Cerebral Blood Flow in Insulin Dependant Diabetic Patients

Background: Haemorheologic abnormalities have been reported in diabetes mellitus. Many studies have
reported an alteration in blood rheology and its impact on the cerebral blood flow and cerebrovascular reactivity.
Aim of the work: To assess the role of TCD-Acetazolamide test in the measurement of cerebral blood flow velocity
and cerebrovascular reactivity in type-1 D.M, and to evaluate the impact of different rheological parameters.
Subjects and Methods: We studied 39 type-1 diabetic children and adolescents. They were subdivided equally into
3 groups; I A which included 13 diabetic patients with a disease duration less than 5 years; group IB patients with
a disease duration ranging between 5 and 10 years and group IC patients with a disease duration more than 10
years. Thirteen healthy children and adolescents were selected as a control group. All patients and controls were
subjected to TCD-Diamox examination to measure blood flow velocity of middle cerebral arteries and
cerebrovascular reactivity. Also plasma viscosity, RBCs deformability, hematocrit; glycated hemoglobin% and
lipid profile parameters were measured. Results: The mean value of mean flow velocities of middle cerebral
arteries before Diamox injection and 15 minutes after its injection and mean value of cerebral vasoreactivity in
type-1 diabetics with disease duration more than 5 years were significantly low compared to controls. RBCs
deformability showed a significant positive correlation with mean value of mean flow velocities of middle cerebral
arteries 15 minutes after Diamox injection and cerebral vasoreactivity; while fibrinogen level showed a significant
inverse correlation. Conclusion: This study clearly demonstrated significant alterations in basal cerebral blood
flow, cerebrovascular reactivity and haemorheological parameters in type-1 diabetics. The need to monitor these
changes and to try to modify them early in the course of the disease is clearly validated and justified

MO Abdulghani et al.
235
Cerebral Blood Flow in Insulin Dependant
Diabetic Patients
MO Abdulghani1, A Abd El-Naser1, Gharib Fawi2, N Salah El-Deen1, N El-Beblawy3
Departments of Neuropsychiatry, Ain Shams University1, Neurology, South Valley University2,
Pediatrics3, Ain Shams University
ABSTRACT
Background: Haemorheologic abnormalities have been reported in diabetes mellitus. Many studies have
reported an alteration in blood rheology and its impact on the cerebral blood flow and cerebrovascular reactivity.
Aim of the work: To assess the role of TCD-Acetazolamide test in the measurement of cerebral blood flow velocity
and cerebrovascular reactivity in type-1 D.M, and to evaluate the impact of different rheological parameters.
Subjects and Methods: We studied 39 type-1 diabetic children and adolescents. They were subdivided equally into
3 groups; I A which included 13 diabetic patients with a disease duration less than 5 years; group IB patients with
a disease duration ranging between 5 and 10 years and group IC patients with a disease duration more than 10
years. Thirteen healthy children and adolescents were selected as a control group. All patients and controls were
subjected to TCD-Diamox examination to measure blood flow velocity of middle cerebral arteries and
cerebrovascular reactivity. Also plasma viscosity, RBCs deformability, hematocrit; glycated hemoglobin% and
lipid profile parameters were measured. Results: The mean value of mean flow velocities of middle cerebral
arteries before Diamox injection and 15 minutes after its injection and mean value of cerebral vasoreactivity in
type-1 diabetics with disease duration more than 5 years were significantly low compared to controls. RBCs
deformability showed a significant positive correlation with mean value of mean flow velocities of middle cerebral
arteries 15 minutes after Diamox injection and cerebral vasoreactivity; while fibrinogen level showed a significant
inverse correlation. Conclusion: This study clearly demonstrated significant alterations in basal cerebral blood
flow, cerebrovascular reactivity and haemorheological parameters in type-1 diabetics. The need to monitor these
changes and to try to modify them early in the course of the disease is clearly validated and justified. (Egypt J.
Neurol. Psychiat. Neurosurg., 2005, 42(1): 235-245).
INTRODUCTION
Diabetes Mellitus (DM) is one of the leading
risk factors for cerebrovascular diseases and
haemorheologic abnormalities which have been
reported in it may play an important role in the
pathogenesis of vascular complications1.
The influence of altered haemorheology on
the cerebral blood flow has been always
suggested2,3.
Transcranial doppler ultrasound (TCD) is
used to study the cerebral circulation in human
adults and newborns by determining changes in
blood velocity4. Also, TCD is used and applied to
evaluate the cerebral blood flow5 and
cerebrovascular reactivity using Acetazalamide
(Diamox) IV in type- 1 D.M.6.
The aim of this study is to assess the role of
TCD- Acetazolamide test in the measurement of
cerebral blood flow velocity and cerebrovascular
reactivity in type-1 DM, and to evaluate the
impact of different rheological parameters.
SUBJECTS AND METHODS
This study included 52 children and
adolescents. They were classified into two groups:
Egypt J. Neurol. Psychiat. Neurosurg. Vol. 42 (1) - Jan 2005
236
Group I: Thirty nine type-1 diabetic children and
adolescents attending the Diabetes Clinic,
Children's Hospital, Ain Shams University.
Patients in this group are subdivided into:
Group IA: thirteen patients having type-1
diabetes mellitus with duration less than
five years.
Group IB: thirteen patients having type-1
D.M, with duration ranging between 5
and 10 years.
Group IC: thirteen patients having type-1
D.M for more than 10 years duration.
Group II: thirteen completely healthy children
and adolescents.
All patients and controls were subjected to
the following:

