) Reaction results in color change
which is translated into a number
By BruceBlaus. When using this image in
external sources it can be cited as:
Blausen.com staff. "Blausen gallery 2014".
Wikiversity Journal of Medicine.
DOI:10.15347/wjm/2014.010. ISSN
20018762. (Own work) [CC-BY-3.0
(http://creativecommons.org/licenses/by/
3.0)], via Wikimedia Commons

B. 1) Reaction with enzyme produces

electric current which is translated into
a number

Glucose Meter-Invasive
Glucose

Gluconic Acid

Glucose Dehydrogenase(Enzyme)
2 ferrocyanide
diffusion

2 ferricyanide
e-

Glucose
Meter
e-

CGMS
(Continuous Glucose Monitoring System)
FDA approved CGMS & Enzyme-based Implantable

www.Minimed.com

www.dexcom.com

www.abbottdiabetescare.com

MiniMed Paradigm REALTime System

Dexcom SEVEN Plus

Abbott FreeStyle
Navigator

Life span

3 days

7 days

5 days

Canula size

14 mm

13 mm

5 mm

Price

$35

$100

2 hour start-up initialization time

Optical Approaches: Non-Invasive

Measures glucose non-invasively via
NIR spectroscopy
Various components such as sweat, fat,
etc. can interfere with efficacy
On-going studies with patient use
SCOUT DS, from VeraLight Inc. (InLight Sol.)

Sensys GTS
Sensys

Medical Systems

Diabetes: Treatment
Keep blood sugar levels within safe limits through
diet, exercise, and, if needed, medication
Monitor blood sugar levels with a home test
Lose weight if overweight

How to keep blood sugar levels

Carbohydrate Counting

What is Carbohydrate Counting?

Estimating the carbohydrate(CHO)
content of food so that you can adjust
your insulin dose to match the amount
of carbohydrate you want to eat.

Advantages of Carbohydrate Counting

Getting the best of from your insulin regimen

Good glycaemic control
Freedom to eat when you want to
Freedom to eat as little or as much as you wish
Freedom to eat traditionally forbidden food without
feeling guilty

Carbohydrate Foods
STARCHY FOODS

SUGARS
http://upload.wikime
dia.org/wikipedia/co
mmons/3/3c/Sucre_
blanc_cassonade_co
mplet_rapadura.jpg

Bread

Sugar

Potato

Glucose

Rice

Sugary drinks

Pasta

Sweets, chocolate

Breakfast cereals

Sweet puddings

Biscuits and other

Fruit

Flour products

Milk

Yoghurt

Estimating CHO

Weighing food
Measuring using cups & spoons
Food labels
Recipes that list CHO content
CHO Counting tables/books

http://upload.wikimedia.org/wikipedia/commons/2/2b/Nutritionfacts.png
By Rorybowman (here) [Public domain], via Wikimedia Commons

Quick or Slow Acting Carbohydrate

Low Glycemic Index

Foods sweetened with

All meats
All dairy products

nuts, olives, cheese, pita chips, fried pork rinds

Alcohol

Special K, All Bran, Fiber One, regular oatmeal

Snacks

thin stands, whole wheat pasta, bean threads

Cereals

barley, bulgar, kasha

Pasta

whole rye, pumpernickel, whole wheat pita

Grains

All except the High GI vegetables above

red wine

Misc

olives, eggs, peanut butter (no sugar)

Foods containing sugar

all cereals except those on the Low GI List below

Snacks

thick, large pasta shapes

Cereals

rice, rice products, millet, corn, corn products

Pasta

all white breads, all white flour products, corn breads

Grains

potatoes, corn, carrots, beets, turnips, parsnips

Breads

bananas, melons, pineapple, raisins

Vegetables

honey, molasses, & corn syrup.

Fruits

Breads

all except the High GI fruits above

Vegetables

(no sugars)

Fruits

saccharin, aspartame, fructose

High Glycemic Index

Potato chips, corn chips, popcorn, rice cakes, pretzels

Alcohol

beer, liqueurs, all liquor except red wine

Rise in blood sugar is influenced by:

The biggest effect is
from the amount of
CHO eaten
Speed of digestion &
absorption of CHO you
eat

Basal insulin
Lantus
or
Levemir

Establish a Ratio
If you checked your Pre breakfast sugar e.g. 7 mmols
Had 30 gm CHO at breakfast
And had 6u insulin
2 hour post meal blood sugar was 6.2 mmols
Ratio = 2 units insulin per 10gm CHO
Pre-breakfast
Blood sugar
Ratio

7 mmols

Post-meal
30gm CHO + 6u insulin
2u insulin/10gm CHO

6.2 mmols

Is my Ratio correct
If your Pre-meal blood glucose was 7 mmols
and you ate 30gm CHO
and had 6u Insulin
2-hour Post meal blood glucose 12 mmols
Ratio not high enough
Try 3u insulin per 10gm CHO
Pre-breakfast
Blood sugar

7 mmols

Ratio

Post-meal
30gm CHO + 6u insulin

12 mmols

Not high enough

TRY

3u insulin/10gm CHO

Is my Ratio correct
If your Pre-meal blood glucose was 7 mmols
and you ate 30gm CHO
and had 6u Insulin
2 hour Post meal blood glucose 2.3 mmols
Ratio too high
Try 1u insulin per 10gm CHO
Pre-breakfast
Blood sugar
Ratio

7 mmols

Post-meal
30gm CHO + 6u insulin

2.3 mmols

Too high
TRY

1u insulin/10gm CHO

Tutorial 4
Diabetes Mellitus 2

APSC 150 Module: Control of Diabetes Mellitus

Dr. Ezra Kwok

PhD, MD, PEng, CCFP, CCAMA

Professor, Chemical and Biological Engineering

Staff Physician and Surgical Assistant, Mount St. Joseph Hospital
Family Doctor, Vancouver and Richmond
Founding Director, Biomedical Engineering (2005-2010)

Acknowledgements

A number of slides are taken from the

following textbook and the public domain.

