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العنوان
Kallistatin as a Marker of Microvascular
Complications in Children and Adolescents
with Type 1 Diabetes Mellitus\
المؤلف
Salem, Shaimaa Mohamed Ahmed.
هيئة الاعداد
باحث / Shaimaa Mohamed Ahmed Salem
مشرف / Mohamed Abo El-Asrar
مشرف / Nevine Gamal Andrawes
مناقش / Eman Abdel Rahman Ismail
تاريخ النشر
2014.
عدد الصفحات
192P. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
طب الأطفال ، الفترة المحيطة بالولادة وصحة الطفل
تاريخ الإجازة
1/1/2014
مكان الإجازة
جامعة عين شمس - كلية الطب - الاطفال
الفهرس
Only 14 pages are availabe for public view

from 192

from 192

Abstract

SUMMARY
iabetes Mellitus (DM) is a group of metabolic diseases
characterized by hyperglycemia, resulting from defects
in insulin secretion, insulin action or both. Type 1 diabetes
mellitus is caused by deficiency of insulin secretion due to
pancreatic β-cell damage.
The chronic hyperglycemia of diabetes is associated with
long-term damage, dysfunction, and failure of different organs
resulting in microvascular disease, such as nephropathy,
retinopathy or neuropathy, and also macrovascular disease as
atherosclerosis.
In diabetes, microvascular disease may be mediated by
disturbances in the levels of or balance of pro- and antiangiogenic
factors, such as (anti-angiogenic) kallistatin.
Kallistatin (KS) is a serine proteinase inhibitor (serpin),
was first identified as a tissue kallikrein-binding protein. It has
anti-angiogenic, anti-oxidant and anti-inflammatory effects,
anti-tumor, vasodilator effects. KS is synthesized primarily in
the liver, but it is also widely expressed in organs such as the
kidney, heart, and blood vessels. It has been found elevated in
serum samples of patients with diabetes. However, circulating
kallistatin levels in type 1 diabetic children and adolescents
have not been widely explored.
Our study aimed to determine the level of serum
Kallistatin in children and adolescents with type 1 diabetes as
an early marker for micro-vascular complications as
nephropathy, retinopathy or neuropathy and assess its relation
to clinicolaboratory characteristics of the patients. Plasma
Kallistatin levels were determined by immunosorbent assay
(ELISA).
This cross sectional study was carried out on 65 children
and adolescents with type 1 DM, with disease duration 5 years
or more, attending the Pediatric Diabetes Clinic, Ain Shams
University, from from April 2012 to April 2013. Their mean
age was 14.1 ± 2.6 years (range, 9-18years), with mean disease
duration 6.9 ± 1.7 years. Another group of 35 age- and sexmatched
healthy individuals was enrolled as controls with a
mean age was 13.2 ± 3.4 years (range, 4-18 years).
All included patients were subjected to detailed medical
history (age of onset of diabetes, diabetes duration, insulin
therapy, acute metabolic complications, symptomatic
hypoglycemic attacks or episodes of diabetic ketoacidosis and
chronic microvascular complications: retinopathy and
neuropathy, thorough clinical examination stress on asessment
of anthropometric measures and routine work up including;
FBG, fasting lipid profile, mean HbA1c%, and CRP. Also,
serum levels of Kallistatin were measured (ELISA).
The studied diabetic patients were subdivided into 2
groups: patients with microvascular complication 49.2% (32
patients) and patients without 50.8% (33 patients).
Among patients with complication the percentage of
each complication was as follows: diabetic nephropathy
(32.3%), retinopathy (10.7%), peripheral neuropathy (12.3%).
The mean serum kallistatin levels were significantly
increased in patients with micro-vascular complications (9.53 ±
1.9 ng/ml) and non-complicated patients (4.3 ± 1.54 ng/ml)
compared to healthy controls (1.39 ± 0.55 ng/ml) (p<0.01).
Furthermore, comparison of mean serum kallistatin
levels between type 1 diabetic patients with different stages of
albuminuria revealed that patients with microalbuminuria (9.05
± 2.15 ng/ml) had increased levels than normoalbuminuric
patients (6.48 ± 3.15 ng/ml ) (p<0.01).
Also mean serum kallistatin levels was correlated to each
single diabetic complication as follows, in nephropathy (9.5 ±
1.6), retinopathy (7.58 ± 1.59 ng/ml), peripheral neuropathy
(10.7 ± 1.86 ng/ml).
Patients with microvascular complications showed to
have longer diabetes duration, higher systolic and diastolic
blood pressure, mean fasting blood sugar, HbA1C, CRP,
triglycerides, total cholesterol, LDL and serum kallistatin. And
lower HDL than patients without complications.
A significant positive correlation was found between
mean serum kallistatin levels diabetes duration, systolic BP,
diastolic BP, FBS, HbA1c, triglycerides, total cholesterol and
LDL and a significant negative correlation with HDL it type 1
diabetic patients.
Multiregression linear analysis showed that FBS, HbA1c,
cholesterol and LDL were independently related to mean serum
kallistatin levels in type 1 diabetics.
ROC curve analysis revealed that the cutoff value of
serum kallistatin at >6.0 ng/mL could differentiate complicated
from non-complicated cases with a sensitivity of 96.87%,
specificity of 93.75% and area under the curve was 0.979.