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Diabetes - Type 1
Although we don’t yet have a cure for Type 1 diabetes, the outcome
for those with type 1 diabetes today is dramatically different from
that of sufferers who lived before 1922. Then, patients died within a
few years of diagnosis. But in 1922 a young Canadian boy became the
first person to receive purified insulin, and his condition improved.
For the next 60 years, insulin was purified from the tissues of cows
and pigs. With the advent of gene cloning, human insulin, produced by
genetically engineered bacteria or yeast, became available. Professor
John Shine was one of the key scientists involved in cloning the gene
for insulin. Yet even with the availability of insulin, having type 1
diabetes will shorten the average person’s life by about 15 years, and
can produce debilitating health problems such as blindness, kidney
damage, heart disease and the need for amputations.
If you would like more information on Type 1 diabetes, click through
the links below.
Diabetes is a group of diseases associated with high blood glucose
(sugar) levels. This indicates a problem with the body’s normal ability
to clear and utilise glucose from the bloodstream.
Type 1 diabetes is marked by severe insulin deficiency. People with
Type 1 diabetes need insulin replacement for survival.
Over a ten year period, a person with Type 1 diabetes may have
14,500 insulin injections and 20,000 finger-prick blood glucose
tests.
When people with diabetes eat carbohydrates (containing glucose),
the glucose cannot be converted into energy for the cell. Instead, the
glucose stays in the blood. This explains why blood glucose levels are
higher in people with diabetes. High levels of blood glucose are
dangerous and can damage many of the body’s systems, especially blood
vessels and nerves.
Type 1 diabetes (reference 1):
• accounts for approximately 10-15% of all diabetes cases in
Australia
• is typically found in younger people, although it can happen at
any age
• is also referred to as ‘juvenile onset’ or ‘insulin dependent’
diabetes
• affects 1 in 700 Australian children.
In mature adults, Type 1 diabetes can present as latent autoimmune
diabetes (LADA) (reference 1). LADA is a slow progressive disease of
our immune system. At presentation, LADA appears to be similar to Type
2 diabetes and can be treated by making lifestyle changes or taking
medication. LADA is actually a slow developing form of Type 1 diabetes
and will eventually require regular insulin injections.
Type 1 diabetes develops when the body’s immune system destroys the
beta cells in the ‘islets’ of the pancreas that produce insulin.
When the immune system treats insulin-producing cells as foreign and
‘not-self, just as it would a virus or bacteria, it is known as an
auto-immune response.
It can take several years to develop Type 1 diabetes.
A combination of genetic and environmental factors is likely to be
involved in the development of the disease, although the exact causes
are unclear. Research is continuing into the causes of Type 1
diabetes.
Type 1 diabetes may be initiated by an environmental insult (a
trigger from the environment such as a virus, diet, stress) in people
who have a genetic susceptibility (have genes which predispose them to
risk of the disease)1. Both the insult and the genes would have to be
present to develop Type 1 diabetes.
When around 75% of the insulin-producing beta-cells have been
destroyed by their own immune system, patients will develop
hyperglycaemia (high blood sugar).
People with Type 1 diabetes produce very little or no insulin.
Without insulin, blood sugar levels rise to dangerously high levels.
Persistent high blood glucose levels can affect your long-term
health.
Type 1 diabetes has no cure and cannot be prevented but it can be
managed.
The incidence of Type 1 and other insulin-treated diabetes in
Australia is increasing at about 3 per cent a year (reference 1). Type
1 diabetes affects over 140, 000 people in Australia.
Australia is in the top 10 countries of those with the highest rates
of Type 1 diabetes in children (reference 2). There were 990 new cases
in 2007 among those aged 0–14 years (reference 1). This represented an
increase of 30% from 2000 to 2007. There was little change in incidence
rates among people aged 15–39 years.
Type 1 diabetes:
• is the most common chronic childhood disease in developed
nations
• is not caused by lifestyle factors.
In children, the onset of Type 1 diabetes may be quite sudden and
the child can have rapid and unplanned weight loss over several weeks
(reference 2). In adults it may appear more slowly and sometimes
symptoms can go unnoticed. This means that a sufferer can go
undiagnosed, and therefore untreated, for a long time.
