بسم الله الرحمن الرحيم. Immunological markers in the pathogenesis of type 1 diabetes in Saudi children. Diabetes Mellitus (DM). Definition : a group of metabolic diseases that result from insulin deficiency, defect in insulin action, or both . DM is characterized by hyperglycemia
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in the pathogenesis
of type 1 diabetes in
Definition: a group of metabolic diseases
that result from insulin deficiency, defect
in insulin action, or both.
polydipsia, weight loss, polyphagia,
Type 1 diabetes mellitus
Type 2 diabetes mellitus
Other specific types:
Genetic defects of beta-cell function Infections
Genetic defects in insulin action Uncommon forms of immune-
Diseases of the exocrine pancreas medicated diabetes
Endocrinopathies Other genetic syndromes
Drug or chemical-induced sometimes associated
Gestational diabetes mellitus
absolute (not relative) insulin deficiency
IDDM incidence in different countries
per 100,000 / year
a) To study the autoimmune pathogenesis
of type 1 diabetes in Saudi children
b) To establish the specialized tests for the
detection of autoantibodies in type 1
c) To study 1st degree relatives of type 1
diabetes patients to establish the
degree of risk due to the presence of
these antibodies in genetically
2.First Degree Relatives (n=60):
Median age 7.5yrs (8/12 – 20 yrs)
Below 20 yrs
No history of endocrine disease
Median age: 7 (1- 17 yrs)
Serum is separated by centrifugation
& stored at –20°C
ELISA kits (Biomerica) to detect the 3 autoantibodies :
antibodies was added
The wells were washed so
what remains are the
Conjugate was added which
will bind with the complex formed
is then read at 405nm
The resulting color
Results were grouped into:
diabetes in Saudi children
Two peaks of disease incidence:
First peak in early childhood (3- 4 yrs).
Second peak at pubertal age (9-12 yrs)
Relation of onset of type 1 diabetes to environmental
Season Number Percentage
Hot(summer) 58 48
Cold(winter) 40 32
Mild(spring, autumn) 27 22
d) The relation of birth order in the family and the risk of developing type 1 diabetes
Number of earlier studies showed that first born child has a higher risk for type 1 diabetes.
Relation of onset of type 1 diabetes and history of recent infection (n=157 )
Similar result was also reported from Japan. While Venezuelan diabetic children gave history of infection prior to diagnosis.
monthly income of their families
Risk of type 1 diabetes is related to social class ( Pop. Density;
Educational Level; Residence and Income)
Average family monthly Percentage
income Number %
< SR5000 64 36
SR5000 – < SR10000 65 36
SR10000 48 27
Japan, USA and UK
Relation Number Percentage
Father 9 4.6
Mother 3 1.5
Siblings 20 10.0
Father & Sibling 3 1.5
Mother & Sibling 0 0.0
At least 1 affected
relative 29 15.0
2) They are more prevalent in healthy relatives of type 1 diabetes than the general population they may provide clues to the etiology of the disease, thus contributing to the preventive or therapeutic modalities.
3) They confirm the autoimmune origins of the disease in patients who are difficult to categorize. So they improve the classification of diabetes.
In newly diagnosed patients:
diagnosed Saudi patient may
be due to:
No statistical significant differences in the frequency of antibodies and different age groups.Similar to Swedish children.
No relation between the frequency of the three
autoantibodies and sex
The frequency of autoantibodies and
history of recent infection:
Vahasalo et al (1996): infection during the preceding year increases the frequency of both ICA and IAA at diagnosis.
family history of type 1 diabetes:
Similar negative finding was reported by Rewers and Norris (2002) for ICA and IAA.
and the duration of the disease
with longer duration of the disease:
Antibodies No. of Cases Percent
ICA 19 28
IAA 36 52
GADA 40 58
ICA and/or GAD 43 62
ICA and/or IAA 40 58
GAD and/or IAA 51 74
ICA and/or IAA and/or GADA 52 75
IAA in relatives:
GADA in relatives:
The relation of frequency of autoantibodies with age in first-degree relatives
developed the disease
5 yrs old male with an affected brother developed the disease, 3 months aftertaking the first blood sample.
He was positive for IAA only.
At time of diagnosis he also developed GADA.
developed the disease
6 yrs old girl who developed the disease 3 weeks aftertaking the blood sample.
Her blood sample was positive for IAA and GADA.
This girl had an affected father, brother, and two sisters. Her mother also has hyperthyroidism.