acetaxolomide test to study the blood flow
velocity and vasoreactivity of the cerebral
vessels by measuring blood flow velocity of
the middle cerebral arteries (MCAs) before
IV injection of acetaxolamide and 15 minutes
after its injection in a dose calculated as 10
mg/kg for each subject4.
Statistical analysis
Data were registered and analyzed using the
statistical package SPSS. P values <0.05 were
considered statistically significant. Descriptive
statistics (e.g., mean, standard deviation,
frequencies, and percentages) were calculated and
analysis was performed using the student's t-test,
Chi- square (x2) and correlation coefficient (r).
Pearson’s correlation was used when appropriate.
RESULTS
Demographic data (Table 1)
The present study was conducted on 52
children and adolescents. They were classified
into the following groups.
Group I: 39 type I diabetic patients, they were
subdivided into:
Group IA: 13 patients having type I DM
with duration less than 5 years. Their
ages ranged between 9 and 17 years with
a mean age of 14.54±2.5 years. They
were 7 males and 6 females.
Group IB: 13 patients having type I DM
with duration ranging between 5 and 10
years. Their ages ranged between 11 and
18 years with a mean age of 14.53±2.25.
They were 7 males and 6 females.
Group IC: B patients having type I DM for
more than 10 years duration. Their ages
ranged between 15.5 and 19 years with a
mean age of 17.88±1.19 years. They
were 7 males and 6 females.
Group II: 13 completely healthy children and
adolescents. Their ages ranged between 6.5
and 19 years with a mean age of 10.92±3.88.
They were 7 males and 6 females.
Table (2) shows the laboratory data in group
IA in comparison to control. Glycated Hb%, TC,
HDL-C, LDL-C and T6 were significantly
abnormal (P<0.001, P<0.01, P<0.001, P<0.001
and P<0.05 respectively). Hematocrit %, plasma
viscosity, RBCs deformability and fibrinogen
were not significantly different.
The mean value of MFVs of MCAs before
Diamox injection (at rest) and 15 minutes after its
injection showed no significant difference in
patients in group IA compared to the control
group (Table 3). Also, the mean value of
vasoreactivity (%) showed no significant
difference in to the two groups (Table 3).
MO Abdulghani et al.
237
Table (4) shows the laboratory data in group
IB in comparison to control. All laboratory data
were significantly abnormal, except hematocrit%
and total cholesterol. The mean value of MFVs of
MCAs before Diamox injection and 15 minutes
after its injection was significantly low in patients
(group IB) compared to the control (P<0.001).
Also, the mean value of vasoreactivities % was
significantly low (P<0.001) (Table 5). Similar
results were also observed in the third group of
patients in whom the duration of illness was more
than 10 years, except total cholesterol (TC) was
significantly high in this group (Tables 6 and 7).
When the results of different patient groups
were compared to each other (Tables 8, 9, 10, 11,
12 and 13), it was found that TC and LDL- C
were significantly high in group IC compared to
their mean values in group IB and IA. The mean
value of plasma viscosity and serum fibrinogen
were significantly high in group IB and IC
compared to their mean values in group IA. The
mean value of RBCs deformability was
significantly low in group IB and IC compared to
its mean value in group IA. The mean value of
MFVs of MCA 15 minutes after Diamox injection
and mean value of vasoreactivity were
significantly low in group IB and IC compared to
their mean values in group IA.
Correlation studies, tables (14, 15 and 16)
showed that the duration of diabetes mellitus had
a significant positive correlation with HCT%, TC,
LDL-C, plasma viscosity, fibrinogen level and a
significant inverse correlation with RBCs
deformability, MFVs of MCAs before Diamox
injection, MFVs of MCAs 15 minutes after
Diamox injection and vasoreactivity.
Plasma viscosity showed a significant inverse
correlation with RBCs deformability, MFVs of
MCAs at rest, MFVs of MSAs 15 minutes after
Diamox injection and vasoreactivity, but it
showed a significant positive correlation with
fibrinogen. RBCs deformability showed a
significant positive correlation with MFVs of
MCAs at rest and 15 minutes after Diamox
injection, but fibrinogen showed a significant
inverse correlation.
Table 1. Demographic data.