The symptoms of all types of diabetes are similar. They include:
• frequent urination (especially at night)
• excessive thirst
• hunger or loss of appetite
• unexplained weight loss
• fatigue, nausea and vomiting
• itching skin, thrush or other skin infections
• visual disturbances, such as blurred vision.
However, Type 1 diabetes, especially in children, may present as a
life-threatening illness, Diabetic ketoacidosis (see below).
Diabetes is diagnosed on the basis of a person’s blood glucose
levels and a urine test for glucose and ketones (a by-product of fatty
acids). High levels of glucose and ketones (in the blood and urine) can
indicate Type 1 diabetes.
Diabetic ketoacidosis occurs when a severe lack of insulin results
not only in a high blood sugar level, but on accumulation in the blood
of products of fat metabolism, ketones, which are acids. This situation
may result in dehydration, hyperventilation (over-breathing) and can
progress to a coma or even death if not urgently treated with insulin
and rehydrating fluids.
It is important not to delay the diagnosis of type 1 diabetes, as it
can be life threatening if left untreated.
You cannot prevent Type 1 diabetes.
However, if you have Type 1 diabetes, you can help prevent or delay
the development of complications by keeping your blood sugar near
normal levels. You should also attend regular medical examinations to
detect early signs of complications. If complications are treated
early, the damage may be stopped, slowed, or possibly reversed.
People who have other health problems in addition to diabetes, such
as high blood pressure or high cholesterol, should also treat those
conditions because these problems can increase the risk for
complications from diabetes. Smoking can increase the risk of
complications.
Type 1 diabetes is associated with many complications including
kidney disease, eye disease, cardiovascular disease and nerve damage,
as well as a reduced quality of life and a shortened life expectancy.
Even with insulin treatment, a lifetime of diabetes can result in
serious long-term consequences. The major organs affected by this
disease include your heart, eyes, kidneys and nerves.
With modern management, and attention to risk factors, many people
with Type 1 diabetes live long, healthy and productive lives.
There are several long-term effects of
diabetes:
• Heart Disease
Diabetes is a well-established risk factor for heart disease.
If you have diabetes you are more than twice as likely to have a
heart attack as non-diabetics (reference 3). Almost 10% of diabetic
Australians (25 years and over) have coronary heart disease compared
with 6% of Australians without diabetes (reference 4).
Blood pressure and cholesterol levels should be monitored as well as
blood sugar.
• Nerve Damage
Nerve damage, or neuropathy, begins as tingling, burning and
numbness in the toes and feet. If the nerves continue to be damaged,
this problem will gradually spread upward.
In uncontrolled diabetes, nerve damage may eventually lead to loss
of feeling in the affected limb. Nerve damage to the feet or poor blood
flow is a dangerous long-term effect of Type 1 diabetes.
• Eye Damage
People with diabetes are at an increased risk of developing diabetic
retinopathy (retinal disease), cataracts and glaucoma. This can lead to
a loss of vision or blindness.
Diabetic retinopathy is the leading cause of blindness in adults
(aged 20–74) years with more than 12,000 new cases of blindness each
year (reference 4).
If identified early, diabetic retinopathy can be treated by laser
surgery. Although it cannot be cured completely, early detection and
treatment can prevent nearly all cases of severe vision loss and
blindness. Despite this, the disease is estimated to account for 17% of
all blindness and vision impairment in Australia (reference 5).
• Kidney Disease
Diabetes is the leading cause of kidney failure (reference 3). Nerve
damage to kidneys can lead to kidney disease or kidney damage, known as
‘diabetic nephropathy’.
Severe damage can lead to kidney failure, which may require
treatment with dialysis or a transplant.
• Other complications
• digestive diseases (coeliac disease, pancreatic cancer,
constipation, diarrhoea, liver disease and gallstones)
• infections
• oral diseases
• mental problems (depression and anxiety)
• problems in pregnancy.
Insulin is a hormone that is made in the pancreas. Within the
pancreas, there are specific areas called the islets of Langerhans.
Beta cells are the predominant cell type within the islets of
Langerhans. Beta cells produce and release insulin.
