NATIONAL QUALIFICATIONS CURRICULUM SUPPORT
Human Biology
Autoimmune Disorders
Case Study on Diabetes
[HIGHER]
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Acknowledgement
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© Learning and Teaching Scotland 2011
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Contents
Background
4
Markers of the disease
19
Solutions
26
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CASE STUDY ON DIABETES
Case study on diabetes
Background
This case study describes the effect of type 1 diabetes on John, a student.
1.
John is a 16-year-old student who was diagnosed with type 1 diabetes at
the age of 5. Until recently the disease has been relatively well
controlled, but now that he is older his parents have less influence on
his daily lifestyle as he strives to be more independent. On a personal
basis, he is quite resentful of the daily commitment necessary to control
the disease.
As a result of neglecting to control his condition, he was recently
admitted to A&E at Gartnavel Hospital with the following symptoms:
generally unwell, very confused and drowsy with a headache and
blurred vision
2.
Dr McBride examined John on his arrival at A&E.
His observations included:
signs of dehydration, dry mucous membranes, skin elastic and wrinkled,
sunken eyeballs, low blood pressure, fast pulse , deep and fast breathing,
and breath smelled of acetone
Dr McBride immediately instructed a nurse to organise blood and urine
tests to be sent to the hospital laboratory for analysis.
3.
Helen, the laboratory technician, carried out tests on blood and urine
samples from John and got the following results:
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CASE STUDY ON DIABETES
Blood tests
John’s results
Normal range of a
healthy person
35
3.3–6.5
7.05
7.3–7.5
Urea
16
2.5–7.5
Sodium (mmol dm –3 )
152
135–145
12
24–35
John’s results
Normal result for a
healthy person
+++ ve
– ve
++ ve
– ve
+
– ve
Glucose (mmol dm –3 )
pH
Hydrogen carbonate
(mmol dm –3 )
Urine tests
Glucose dipstick
Ketone bodies
Protein dipstick
John’s blood and urine results were immediately sent back to Dr McBride.
Based on this information John was given an intravenous drip containing a
combination of salt solution and insulin (4 units of fast -acting insulin per
hour).
The presence of protein in John’s urine reflected a urinary tract infection.
Once the microorganism responsible for the infection had been identified, he
was also prescribed antibiotics.
It was very important to monitor John’s blood sugar level every hour.
Within 4–6 hours John was beginning to make some improvement. As his
blood results returned to normal, the salt solution and insulin were altered
accordingly. This treatment continued for 24 h ours. After 48 hours, the
visible signs of dehydration and ketoacidosis had disappeared.
Task 1
What is ketoacidosis?
Use any available textbooks to find out about this condition .
AUTOIMMUNE DISORDERS (H, HUMAN BIOLOGY)
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CASE STUDY ON DIABETES
When John was completely back to normal, he was discharged.
This may appear to be the end of the story, with a relatively good ending, but
there are still some issues to consider.
Group discussion
What day-to-day problems does John face?
Do the problems of type 1 diabetes change with age?
What social hurdles might John have to face?
What may have caused John to lose control of his condition and end up in
hospital?
What could John do to ensure that he doesn’t end up back in hospital?
What would have happened if John had not been treated so quickly by Dr
McBride?
The good news was that John was successfully treated on this occasion , but
he was quite shaken by the ordeal and made a personal decision to avoid a
recurrence of the event. John is a bright student and after careful
consideration, he came to the conclusion that since he was faced with the
major problem of being type 1 diabetic, he should at least be well informed,
so he decided to find out more about the actual disease, its consequences and
how to treat it.
Revision
In small groups of three or four students create a mind map to include all
relevant details based on all they currently know.The following article may
be a useful reference:
A case of diabetes, Biological Sciences Review, September 2008, p34–37
John is of course familiar with the overall general symptoms and basic
chemistry of type 1 diabetes but decided that it was perhaps time to research
the subject further. He has a good logical mind and particularly enjoys
science at school. He has no definite plans for his future at this stage but is
keen to achieve the grades required for a university course. He is also
naturally curious about why he is afflicted by diabetes. What factors could be
involved? How does the disease work? What is known about the disease?