Table 2. Laboratory data in group IA.

Egypt J. Neurol. Psychiat. Neurosurg. Vol. 42 (1) - Jan 2005
238
Table 3. Cerebral Blood Flow in group IA.

Table 4. Laboratory data in group IB.

Table 5. Cerebral Blood Flow in group IB.

N= number x= mean SD= standard deviation
MFVs= Mean flow velocities ***= Highly significant MCAS = middle cerebral arteries
MO Abdulghani et al.
239
Table 6. Laboratory data in group IC.

Table 7. Cerebral Blood Flow in group IC.

N= number x= mean SD= standard deviation
MFVs= Mean flow velocities ***= Highly significant MCAS = middle cerebral arteries
Table 8. Rheological data in Group IA Group IB.

N= number x= mean SD= standard deviation ***= Highly significant
Egypt J. Neurol. Psychiat. Neurosurg. Vol. 42 (1) - Jan 2005
240
Table 9. Cerebral Blood flow in Group IA Group IB.

MFVs= Mean flow velocities
*= significant
Table 10. Rheological data in Group IA Group IC.

N= number x= mean SD= standard deviation ***= Highly significant
Table 11. Cerebral Blood flow in Group IA Group IC.

Table 12. Rheological data in Group IB Group IC.

N= number x= mean SD= standard deviation
***= Highly significant *= significant
MO Abdulghani et al.
241
Table 13. Cerebral Blood flow in Group IB Group IC.

Table 14. Correlation between different clinical, laboratory, cerebral blood flow velocities and vasoreactivity
values in all patient’s group.

Table 15. Correlation between laboratory and cerebral blood flow velocities and vasoreactivity values in all
patient's group.

Critical value for "r" = +/- 0.2675 * = significant correlation.
TC = Total cholesterol LDL-C =low- density lipoprotein- cholesterol
HDL-C = High density lipoprotein cholesterol RBCs Deform = Red blood cells deformability.
TG = Triglycerides. AD = After Diamox
MCAs = Middle cerebral arteries BD = Before Diamox
MFVs = Mean flow velocities
Egypt J. Neurol. Psychiat. Neurosurg. Vol. 42 (1) - Jan 2005
242
Table 16. Correlation between different rheological and cerebral blood flow velocities and vasreactivity
values in all patient's group.