Process Dynamics and Control by Seborg,

Edgar, and Mellichamp

Introduction to
Process Control
Control of Diabetes Mellitus

Lecture #5 - Objectives
After this lecture, you should be able to :
Define process control variable, manipulated variable,
disturbance variable, set-point change, and
disturbance change.
Compare feedback control and feedforward control.
Apply the concept of process control to human body.
(e.g. type 1 diabetes.)

Chapter 1

What is Process Control?

Chapter 1

Chapter 1

Control Terminology
Process or Controlled variables - these are the variables
which quantify the performance or quality of the final
product, which are also called output variables.
Manipulated variables - these input variables are
adjusted dynamically to keep the controlled variables at
their set-points.
Disturbance variables - these are also called "load"
variables and represent input variables that can cause the
controlled variables to deviate from their respective set
points.

Temperature
PV:

Temperature

MV:

Coolant flow

Load: Ambient temperature

Process fluid fluctuation
Coolant temperature

Chapter 1

Control Terminology(2)
Set-point change - implementing a change in the
operating conditions. The set-point signal is changed and
the manipulated variable is adjusted appropriately to
achieve the new operating conditions. Also called
servomechanism (or "servo") control.
Disturbance change - the process transient behavior
when a disturbance enters, also called regulatory control
or load change. A control system should be able to
return each controlled variable back to its set-point.

Illustrative Example: Blending system

Notation:
w1, w2 and w are mass flow rates
x1, x2 and x are mass fractions of component A

 Assumptions:
1. w1 is constant

Chapter 1

2. x2 = constant = 1 (stream 2 is pure A)

3. Perfect mixing in the tank

Control Objective:
Keep x at a desired value (or set point) xsp, despite variations in x1(t).
Flow rate w2 can be adjusted for this purpose.

Terminology:
Process or Controlled variable (or output variable): x
Manipulated variable (or input variable): w2
Disturbance variable (or load variable): x1

Design Question. What value of w2 is required to have

x xSP ?
Overall balance:

Chapter 1

0 w1 w2 w

(1-1)

Component A balance:
w1x1 w2 x2 wx 0

(1-2)

(The overbars denote nominal steady-state design values.)

At the design conditions, x xSP . Substitute Eq. 1-2, x xSP

and x2 1 , then solve Eq. 1-2 for w2 :
xSP x1
w2 w1
1 xSP

(1-3)

 Equation 1-3 is the design equation for the blending

system.
If our assumptions are correct, then this value of w2 will keep x
at xSP . But what if conditions change?
Control Question. Suppose that the inlet concentration x1
changes with time. How can we ensure that x remains at or
near the set point xSP?
As a specific example, if x1 x1 and w2 w2 , then x > xSP.

Some Possible Control Strategies:

Method 1. Measure x and adjust w2.
Intuitively, if x is too high, we should reduce w2;
Manual control vs. automatic control
Proportional feedback control law,

w2 t w2 Kc xSP x t

(1-4)

1. where Kc is called the controller gain.

2. w2(t) and x(t) denote variables that change with time t.

3. The change in the flow rate, w2 t w2 , is proportional to
the deviation from the set point, xSP x(t).

Chapter 1

Feedback Control
Measure the process variable (PV)
Compare with the target value (Setpoint)
The error between the set point and PV is used to
make adjustment to the MV and minimize the error.

Method 2. Measure x1 and adjust w2.

Chapter 1

Thus, if x1 is greater than x1 , we would decrease w2 so that

w2 w2 ;
One approach: Consider Eq. (1-3) and replace x1 and w2 with
x1(t) and w2(t) to get a control law:

w2 t w1

xSP x1 t
1 xSP

(1-5)

Chapter 1

Feedforward Control
The Load (or disturbance signal) is measured.
MV is adjusted ahead of time based on the load
before the load can affect the system.

Process

Because Eq. (1-3) applies only at steady state, it is not clear how effective the contr
ol law in equation (1-5) will be for transient conditions.

Method 3. Measure x1 and x, adjust w2.

This approach is a combination of Methods 1 and 2.
Load x1

Set point

Process

Process
variable
x

Chapter 1

Classification of Control Strategies

Control Strategies for the Blending System
Method

Measured
Variable

Manipulated
Variable

Category

w2

FBa

x1

w2

FF

x1 and x

w2

FF/FB

Design change

Feedback Control
Distinguishing feature : measure the process variable

Advantages :
Corrective action is taken regardless of the source of the disturbance.
Reduces sensitivity of the controlled variable to disturbances and changes
in the process (shown later).

Disadvantages :
No corrective action occurs until after the disturbance has upset the
process, that is, until after x differs from xsp.
Very oscillatory responses, or even instability

Feedforward Control
Distinguishing feature : measure a disturbance variable

Chapter 1

Advantage:
Correct for disturbance before it upsets the process.

Disadvantage:
Must be able to measure the disturbance.
No corrective action for unmeasured disturbances.

Application
Applying feedback control and feedforward control
to blood glucose level of type 1 diabetes. (next few
slides)
Basic structure :

Feedback control of blood glucose

Insulin

Glucose

Feedforward control of blood glucose

Disturbances

Feedforward
Control

Carbohydrate Counting

Insulin

Glucose

Feedback & Feedforward

Disturbances
Feedforward
Control

Carbohydrate Counting

Insulin

Glucose

Tutorial 5
Process Control for
Diabetes Mellitus