What lines of research are being carried out?
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CASE STUDY ON DIABETES
There were lots of unanswered questions and John wanted to find out the
answers. He decided it was time to take positive steps to find out more.
Using the school library and the internet he f ound the following references:
1.
Target Diabetes: a comprehensive and user friendly booklet produced
by and available from the Association of the British Pharmaceutical
Industry.
www.abpi.org.uk.
Alternatively, a link to their website:
http://www.abpischools.org.uk/page/resource/age/subject/topic.cfm?age
=Age Range 14-16&subject=Biology
2.
Diabetes UK: a detailed website that provides support information on
all aspects of the disease.
www.diabetes.org.uk
3.
Juvenile Diabetes Research Foundation: mainly supports research into
type 1 diabetes.
www.jdrf.org.uk
4.
Insulin Dependent Diabetes Trust: a charity for people with insulin dependent diabetes and their families/carers .
www.iddinternational.org
John found himself focusing on the following points and questions:
 Type 1 diabetes is an example of an autoimmune disease. What does this
mean?
 What is the immune response?
 What are antigens?
 What are antibodies?
 What are lymphocytes?
 What are autoantibodies?
The following link explains what autoimmune diseases are:
http://www.labtestsonline.org.uk/understanding/conditions/autoimmune.html
AUTOIMMUNE DISORDERS (H, HUMAN BIOLOGY)
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CASE STUDY ON DIABETES
John had come across some of these terms in biology lessons on the immune
system, but at this stage he was rather confused about the connection with
diabetes and so it was time to do some more searching.
A simplified description of these terms can be found on the following
website: http://kidshealth.org/parent/general/body_basics/immunehtml .
John’s understanding was:
In a normal situation, immunity involves:
 the detection of antigens that are foreign to the body
 the recognition of antigens by different cells, which will respond to them
 the production of antibodies by Beta lymphocytes, which will lock onto
the antigens but not actually destroy them
 the destruction of the antigens by T lymphocytes
When the immune system is unable to distinguish between self and non-self
proteins, one or more autoantibodies may be produced . Autoantibodies are a
group of antibodies (immune proteins) that target specific tissues or organs of
the body by mistake. This may cause inflammation and damage, and result in
an autoimmune disorder.
John was reasonably content with his general understanding of autoimmunity
but he could still not quite work out the link to Type 1 diabetes and so his
research continued. He went on to find that:
 in many situations autoantibody production is thought to be due to a
genetic disposition, ie this could explain why some individuals are more
likely to suffer from Type 1 diabetes compared to others
 this genetic disposition may also be combined with an environmental
trigger, eg viral infection,
 resulting in autoimmunity
 based on the genetic link, some families have a higher incidence of Type 1
diabetes
 the type of autoimmune disorder that occurs depends on the system , organ
or tissue that is targeted by the autoantibodies .
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CASE STUDY ON DIABETES
A picture was beginning to develop in John’s mind; his knowledge of type 1
diabetes was sufficient to guess that the target organ in this case must be the
insulin-producing cells of the pancreas.
Figure 1 This image shows (a)different types of cell found in the pancreas and(b)
the position of the pancreas in the human body
John found out that:
 In type 1 diabetes the insulin-secreting beta cells of the islets of
Langerhans are selectively destroyed by an autoimmune process.
Interestingly, the other islet cells can function normally.
 Type 1 diabetes was first considered an autoimmune disease 40 years ago
(1970s).
AUTOIMMUNE DISORDERS (H, HUMAN BIOLOGY)
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CASE STUDY ON DIABETES
 The cause of beta cell destruction was unknown for many years but a
strong link between certain immune recognition molecules and the
presence of certain alleles (ie the genetic link) was found.
 In 1974 immunofluorescence of frozen pancreatic cells showed the
existence of islet cell antibodies (ICA) in diabetic patients.
 At the same time, there was found to be a direct relationship between
certain antigens and diabetes.
