الفهرس 
Diabetes Mellitus Prevalence and StatisticsOnly 14 pages are availabe for public view
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Abstract
Diabetes mellitus especially T2DM is a complex metabolic
disorder having a great worldwide concern, being associated with huge
economic burden, and decreased quality of life. The β-cell dysfunction
is a critical component in the disease pathogenesis superseding the long
studied IR. Islet β-cells inflammation is regarded as one of the early
events in β-cell dysfunction, thus the role of β-cells produced- and
secreted- proinflammatory cytokines became of interest in the research
field in the last decades.
In this context, some cytokines were suggested to be implicated
in β-cell dysfunction. Among these, the novel PANDER and the wellknown MCP-1 were shown to negatively influence the β-cell function
through data derived from studies on humans and rodents islets.
However, their role in β-cell dysfunction clinically in well-established
T2DM patients with different disease durations and how they can be
used to clinically reflect the β-cell status have not been investigated yet.
Thus, the current study was designed as an attempt to investigate the
level of each of them in T2DM patients with different degrees of β-cell
dysfunction as well as to investigate the association of each of them
with various anthropometric and biochemical parameters as well as the
interrelationship among both of them.
In order to fulfil our aim, this study was conducted on 79
subjects divided into the following four groups:
A) Control group (group I): consisted of 16 healthy control
volunteers (13 males and 3 post-menopausal females).
B) Recently diagnosed T2DM patients on OHA (group II):
consisted of 24 patients (17 males and 7 post-menopausal females).
C) Long-standing T2DM patients on OHA (group III):
consisted of 21 patients (14 males and 7 post-menopausal females). D) Long-standing T2DM patients on insulin &/or OHA (Group
IV): consisted of 18 patients (9 males and 9 post-menopausal females).
Anthropometric parameters (BMI and WC), biochemical
parameters (FBG, HbA1c, lipids profile, serum intact PI, C-pepide,
insulin, HOMA2-IR, HOMA2-%β, PI/C-pep and PI/I ratio) and
cytokines of interest (serum PANDER and MCP-1) were determined in
different study groups. Then the correlations between these parameters
were examined statistically to gain more insight into our results.
The results of the current study can be summarized as follows:
1) Significantly elevated levels of FBG, HbA1c, TG, TC, LDL-C, were
observed in T2DM groups as compared to the control group.
2) The β-cell assessment markers; PI, PI/C-pep and PI/I ratios were
significantly increased, whereas HOMA2-%β was significant
decreased, in T2DM groups compared to the controls, indicating a
deterioration of β-cell function among our study groups, thus it s
reasonable to speculate that T2DM is a duration-dependant disease.
3) Serum PANDER levels were significantly elevated in longstanding T2DM groups compared to the recently diagnosed T2DM
patients and the controls, therefore, it is reasonable to speculate that
high PANDER serum levels greatly reflect the worsening stages of
the disease.
4) The levels of serum MCP-1 were significantly elevated in all
diabetic groups compared to control, which not only confirm its
role in T2DM clinically but also highlight that this role can be
associated with both the early and late stages of the disease
pathogenesis.
5) Interestingly, PANDER levels were significantly positively
correlated to FBG, HbA1c, PI, PI/C-pep and PI/I ratio, as well as
negatively correlated to HOMA2-%β. However, those levels failed
to show any significant association to HOMA2-IR. Thus, it is
reasonable to speculate that this novel cytokine is closely related to T2DM pathogenesis specifically through affecting the β-cell
dysfunction; the critical component of the disease.
6) The levels of MCP-1 were found to be significantly correlated
positively to FBG, HbA1c, PI, PI/C-pep, PI/I and HOMA2-IR and
negatively to HOMA2-%β. Thus, we can speculate that this
cytokine is related to T2DM not only through its widely confirmed
role in IR, but also through negatively influencing β-cell
functionality that was confirmed clinically in this study.
7) Finally, we could not clinically confirm the suggested association
between both cytokines, concluded from a previous study on
pancreatic islets, as the clinical association between PANDER and
MCP-1 in our study groups failed to reach statistical significance.
In conclusion, our results showed that diabetic patients at
different stages of diabetes are exhibiting different degrees of β-cell
dysfunction. In addition, we demonstrated that PANDER and MCP-1
can be clinically regarded as two interesting β-cell dysfunction
associated-cytokines that may have potential abilities to predict β-cell
status in diabetic patients. Assessment of these markers not only shed
light on potential new mechanisms involved in β-cell dysfunction, but
also might propose promising new therapeutic targets in the future to
preserve β-cell function in diabetic patients.