Patients with Type 1 diabetes produce little or no insulin because
the patient’s immune system has destroyed their beta cells. This is in
contrast to Type 2 diabetes, where beta cells lose function gradually
over time.
The surface of our cells has small channels that allow entry of
glucose into the cell. These channels are not permanently open in
muscle and fat cells and require a trigger to open them. Insulin is
this trigger. In healthy cells, when insulin binds to the insulin
receptor, the glucose channels open and glucose moves from the
bloodstream into the cell. When glucose enters the cell, the glucose is
converted into useable energy for the cell.
Insulin also regulates the normal production of glucose (and
ketones) by the liver. If there is a lack of insulin, there will be
overproduction of glucose. If insulin deficiency is severe there will
also be excessive production of ketones.
If there is no insulin to channel the glucose into cells, the
glucose remains in the blood. High blood glucose levels will result in
long-term health complications.
See our media releases below for all the latest Type 1
diabetes research from the Garvan.
Garvan’s Type 1 diabetes research focuses on two key
areas:
• understanding how and why the immune system turns on itself
and destroys pancreatic beta cells
• identifying potential points in the disease pathway to intervene
and prevent the development of Type 1 diabetes.
Our recent highlights include:
• Discovery of a promising therapeutic target for prevention of
Type 1 diabetes, a molecule known as BCMA, which effectively subdues
the immune cells that cause the disease.
• Demonstrated that a tiny genetic irregularity in the gene
encoding for the growth factor IL-21 greatly boosts its expression,
leading to the development of Type 1 diabetes in mice. The absence of
the irregularity, on the other hand, keeps IL-21 at normal levels and
prevents development of the disease.
• The finding that fats disrupt movement of protein out of the
cellular protein-folding compartment in pancreatic insulin-producing
cells, triggering cell death.
• We discovered a significant missing link in our knowledge
about insulin and how it helps cells absorb glucose. We have shown that
insulin activates a 'motor protein', known as myo1c, which drives
glucose transport molecules to the cell surface.
The Diabetes Vaccine Development Centre (DVDC)
The DVDC was established in 2003 through a major joint initiative of
the National Health and Medical Research Council (NHMRC) and the New
York based Juvenile Diabetes Research Foundation (JDRF). In 2008, the
Garvan Institute became the sole member of the DVDC limited
company.
The Centre's mission is to provide a platform to translate Type 1
diabetes research into improved clinical outcomes; prevention and
therapy.
In 2009, DVDC received an additional $5m from JDRF for a further
three years research in Type 1 diabetes. The DVDC is working towards
improving clinical trials infrastructure which would increase clinical
trial sites linking investigators, study nurses, and hospitals in each
state around Australia.
The DVDC Scientific Program includes:
• A Type 1 Diabetes Prevention Study to determine whether the
administration of insulin via your nose will result in a protective
immune response.
• Study of a new drug, Pepidia-1, in patients with residual
beta-cell function (new onset Type 1 diabetes).
• Testing therapies that target B cells in the immune system to
prevent the immune cells attacking the beta cells of the pancreas.
News
The genetic fuse that may ignite Type 1 diabetes
MEDIA RELEASE:
20 Oct 2009
Garvan scientists have discovered that a tiny genetic irregularity, which boosts the expression of a key gene, may lead to the development of Type 1 diabetes. While there is no cure yet, prevention therapies are on the horizon, making the development of reliable screening tools critical. And that's where the current finding has promise.
Potential preventative therapy for Type 1 diabetes
MEDIA RELEASE:
29 Apr 2009
Immunology researchers at Garvan believe they may have found a preventative therapy for Type 1 diabetes, by making the body's killer immune cells tolerate the insulin-producing cells they would normally attack and destroy, prior to disease onset.
Creating indestructible insulin-producing cells
MEDIA RELEASE:
14 Nov 2007
Dr Shane Grey, head of Garvan's Gene Therapy and Autoimmunity Group, has received $350,000 from the Juvenile Diabetes Research Foundation, as part of their Australian Islet Transplantation Program. The grant will help him genetically modify cells enabling them to defy the body's attempts to reject or kill them after transplant.
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