 The idea that ICAs could be present years before the development of
diabetes led to research into the identification of specific antigens .
 In the 1980s two main ICAs were identified: glutamic acid carboxylase
(GAD) and IA2 (a protein similar to tyrosine phosphatase autoantibodies).
 This discovery led to the idea that the identification and measurement of
these antibody markers could identify individuals who were at risk of
developing type 1 diabetes.
The more John read about the science behind his disease, the more he wanted
to find out about it. Surely, if so much knowledge was available it should be
relatively simple to halt type 1 diabetes or even prevent it from developing.
He found himself accessing and reading scientific journals and b ecame aware
of how complex the whole subject actually is (eg A comprehensive guide to
antibody and T-cell responses in type 1 diabetes by S.M Lieberman and T.P.
Di Lorenzo, Tissue Antigens2003:62 359-377 Blackwell Munksgaard,
Denmark
John was beginning to realise that this could perhaps be an ideal area to study
at university and he obviously had a personal interest in the topic. At this
point he paused to consider the prospect of becoming involved in a clinical
trial. He was well aware that if such trials did not take place, prevention and
possible treatment of the disease would be adversely affected.
Figure 2 illustrates the type of work carried out during a clinical trial.
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CASE STUDY ON DIABETES
He contacted the Scottish Diabetes Research Network to find out more. They
were keen to tell John what about their work and showed him the results of a
typical trial.
The Table 1 shows the clinical data for blood samples taken from patients
with type 1 diabetes and healthy non-diabetic control subjects.
AUTOIMMUNE DISORDERS (H, HUMAN BIOLOGY)
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CASE STUDY ON DIABETES
Table 1
T cell
respo
nse to
beta
cell
antige
n by
interf
erongamm
a
Subject
Age
(years)
Gender
HLADRB1alleles*
Duration
of type 1
diabetes
GAD
autoantibody
IA2
autoantibody
P1
19
F
40413
4
POSITIVE
POSITIVE
+
P2
25
F
0401 1301
4
POSITIVE
POSITIVE
+
P3
35
F
0301 0401
1
NEGATIVE
NEGATIVE
+
+
12
P4
21
F
0301 0404
7
POSITIVE
NOT
TESTED
P5
19
F
0301 0404
3
POSITIVE
POSITIVE
+
P6
22
M
0401 0401
3
POSITIVE
POSITIVE
+
+
P7
32
F
0408 13
6
POSITIVE
NOT
TESTED
P8
40
M
1301 X
8
POSITIVE
POSITIVE
+
P9
36
F
0301 0404
2
NEGATIVE
NEGATIVE
+
P10
38
F
0301 0401
1
POSITIVE
NEGATIVE
+
NEGATIVE
NOT
TESTED
+
P11
38
F
P12
39
P13
24
P14
T cell
response
to bêta
cell
antigen
by
interleuki
n-17
0101 0401
4
M
0301 08
4
POSITIVE
NEGATIVE
+
M
0301 0401
5
NEGATIVE
POSITIVE
+
20
F
0101 0301
20
POSITIVE
POSITIVE
+
P15
24
M
0301 X
11
POSITIVE
NEGATIVE
+
P16
33
M
0301 1302
4
POSITIVE
POSITIVE
+
P17
20
M
0301 0301
5
POSITIVE
POSITIVE
+
+
P18
25
M
0401 07
12
NEGATIVE
NEGATIVE
+
+
P19
23
M
ND
10
NEGATIVE
NEGATIVE
+
+
P20
35
M
0301 0401
8
POSITIVE
POSITIVE
+
+
P21
29
M
0101 0408
12
NEGATIVE
NEGATIVE
+
+
P22
23
M
