الفهرس 
Type 1 Diabetes Mellitus And ItsOnly 14 pages are availabe for public view
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Abstract
T1DM or more accurately type 1A diabetes is thought to arise
from selective immunologically mediated destruction of the insulinproducing
β-cell in the pancreatic islets of Langerhans with consequent
insulin deficiency, this occurs in individuals in whom genetic
susceptibility outweighs genetic protection and is probably initiated by
environmental factors not yet clearly defined, the disease arises via a
cellular-mediated immune process most probably by a specific reaction to
one or more β-cell proteins (Autoantigens).
The incidence of T1DM
The incidence of T1DM in children has been increasing by 3% to
5% per year worldwide since the 1960s, the environmental factors
responsible for this epidemic remain unknown, the number of people
living with diabetes is now put at 382 million up from 366 million at
2011 expected to rise to 592 million by 2035.
The geographical incidence of type 1 diabetes mellitus (T1DM)
varies widely worldwide, both genetic and environmental factors have
been implicated. There are no reported studies on the epidemiology of
childhood T1DM in Egypt. the incidence, prevalence and demographic
characteristics of T1DM in children (0-18 years) in the Nile Delta
region, Egypt. between(1994-2011). (55.7%) were females and (58.4%)
were from rural areas. Patients presented most frequently in the(5-10y)
and in winter months, concluding that, T1DM incidence and prevalence
were found to show an increase over the past 18 years (1994-2011). and
were higher in females and more cases from rural areas.
SUMMARY
2015
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Complications of T1DM:
Hypoglycemia is the most common complication of T1DM in
childhood. It can occur in any child in whom the dose of administered
insulin exceeds insulin requirement. Severe and recurrent hypoglycemia
can lead to acute and permanent neurologic complications.
Microvascular complications T1DM:
Diabetic nephropathy occurs in 20–40% of patients with
diabetes and is the single leading cause of end stage renal
disease, persistent albuminuria in the range of 30–299 mg/
24 h has been shown to be an early stage of diabetic
nephropathy in T1DM.
Diabetic Retinopathy(DR), micro aneurysms count predicts
long-term incidence of proliferative DR and diabetic macular
edema (DME). This demonstrates that early DR is a warning
sign of late retinopathy complications.
Diabetic Neuropathy(DN) is the most common complication
of diabetes mellitus affecting as many as 50% of patients
with T1DM, DN involves the presence of symptoms or
signs of peripheral nerve dysfunction in people with diabetes
after other possible causes have been excluded.
Macro Vascular Complications:
The macrovascular complication are responsible for approximately
80 % of mortality of diabetes patients, although patients with diabetes
commonly experience and complain of microvascular complication ,the
greatest cause of death in people with diabetes is cardiovascular disease.
Prediction of T1DM:
Diabetes progresses from genetic risk to immune activation to β-cell
injury to impaired insulin secretion to glucose intolerance and finally to
frank disease. Although practitioners are most familiar in the clinical
setting with the latter stages of the disease pathogenesis, identifying
individuals at risk for T1DM before substantial islet injury is our best
chance for diabetes prevention
There is a need for diagnostic biomarkers to detect more accurately
individuals with pre-diabetes to accelerate targeting for prevention and
intervention strategies. The researches generated five major categories of
markers that are either currently used or forthcoming: genetic,
autoantibody, risk score quantification, cellular immunity and β-cell
function. The current standard used focuses on autoimmune pathology
and disease-associated auto antibodies.
Prevention of T1DM
Prevention of T1DM would require interventions aimed to (1)
Avoiding exposure to environmental triggers early in life(primary
prevention); as TRIGR study, the primary and final endpoint of TRIGR,
meaning clinical diabetes by the age of 10 years, will be reached early in
2017. If the intervention works and significantly reduces the cumulative
incidence of T1DM by the age of 10 years, this would imply that infants
at increased risk of T1DM should be weaned to a highly hydrolyzed
formula. If the intervention has no effect, the study recommendation
would state that weaning to a highly hydrolyzed formula does not
decrease the risk of T1DM. Another study was BABYDIET study which
aiming to determine whether delaying the introduction of gluten in infants
with a genetic risk of islet autoimmunity may reduce the risk of T1DM associate islet autoimmunity, this study had no effect on appearance of
islet antibodies with about 12% of children in both groups developing
antibodies over three years.
(2) Interfering with the autoimmune cascade that occurs during β-
cell destruction (secondary prevention or intervention). Two studies were
reported using acute immunosuppressive treatments with humanized
antibodies against a T-cell antigen(CD3) for recently diagnosed T1DM
patients, the first study showed that patients who were treated with the
antibody had better β-cell function and lower exogenous insulin
requirements after 1 year than patients in the placebo group, a subsequent
study on a larger sample of patients showed that the effects on β-cell
function and insulin requirements could be maintained for up to 18
months however very few patients became insulin-free in these trials .
(3) Halting or reversing β-cell loss after clinical presentation of
T1DM(tertiary intervention) with the aim of easing day-to-day
management of diabetes and diminishing complications. Early trials that
used broad-spectrum immunosuppressive drugs (Cyclosporine,
Azathioprine, Anti-Thymocytic Globulin) have shown some benefits in
patients with recent onset of T1DM but the short- and long-term side
effects limited their use.
Once T1DM has developed, immune interventions are unlikely to be
effective because the vast majority of β-cell have been destroyed, at this
stage effective interventions would include β-cell implantation, gene
therapy or of stem-cell–derived β-cell. Islet cell transplantation enjoyed a
period of success. Genetic engineering and stem cell biology hold out the
most hope in the long run for a cure for T1DM and elimination of the
need to inject insulin.