الفهرس 
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Abstract
Over the last 50 years type 2 diabetes mellitus (T2DM) is growing rapidly. Today
diabetes is present in over 235 million individualsworldwide. Over the next few decades a
remarkable increase in diabetes is projected. Estimate of the global prevalence of diabetes
in the year 2010 and the projections for 2030 surprisingly indicate that, over 439 million
people are projected to suffer from this condition and that Egypt will be ranked as the 10th
country worldwide which has the highest number of people with diabetes, making it one of
the most serious diseases of humankind.
Identifying the etiology and the early detection oftype 2 diabetes are keys to
prevention. So there is a great need for early detection tool or a predictor to determine the
risky factors for individuals to develop T2DM. So, with the administration of proper drugs
and applying the individuals to controlled diet or physical intervention, the development of
disease or its complication can be prevented.
The study of early predictors in human is difficultbecause it require large cross-sectional prospective study. So using animal modelsof T2DM is of great importance to
illustrate various types of etiological and pathogenic mechanisms that could also operate in
humans. Among these models, diabetes induced in rats by neonatal streptozotocin (STZ)
administration (so-called “n-STZ models”). This model has many advantages over other
models of diabetes and is considered to be one of the suitable experimental animal models
of T2DM.
This study focused on the early changes of circulating three adipocytokines during
the course of T2DM induction due to the documented role of adipose tissues in the
pathogenesis of T2DM.
This study interested in investigating the role of three adipocytokines, namely; tumor
necrosis factor-alpha (TNF-α), visfatin and vaspin,as an early markers or predictors during
the experimental induction of T2DM using n-STZ rat model. Rat neonates were injected
intraperitoneally with STZ (100mg/Kg) at the 5
th
day of birth (diabetic group). The control
neonates were injected with saline at the 5
th
day of birth (control group). All rats will be
followed up for 5 months and a blood sample will bewithdrawn from each rat every one
month. The serum will be used for the determinationof the study parameters; fasting blood
sugar, insulin, HOMA-IR, lipid profile, TNF-α, vaspin and visfatin.
The results of this study indicated that by 3
rd
month of age, n-STZ rats show higher
weight and FBS and lower insulin level than controlrats. By age 4 month and thereafter
mild hyperglycemia was developed (130–180 mg/dL) and insulin deficiency was
evidenced together with insulin resistance as indicated by increased HOMA-IR in n-STZ
rats compared to control rats.
The defect in glucose homeostasis in n-STZ rats is associated with derangements in
the lipid metabolism as indicated by age-dependent elevated levels of triglycerides and
total and LDL-cholesterol and decreased level of HDL-cholesterol.
The patterns of changes of the adipocytokines are interesting. TNF-α show age-
dependent increase in control and diabetic rats. The n-STZ diabetic rat shows a significantly higher TNF-alpha level from the second month of age compared to control
rats in males while in females at the third month of age. The correlation studies indicated
that TNF-α is positively correlated with weight, FBS, insulin and HOMA-IR in n-STZ
diabetic rat model males and females.
The results of vaspin show an interesting pattern of changes. First, it shows gender
difference as female rats (normal or diabetic) havehigher level than male rats. Second,
male rats of the diabetic group show a significant higher level of vaspin from the second
month of age and show biphasic change; during earlylive it show a gradual increase with
age from the first month of age until the fourth month after which it begin to decrease
(coincidence with hyperglycemia). Female rats of the diabetic group show abnormal high
level of vaspin only after the 4
th
month of age.
As vaspin, visfatin show gender difference; female rats have higher level than male
rats (normal and diabetic). There is no significantchange observed in n-STZ rats from
control until 4
th
month after which the visfatin level becomes significantly elevated.
However, the individual results of TNF-α, vaspin and visfatin have little value as
independent predictor for T2DM, combinations of their values as ratios may produce more
clear results. While TNF-α/vaspin and TNF-α/visfatin ration didn’t show significant
differences between normal rats and n-STZ diabetic rat in model male or female,
visfatin/vaspin ratio show great decrease in the male diabetic model during early
development of the diseases while after 5
th
month of age and the incidence of
hyperglycemia the ratio show no significant change.
When we use ratio of the visfatin to insulin the pattern obtained show significantly
increased values as early as the first month of agein male and female n-STZ rats that could
be used for predicting the development of T2DM. Also, the ratio of vaspin to insulin could
be used especially in males while in females its value become significant only from the 3
rd
month of age.
from the results of the present study we can conclude that:
1- TNF-α show significant elevation in the n-STZ rat model of T2DM from 2
nd
month of
age in male and from 3
rd
month in female
2- Vaspin show gender difference between male and female. In male n-STZ rat model
show biphasic change; during early live it show a gradual increase with age from the
first month of age until the fourth month after which it begin to decrease (coincidence
with hyperglycemia)
3- Visfatin show gender difference. In n-STZ rat model of T2DM visfatin show no
significant change until 4
th
month of age
4- The individual results of TNF-α, vaspin and visfatin have little value as independent
predictor for T2DM
5- Assessment of the adipocytokines vaspin and visfatin together with insulin and
calculating visfatin/vaspin and visfatin/insulin ratio may provide useful information
about the prediction for the development of T2DM.