0301 15
10
POSITIVE
POSITIVE
+
+
P23
23
F
07
8
NEGATIVE
NEGATIVE
+
+
P24
33
F
ND
8
POSITIVE
NEGATIVE
+
+
P25
20
M
0301 X
4
POSITIVE
POSITIVE
+
+
P26
20
M
0301 0401
7
NEGATIVE
POSITIVE
+
+
P27
39
F
0301 0401
2
POSITIVE
NEGATIVE
+
+
P28
22
M
0101 0301
4
POSITIVE
POSITIVE
+
+
P29
36
M
0301 0401
4
POSITIVE
NEGATIVE
+
P30
20
M
ND
4
POSITIVE
POSITIVE
+
P31
34
F
0301 0401
6
POSITIVE
POSITIVE
+
P32
25
M
0701 0901
4
POSITIVE
NEGATIVE
+
P33
27
F
0101 0401
8
NEGATIVE
POSITIVE
+
X
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CASE STUDY ON DIABETES
P34
22
M
0301 0701
7
POSITIVE
NEGATIVE
+
P35
37
M
0401 X
7
POSITIVE
NEGATIVE
+
P36
41
M
ND
11
NEGATIVE
NEGATIVE
+
P37
26
M
0401 0701
6
POSITIVE
POSITIVE
+
P38
28
F
0701 X
8
POSITIVE
NEGATIVE
+
P39
28
M
0401 X
10
POSITIVE
POSITIVE
+
P40
31
M
0401 12
10
NEGATIVE
POSITIVE
+
P41
20
M
0401 X
8
POSITIVE
NEGATIVE
+
P42
38
M
0401 X
6
POSITIVE
POSITIVE
+
+
+
P43
43
M
0301 0401
2
POSITIVE
NOT
TESTED
P44
18
M
0101 0401
4
POSITIVE
NOT TESTES
P45
18
M
0301 07
4
POSITIVE
NOT
TESTED
NOT
TESTED
NOT
TESTED
NOT
TESTED
NOT
TESTED
NOT
TESTED
NOT
TESTED
NOT
TESTED
+
P46
37
M
0101 1303
8
P47
29
F
0301 0404
8
P48
26
F
ND
4
POSITIVE
P49
33
M
0401 0701
0
POSITIVE
P50
27
M
0401 15
4
POSITIVE
C1
37
F
0401 15
N/A
NEGATIVE
NEGATIVE
+
C2
27
F
0101 1401
N/A
NEGATIVE
NEGATIVE
+
C3
34
F
11 1302
N/A
NEGATIVE
NEGATIVE
+
C4
48
M
0101 1301
N/A
NEGATIVE
NEGATIVE
+
C5
31
F
0403 0407
N/A
NEGATIVE
NEGATIVE
+
C6
37
M
0401 1301
N/A
NEGATIVE
NEGATIVE
+
C7
32
M
15 X
N/A
NEGATIVE
NEGATIVE
+
C8
22
F
0404 1401
N/A
NEGATIVE
NEGATIVE
C9
23
F
0301 1302
N/A
NEGATIVE
NEGATIVE
C10
25
M
11 1301
N/A
NEGATIVE
NEGATIVE
C11
46
M
0101 0404
N/A
NEGATIVE
NEGATIVE
C12
29
F
0301 12
N/A
NEGATIVE
NEGATIVE
C13
24
F
11 16
N/A
NEGATIVE
NEGATIVE
C14
31
M
0101 0407
N/A
NEGATIVE
NEGATIVE
C15
33
F
0401 0701
N/A
NEGATIVE
NEGATIVE
C16
26
F
ND
N/A
NEGATIVE
NEGATIVE
C17
26
F
15 1303
N/A
NEGATIVE
NEGATIVE
C18
24
M
ND
N/A
NEGATIVE
NEGATIVE
C19
25
M
0101 1302
N/A
NEGATIVE
NEGATIVE
C20
40
F
04
0301
N/A
NEGATIVE
NEGATIVE
C21
26
F
04
0301
N/A
NEGATIVE
NEGATIVE
C22
30
F
04
0301
N/A
NEGATIVE
NEGATIVE
C23
35
F
04
0301
N/A
NEGATIVE
NEGATIVE
C24
25
F
04
0301
N/A
NEGATIVE
NEGATIVE
AUTOIMMUNE DISORDERS (H, HUMAN BIOLOGY)
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+
+
+
+
+
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CASE STUDY ON DIABETES
C25
20
M
04
0301
N/A
NEGATIVE
NEGATIVE
C26
40
F
04
0301
N/A
NEGATIVE
NEGATIVE
C27
40
F
04
0301
N/A
NEGATIVE
NEGATIVE
C28
40
F
0401 X
N/A
NEGATIVE
NEGATIVE
C29
40
F
0401 X
N/A
NEGATIVE
NEGATIVE
C30
35
F
N/A
NEGATIVE
NEGATIVE
04
0301
*HLA genes- The HLA (human leukocyte antigen) region is a section of a chromosome that
contains several genes that are involved in the immune system.These genes make proteins that
are important for the immune system to distinguish between its own cells and an infectious
agent, such as a bacteria or virus. When this system fails, the immune cells attack other cells of
the body (such as pancreas cells) in a process called an autoimmune reaction.
