Study Genetic Basis of Infantile Onset Diabetes Mellitus Clinical Trial
Official title:
Human Leucocytic Antigen Typing and Mutation of Adenosine Triphosphate Sensitive Potassium Channel Gene in Diabetic Patients Diagnosed Under the Age of One Year.
Diabetes mellitus is a group of metabolic diseases characterized by chronic hyperglycemia
resulting from defects in insulin secretion, insulin action, or both.
According to American Diabetes Association diabetes can be classified into the following
general categories: Type one diabetes (due to beta cell destruction, usually leading to
absolute insulin deficiency), Type two diabetes (due to a progressive insulin secretory
defect on the background of insulin resistance), Gestational diabetes mellitus and specific
types of diabetes due to other causes, example monogenic diabetes syndromes (such as
neonatal diabetes and maturity-onset diabetes of the young, diseases of the exocrine
pancreas, and drug induced diabetes.
Type one diabetes mellitus is one of the most common endocrine and metabolic conditions in
childhood, it accounts for 5-10 percent of all diabetes cases.
Three-quarters of all cases of type one diabetes are diagnosed in individuals under eighteen
years of age.
Data on incidence of childhood onset type one diabetes mellitus are very limited. Data from
large epidemiological studies worldwide indicate that on an annual basis, the overall
increase in the incidence of type one diabetes mellitus is around three percent.
The incidence rate increases from birth and peaks between the ages of ten to fourteen years.
There is increase in incidence of type one diabetes mellitus throughout the world is
especially, marked in young children, Registries in Europe suggest that incidence of type
one diabetes mellitus were highest in the youngest age-group less than four years There is a
seasonal pattern in the onset of type one diabetes mellitus with increased cases during late
autumn, winter, and early spring.
Although most common autoimmune diseases usually affect females, but girls and boys are
equally affected with type one diabetes mellitus in young populations.
The underlying pathophysiological mechanism of the disease is cellular-mediated autoimmune
destruction of the pancreatic beta cells, the rate of beta cell destruction is quite
variable, being rapid in some individuals (mainly infants and children) and slow in others
(mainly adult).
The triggers for the autoimmune attack are not fully understood, but it is now widely
accepted that both environmental and genetic factors contribute to it.
The genetic basic of the disease can be explained as the disease involves many genes, the
risk of a child developing type one diabetes is about five percent if the father has it,
about eight percent if a sibling has it, about three percent if the mother has type one
diabetes.
If one identical twin is affected there is about a fifty percent chance the other will also
be affected.
Some studies of heritability has estimated it at eighty to eighty sex percent. Depending on
locus or combination of loci, they can be dominant, recessive, or somewhere in between. The
strongest gene is located in the major histocompatability class two region on chromosome
sex, at staining region 6p21. It has been reported that only ten percent of those who are
genetically predisposed to type one diabetes mellitus actually develop the disease; however,
that percentage appears to be changing and environmental factors may play an increasingly
important role in determining risk.
Finally, migration studies show an increased type one diabetes mellitus incidence in
population groups who move from an area of low incidence to one of high incidence.
The Possible maternal risk factors for type one diabetes mellitus include maternal age older
than twenty five years, cesarean section, high level of education, infants of mothers with
body mass index of thirty or higher. or higher, infants of white mothers, and maternal
diabetes.
Some studies have reported associations between birth weight and risk of type one diabetes
mellitus, being born large for gestational age, and rapid postnatal growth associated with
an increased risk for type one diabetes.
Other risk factors include: lack of breast feeding, early introduction of cow milk, and
early introduction of gluten containing food before age of four month or late introduction
after the age of seven months, lack of vitamin D supplementation during first year of life
consumption of sugary foods, exposure to certain viruses as cytomegalovirus, measles, or
mumps, childhood vaccination, and maternal-childhood blood group incompatibility.
Neonatal diabetes is a rare cause of hyperglycemia, with an estimated incidence of 1 in
500,000 births.
Two main subgroups are recognized in about equal proportions: permanent neonatal diabetes
and transient neonatal diabetes.The latter remits in infancy or early childhood but may
recur later in life.
Patients with permanent neonatal diabetes typically have reduced birth weight, a reflection
of reduced insulin production in utero, and whilst most are diagnosed with diabetes before
sex months a few rare cases have been reported with diabetes diagnosed between sex and
twelve months of life. In contrast to Type one diabetes permanent diabetes mellitus is not
associated with high risk human leucocytic antigen haplotypes or the presence of pancreatic
autoantibodies, and is most commonly due to activating mutations in either of the genes
encoding the two subunits of the adenosine triphosphate sensitive potassium channel
(potassium channel, inwardly rectifying subfamily J member 11) these mutations also occur in
transient neonatal diabetes. In most of these patients, switching from insulin to oral
sulfonylurea therapy leads to improved metabolic control.
The diabetes presenting within the first sex months of life is unlikely to represent type
one diabetes and usually due to gene mutation, so molecular genetic analysis of this group
of patients should be done. Additionally, individuals with a diagnosis of diabetes after sex
months-of-age should also receive genetic analysis if their diabetes presentation is
atypical for type one diabetes, has features consistent with a known monogenic cause, or if
there are additional affected family members with a history of neonatal diabetes.
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