The HLA region
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. Different versions (or alleles) of these
genes can put a person at risk for — or prevent them from
— developing Type 1 diabetes. One gene in the HLA region
that plays an important role in diabetes is called DR. People
can inherit one form of DR from their mother and one form
of DR from their father. It's the combination of these two
forms of the gene that determine a person's overall risk.
Two forms of DR, designated DR3 and DR4, are present in 95
percent of Type 1 diabetics, and 30 percent have inherited
both DR3 and DR4. This is in contrast with the general
population, where only 50 percent of people have DR3 or
DR4 and 1 to 3 percent have both.
HLA allele Risk level
DR 1 Slight
DR 2 Protective
DR 3 Significant
DR 4 Significant
DR 5 Slight
DR 6 Neutral
DR 7 Protective with risk in Africans
DR 8 Neutral
DR 9 Risk in Chinese and Japanese
• If a person inherits two short VNTR regions, they are two to five
times more likely to develop Type 1 diabetes than a person with
at least one long VNTR.
• The longer (protective) VNTR region seems to decrease the
amount of insulin produced in the pancreas. This finding may
seem contradictory, because the longer VNTR also protects a
person from developing diabetes. However, researchers have
found that insulin is produced in the thymus during development.
(The thymus is also where many cells in the immune system
develop). During this time, the longer VNTR causes more insulin to
be produced. Researchers think that when developing immune
cells are exposed to high levels of insulin, they learn to identify
insulin and are less likely to react against it and cause diabetes
later in life.
• It's a group of metabolic condition that occurs together in one person
increasing the risk of heart disease, stroke & D.M.
Role in diabetes:
the driving force behind the insulin resistance that ultimately leads to •
.hypertension, dyslipidemia, hypercoagulability and inflammation
Even normal-weight individuals with increased visceral fat can become •
insulin resistant. The take-home message was that nutrient excess, obesity,
and visceral adiposity are the primary contributors, and the
pathophysiologic consequences that follow are a direct result of increased
.plasma free fatty acids and insulin resistance
Hyperglycemia is one of the metabolic syndrome criteria •
There is increasing evidence that coronary heart disease associated with •
the metabolic syndrome and type 2 diabetes is in large part as result of
Visceral adiposity is also associated with reduced adiponectin, which is an •
"insulin-sensitizing protein" with vascular protective effects
Prevention of type 1 Diabetes
• Since type 1 diabetes is an idiopathic disease
or may occur due to genetic abnormalities. So
its control is somehow difficult.
• Lots of trials have been done to prevent the
occurrence of diabetes,BUT these trials were
proved to be useless
• But other techniques have been suggested
and its results have not yet been proven.
The first trial done to prevent type 1
diabetes in 2002
• Preventing Type 1 diabetes is an active area of
research. Some of the techniques that
researchers are looking into are:
• Vaccines to prevent the immune system from
destroying the pancreas cells. This technique has
been effective in mice, but has not yet been
tested in humans.
• Giving people with a family history of diabetes
injected or oral insulin before they develop
diabetes. This approach has been effective in
mice,but it proved its failure with human beings
Prevention of type 2 diabetes
Before people develop type 2 diabetes, they almost always
have "pre-diabetes" -- blood glucose levels that are higher
than normal but not yet high enough to be diagnosed as
Take our diabetes risk test to see if you are at risk for
developing diabetes. Diabetes is more common in African
Americans, Latinos, Native Americans, Asian Americans and
is a powerful new risk assessment tool. It can be used to
explore the effects of a wide variety of health care
interventions, including losing weight, stopping smoking, and
taking certain medications.
Diabetes Prevention Program study conclusively showed that
people with pre-diabetes can prevent the development of type
2 diabetes by making changes in their diet and increasing their
level of physical activity.
Keeping an eye on these risk factors -- keeping them "in check"
Keeping an eye on these risk factors -- keeping them "in check"
-- can help you prevent diabetes and heart disease . .
-- can help you prevent diabetes and heart disease
What is the diabetes prevention
• was a major multicenter clinical research
study aimed at discovering whether modest
weight loss through dietary changes and
increased physical activity or treatment with
the oral diabetes drug metformin
(Glucophage) could prevent or delay the
onset of type 2 diabetes in study
• The DPP contributed to a better understanding of how diabetes
develops in people at risk and how they can prevent or delay the
development of diabetes by making behavioral changes leading to
• DPP researchers continue to examine the roles of lifestyle and
metformin and other diabetes medications in preventing type 2
• They also continue to monitor participants to learn more about
the study’s long-term effects through the Diabetes prevention
Program Outcomes Study (DPPOS).
• DPPOS is examining the impact of long-term risk reduction on
diabetes-related health problems, such as nerve damage and
heart, kidney, and eye disease.