There are at least two genes in the HLA region that account for 40 to 50 percent of the diabetes
risk that people inherit from their parents.
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CASE STUDY ON DIABETES
Task 2
Use the raw data in Table 1 to construct a pie chart to show the number of
patients in the study that were in the following age groups:
<20 years
21–25 years
26–30 years
31–40 years
>40 years
Task 3
Use the raw data in Table 1 to construct a bar chart to illustrate the duration
of diabetes in the patients used in this study. Label it Figure (2)
Task 4
A researcher studying the data in Table 1 looked at the figures for the
autoantibodies and drew up Table 2 and Figure 3.
Table 2
GAD autoantibodies
Condition
Total
Present
Absent
Not tested
Diabetic
36
12
2
50
Control
0
30
0
30
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CASE STUDY ON DIABETES
Figure 3
Carefully examine the data in Table 2 and Figure 3, and answer the following
questions.
(a)
What do Table 2 and Figure 3 indicate about the presence or absence of
GAD autoantibodies in diabetic and control subjects?.
(b)
Using some of the other information included in the raw data, create a
new Table (3) to show the levels of IA2 autoantibodies in diabetic and
control subjects.
(c)
Construct a bar chart based on the information in Table 3.
(d)
What does the bar chart indicate?
(e)
Create two similar tables for T-cell responses that produce interferon
gamma or interleukin 17.
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CASE STUDY ON DIABETES
(f)
What do your tables indicate?
(g)
Create and label a bar chart to compare the relative percentages of
interferon gamma and interleukin 17 by T cells.
Research task
T cells produce cytokines such as interferon gamma and interleukin.
Find out what cytokines are and what they do.
What is the significance of their presence in diabetic patients?
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CASE STUDY ON DIABETES
Progression of diabetes can be summarised by the following diagram.
Genetic risk factors
Environmental risk factors
Immune activation
Beta cell injury
Impaired insulin secretion
Glucose intolerance
Disease detected
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CASE STUDY ON DIABETES
Markers of the disease
A great deal of research has focused on the prediction of type 1 diabetes. The
presence of islet tissue specific antibodies i n blood sera from patients with
type 1 diabetes was the first diagnostic of autoimmunity.
The risk of type 1 diabetes is >90% in first-degree relatives of patients who
are positive for at least two autoantibodies whereas it is <20% in relatives
who are positive for only one autoantibody.
Figure 4 shows trends in the levels of different autoantibodies measured over
a child’s life from birth until the development of diabetes.
Figure 4 The production of different autoantibodies in a child who develops ty pe 1
diabetes. From: J.A. Bluestone, K. Herold and G. Eisenbarth, Genetics, pathogenesis
and clinical interventions in type 1 diabetes, Nature, 464, 1293–1300 (DOI
10.1038/08933, April 2010)
Task 5
Using the data in Figure 4:
1.
2.
3.
Describe the trend of the three different types of autoantibodies.
At what age(approximately) did this child develop diabetes?
What changes are evident from the graph between the ages of ~8 and
15?
Significance of the autoantibodies?
John found out that these autoantibodies are markers of autoimmunity and are
not themselves directly destructive to the islets.
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CASE STUDY ON DIABETES
A study group in Finland measured the antibodies in a large sample of
children who had been newly diagnosed with type 1 diabetes and who were
under 15 years of age.The findings of the study showed:
 Nearly 75% of children were GAD positive at diagnosis.
 Just over half the children had anti-insulin antibodies.
 IA2 was the most common antibody and was found in 85.7% of newly
diagnosed children.
 72.6% of the children tested positive for more than one antibody at
diagnosis.
Identifying individuals at risk for type 1 diabetes before substantial islet
injury is thought to offer the best chance of diabetes prevention.
The following images show of different stages of islet cell inv asion by
lymphocytes although, admittedly, in mice.
Figure 5 Different stages of islet cell invasion by lymphocytes in mice. From: J.A.
Bluestone, K. Herold and G. Eisenbarth, Genetics, pathogenesis and clinical
interventions in type 1 diabetes, Nature, 464, 1293–1300, April 2010 (DOI
10.1038/08933).
Research and discussion task
Laboratory-bred mice are extensively used in diabetes research. What are
your own views on this topic? Research, present and discuss the pros and
cons of using mice for this purpose.
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CASE STUDY ON DIABETES
Figure 6 Section of a pancreas showing areas in which all the beta islet (insulin producing) cells have been destroyed.
Discussion point
From what you have learned so far would you expect this individual to have
been diagnosed with type 1 diabetes? Justify your answer
Task 6
Imagine you are a doctor at a diabetic clinic. Consider the following scenario:
Harry, aged 12 years, has type 1 diabetes and his blood tests show that he is
positive for anti-GAD autoantibody. His brother Mark (10 years ) and his
sister Josephine (8 years) are also tested. Mark tested positive and Josephine
tested negative.
Use this information and the data in Table 1 to answer the following
questions:
 Do you now have to tell Mum and Dad that Mark will get type 1 diabetes
in the future?
 Can you reassure them that Josephine will never get it?
 Who is more likely to get type 1 diabetes in the future: Mark or Josephine?
 What other tests could you do on their blood samples to try and be more
certain?
 Consider your own response to these questions and then form groups of
three or four to compare and discuss all views on the matter
AUTOIMMUNE DISORDERS (H, HUMAN BIOLOGY)
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CASE STUDY ON DIABETES
John’s story continued
John had decided that not only would he volunteer for a clinical trial but he
would apply to university to study this topic further. He must look forward
and so he spent some time searching for ideas on how to accomplish th ese
goals.
During his search he discovered an interesting lecture on the prediction and
prevention of type 1 diabetes: http://www.justdiabetesinfo.com/diabetesvideos/predicting-and-preventing-autoimmune-diabetes.html
Although quite demanding in places, he found the lecture of immense interest
and of course it gave a little insight into what university learning was actually
like.
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CASE STUDY ON DIABETES
He also came across a recent newspaper headline that took his attention.
Special infant formula might prevent
childhood diabetes - study
Study suggests a protective effect, but experts say
it's too early for recommendations (10 Nov 2010).
(http:www.reuters.com/article/idUSTRE6A95PU2010111 1)
The report stated that some evidence had been found to suggest that not
giving babies cows’ milk may prevent the development of type 1 diabetes in
children who have inherited the risk of the disease .
John searched the internet for more information and was able to access the
scientific paper based on the study: ‘Dietary intervention in infancy and later
signs of beta cell autoimmunity’
http://www.nejm.org/doi/pdf/10.1056/NEJMoa1004809 )
AUTOIMMUNE DISORDERS (H, HUMAN BIOLOGY)
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CASE STUDY ON DIABETES
The study took place in Finland and concluded that:
Early exposure to complex dietary proteins may increase the risk of b eta-cell
autoimmunity and type 1 diabetes in children with genetic susceptibility.
They tested the hypothesis that supplementing breast milk with highly
hydrolysed milk formula would decrease the cumulative incidence of
diabetes-associated autoantibodies in such children.
The main points of the study found that:
 Accumulating evidence suggests that beta-cell autoimmunity may be
induced early in life.