• The National Institute of Diabetes and Digestive and kidney
Diseases supports a wide range of research related to the DPP,
such as studies that assess cost-effective methods of delivering
lifestyle modifications in group settings and over the internet, as
well as methods to sustain behavior change and weight loss
• Weight gain is a common side effect for people who
take insulin — a hormone that regulates the
absorption of sugar (glucose). The more insulin you use
to control your blood sugar level, the more glucose
that gets into your cells and the less glucose that's
wasted in your urine. Glucose that your cells don't use
accumulates as fat. If you continue to eat as you did
before, you'll likely gain weight when you start taking
• Think about it this way: Before starting insulin, you
could eat more food than you needed without gaining
weight because your body didn't use the food
properly. But with insulin, your body uses food
properly, and you may need less food than you think.
Pancreas transplants are generally performed
together with or some time after a kidney transplant?
• but why with kidney?
• 1-new kidney requires taking
immunosuppressive drugs such as
ciclosporin. Nevertheless this
allows the introduction of a new,
functioning pancreas to a patient
with diabetes without any
• 2-pancreas transplants alone can
be wise in patients with extremely
labile type 1 diabetes mellitus
insulin-producing cells are
transplanted into body organs
• where is residence of cells ?
• in liver
• 1-less invasive
• 2-higher rates of success
• Recent studies have shown that islet cell transplants have progressed to the point
that 58% of the patients in one study were insulin independent one year after islet
• 1- immunosuppressant drugs must be given to prevent the body from rejecting
the transplanted cells.
• 2-failure of transplant
• but scientists in New Zealand are also looking into placing them within a protective
housing derived of seaweed which enables insulin to flow out and nutrients to
flow in while protecting the islets from immune system attack via white blood cells
• role of TNF alpha :is part of the immune system. It helps
the immune system distinguish self from non-self tissue.
People with type 1 diabetes are deficient in this substance
• Dr. Denise Faustman theorizes that giving
Bacillus Calmette-Guérin (BCG) which stimulates TNF-α
production. TNF-α kills the white blood cells responsible for
destroying beta cells,
• prevents, or reverses diabetes. She has reversed
diabetes in laboratory mice with this technique.
a vaccine has been proposed
• clinical trial :GAD65, an autoantigen involved in
type 1 diabetes, has in clinical trials delayed the
destruction of beta cells for at least 30 months
• 1-Phase III trials are under way in the USA and in
• 2- Two prevention studiehere the vaccine is given
to persons who have not yet developed diabetes,
will start in 2009(3)
Stem cells approach
• a-South Korea
• In January 2006, a team of South Korean scientists has
grown pancreatic beta cells, which can help treat diabetes,
from stem cells taken from the umbilical cord blood of
• b-University of North Carolina
• In September 2008, scientists from the University of North
Carolina at Chapel Hill School of Medicine have announced
their success in transforming cells from human skin into
cells that produce insulin
• BUT HOW ?
• The skin cells were first transformed into stem cells and
then had been differentiated into insulin-secreting cells.
Gene therapy approach
• A-viral vector method :
• 1-oral medication, consisting of viral vectors containing the insulin
sequence, is digested and delivers its genes to the upper intestines
• 2-Those intestinal cells will then behave like any viral infected cell, and will
reproduce the insulin protein
• 3-The virus can be controlled to infect only the cells which respond to the
presence of glucose, such that insulin is produced only in the presence of
high glucose levels.
• 4-BUT Due to the limited numbers of vectors delivered, very few intestinal
cells would actually be impacted and would die off naturally in a few days
• 5-BUT SOLVED -----------amount of oral medication used again and so on
• B-cure the cause of beta cell destruction (5)
• C-turn duodenum cells and duodenum adult stem cells into beta cells (6)
• not well understood but this what happens
• 1-By delivering beta cell DNA to the intestine cells in the duodenum, a few
intestine cells will turn into beta cells
• 2-adult stem cells will develop into beta cells
• 3-This makes the supply of beta cells in the duodenum self replenishing,
and the beta cells will produce insulin in proportional response to
• future developments:
• A-When insulin pump technology is combined with a continuous
blood glucose monitoring system, the technology seems promising
for real-time control of the blood sugar level. Currently there are no
mature algorithms to automatically control the insulin delivery
based on feedback of the blood glucose level.the system may
function as an artificial pancreas
• B-Insulin pumps are being used for infusing pramlintide (brand
name Symlin, or synthetic amylin) with insulin for improved
postprandial glycemic control compared to insulin alone.
• C-bolus calculators: Pump software helps by calculating the dose for
the next insulin bolus. The user enters the grams of carbohydrates
to be consumed, and the bolus "wizard" calculates the units of
• D-custom alarms: The pump can monitor for activities during
specific times of day and alarm the user if an expected activity did
not occur. Examples include a missed lunch bolus, a missed blood