 The incidence of type 1 diabetes is rising faster than previously among
children, particularly among children younger than 5 years of age.
 Food content in early childhood may modify the risk of type 1 diabetes
later in life.
 A short duration of breast-feeding and early exposure to complex dietary
proteins have been implicated as risk factors for advanced be ta-cell auto
immunity or clinical type 1 diabetes.
 Early nutritional intervention may help to prevent type 1 diabetes and has
been reported to be successful in experimental models of autoimmune
diabetes, although the data are not consistent.
Group task
Aim: To read and extract information from a scientific journal .
Access the original scientific paper for the Finnish study described
http://www.nejm.org/doi/pdf/10.1056/NEJMoa1004809
At least three students per group.
Group 1
Read the background information on page 1901 of the paper and summarise
the main points in your own words.
Group 2
Find out what is meant by hydrolysed milk formula.
How long did the dietary intervention last?
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© Learning and Teaching Scotland 2011
CASE STUDY ON DIABETES
Group 3
What method were used to detect the islet cell antibodies?
What were the cut-off limits for positivity for one or more of the
autoantibodies??
Present the following information as a bar chart:
3.48 RU insulin autoantibodies
5.36 RU GAD autoantibodies
0.43 RU 1A2 autoantibodies
Group 4
What was the median age of the infants at the time casein hydrolysate
formula was introduced?
What was the median age of the infants in the control group?
What percentage of the children in (a) the casein hydrolysate group and (b)
the control group provided at least one blood sample during the follow -up
period for determination of diabetes-associated autoantibodies?
What percentage of the children tested positive for two or more antibodies in
each group?
What conclusion can be made from this data?
Group 5
Read the discussion section on page 1906 of the paper and answer the
following questions.
1.
Select the words in the first paragraph that imply that genes may have
an important role to play in this study.
2.
Which of the autoantibodies showed an observed decrease in positivity?
3.
Why would this be important to young children with a n HLA-defined
disease susceptibility?
Each group should present their findings to the class.
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CASE STUDY ON DIABETES
Solutions
Task 1
Ketoacidosisis is a metabolic disorder associated with a high concentration of
ketone bodies formed by the breakdown of fatty acids and amino acids. It is
common in untreated type 1 diabetes when the liver resorts to breaking down
fats and proteins as a source of energy. It can be fatal if left untreated.
Discussion
Day to day problems:
John would need to monitor his food and drink intake carefully and routinely
measure his blood glucose levels. Insulin injections would be required
depending on the results of his blood glucose. Energy input and output would
be a major factor and he must ensure that he controls his blood glucose level
within the recommended narrow limits of 3.5–6.5 mmol per cubic dm
Problems with age:
If the blood glucose level is higher than normal, over a long period of time, it
can have a damaging effect on the blood vessels. Even a mildly raised
glucose level, which does not cause any symptoms in the short -term, can
affect the blood vessels in the long-term. Some of the following
complications may result although it may be years after diabetes is first
diagnosed
Atheroma (furring or hardening of the arteries) -which can cause problems
such as angina, heart attacks, stroke and poor circulation.
Foot problems – these are due to poor circulation and nerve damage.
Eye problems – which can affect vision, due to damage to the small arteries
of the retina at the back of the eye.
Kidney damage – sometimes develops into kidney failure.
Nerve damage.
Impotence. Again, this is due to poor circulation and nerve damage.
Other rare problems.
The type and severity of long-term complications is very individual. The risk
of developing complications is reduced if other risk factors such as high
blood pressure are controlled.
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CASE STUDY ON DIABETES
Social hurdles:he needs to sample his blood at different times during the day
and inject insulin which may cause some embarrassment/ to him and others
Why did he end up in hospital? He was not always careful about his drinking
habits which sometimes made him forget to take his insulin .
How could he prevent the situation? Better care and control of his blood
glucose levels.
What would have happened to John of he had not been treated quickly ?-when
John arrived at the hospital he was showing typical symptoms of a patient
with Type 1 Diabetes who had failed to take his insulin- ie
HYPERGLYCAEMIC –due to excess excretion of glucose in his urine and
consequent loss of water. This dehydration, along with Acidosis, could
quickly lead to coma a s brain metabolism and function would be impaired.
Task 2-Pie chart
1
2
3
4
5
Key
1 = <20
2 = 21–25
3 = 26–30
4 = 31–40
5 =>40
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CASE STUDY ON DIABETES
Task 3 Bar chart showing the duration of diabetes in the patients used in the
study.
Number of patients
Figure (2)
Task 4
(a)
GAD autoantibodies are only associated with diabetic patients.
(b)
IA2 Autoantibodies
Condition
Diabetic
Control
Table (3)
28
Present
Absent
21
0
18
30
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Non
detectable
11
0
Total
50
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CASE STUDY ON DIABETES
(c)
(d)
IA2 autoantibodies are only detected in diabetic patients.
(e)
Condition
Diabetic
Control
T cell response
Interferon gamma production
Present
Absent
28
22
3
27
Total
50
30
Table (4)
Condition
Diabetic
Control
Table(5)
T cell response
Interleukin 17 production
Present
Absent
34
16
4
25
Total
50
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29
CASE STUDY ON DIABETES
(f)
The cells from diabetic patients are much more likely to produce
Interferon and Interleukin 17 compared to those from control subjects.
Research task – information can be found at:
http://repository.upenn.edu/dissertations/AAI9989622/
http://en.wikipedia.org/wiki/Cytokine
http://www.ncbi.nlm.nih.gov/pubmed/18673007
Task 5: In this particular child,
 GAD autoantibodies- remained at constant negligible levels until ~age 8
when the level increased dramatically but then returned to low, but
detectable levels( ~0.1), prior to the onset of diabetes.
 Microinsulin autoantibodies remained constantly low throughout the study
 ICA512 were extremely low until ~age 8 when ( similar to GAD) the
levels increased from 0-approx 0.1
Research and discussion task – information can be found at:
http://en.wikipedia.org/wiki/Animal_testing
http://www.mrc.ac.uk/Ourresearch/Ethicsresearchguidance/index.htm
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CASE STUDY ON DIABETES
Discussion point: yes, diabetes is likely due to the large area of pancreatic
cells destroyed
Task 6: main points
 The sample size is not sufficient to make any definite conclusions from
this information ie you would only use the results of the test to provide
information on the risk of Mark developing Type 1 Diabetes
 All control patients ie non diabetics were negative for GAD autoantibody
although it was not positive in all the diabetic patients.
 There was no direct correlation between the detection of GAD and the
duration of the diabetes
 There could be no guarantee that Josephine will never get the disease
although there is an increased risk of Mark being diabetic based on this
positive blood test
 Further blood tests should be taken to determine the levels of other
autoantibodies along with genetic screening to provide more informat ion
on the risk of the disease developing.
Solutions to group task
Group 2
 Hydrolysed milk formula -cow's milk proteins that are broken down into
small particles so they're less allergenic than the whole proteins in regular
formulas. Most infants who have a milk allergy can tolerate these
formulas.
 The dietary intervention lasted until 6 months of age.
Group 3
Indirect immunofluorescence was used to detect the islet cell antibodies.
Cut offs for positivity –
2.50 JDF units for islet cell autoantibodies
3.48 RU for insulin autoantibodies
5.36 RU for GAD autoantibodies
0.43 RU for IA2 autoantibodies
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CASE STUDY ON DIABETES
Bar Chart: the relative limits of positivity for different autoantibodies
6
5
relative units
(RU)
4
3
2
1
0
insulin
GAD
autoantibodies
IA2
Group 4
2.6 months
1.1 months
(a)17% and (b) 30%
8% (casein hydrolysate) and 16% (control group)
The control group had a much greater chance of the children having at least
two autoantibodies.
Group 5
1.
HLA genotype conferring an increased risk for type 1 diabetes and a
first-degree relative with type 1 diabetes.
2.
GAD
3.
GAD autoantibodies have been shown to be associated with a low risk
of progression to type 1 diabetes.
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