DISCUSSION
In this study, the cerebral vasoreactivity was
significantly low in those with a disease duration
more than 5 years (group IB and IC) compared to
both controls and those with a disease duration
less than 5 years (group IA). It showed a
significant inverse correlation with diabetes
duration, plasma viscosity and fibrinogen level,
and a significant positive correlation with RBCs
deformability.
This is in agreement with Dandona et al.7 as
they reported a significant reduction in basal
cerebral blood flow (at rest) as age increases and a
significant reduction of cerebral vasoreactivity
with long term disease. Also Rodriguez et al.8
found that a significant inverse correlation
between basal cerebral blood flow (at rest) and
diabetes duration and found no significant
correlation between cerbrovascular reactivity and
glycemic contral which is the same in our study,
however they failed to detect a linear correclation
between cerebral vasoreactivity and diabetes
duration which could be due to the relatively
small sample of their patients.
Others6 found impaired cerebrovoscular
reactivity in patients with disease duration more
than 10 years compared to both controls and
group of short duration and this impaired
cerebrovascular reactivity inversely correlated
with diabetes duration. Meanwhile, they detected
no significant change in basal cerebral blood flow
in the two groups of patients compared to controls
or to each others. This disagrees with our study as
we found an earlier decrease in basal cerebral
blood flow and cerebrovascular reactivity in type -
1 diabetics with a disease duration more than 5
years compared to controls. This may be due to
difference in patients selection in the two studied
populations.
This impairment of cerebral vasoreactivity
and cerebral blood flow could be due to
pathological changes of the small vessels in the
form of microatheroma formation, lipid and
hyaline deposits and thickening of the basement
membrane6 which is not directly related to
glycemic control as evidenced by the absence of a
significant correlation between basal cerebral
blood flow and vosoreactivity and HbAIc % but
could be related to disease duration which
supported by the positive correlation between

administration of acetazolamide. Impaired
cerebrovascular reactivity probably refers to
micro-angiopathic changes of the cerebral vessels
and these changes are part of the generalized
micro angiopathy caused by diabetes6. Also the
disturbed haemorheological parameters (plasma
viscosity, fibrinogen and RBCs deformability)
could be important contributing factors that may
MO Abdulghani et al.
243
accelerate the cerebral microangiopathic and
macroangiopathic changes in type-1
diabetics9,10,11.
In this study, basal cerebral blood flow and
cerebrovoscular reactivity showed a significant
inverse correlation with plasma viscosity and
fibrinogen and significant positive correlation
with RBCs deformability. These rheological
properties of blood are important in determining
blood flow in large and small vessels as in the
microcirculation9.
Fibrinogen level in our study was
significantly high in patients with a disease
duration more than 5 years (group IB and IC) with
a significant positive correlation with disease
duration, plasma viscosity and a significant
inverse correlation with basal cerebral blood flow
and vosoreactivity. This is in agreement with
Zimmermann et al.9 who reported a significant
increase in plasma fibrianogen level in type-1
diabetic patients with disease duration more than
15 years, and Fulsedi et al.6 who documented a
significant increase in fibrinogen level in type-1
diobetic patients with disease duration more than
10 years. Previous researchers12,13 reported also
significant correlation between CBF, fibrinogen
and plasma viscosity.
Regarding RBCs deformability in our study,
it was significantly low in patients with disease
duration more than 5 years, with a significant
inverse correlation with fibrinogen, plasma
viscosity and disease duration and a significant
positive correlation with MFVs of MCAs 15
minutes after diamox injection and cerebral
vasoreactivity. This is consistent with the results
of Linderkamp et al.14.
Concerning plasma viscosity in this study, it
was significantly high in patients with disease
duration more than 5 years, with a significant
positive correlation with disease duration and a
significant inverse correlation with basal cerebral
blood flow velocity and cerebral vasoreactivity.
These results are in agreement with previous
reports9,12,13,15.
These rheological disturbances (increased
fibrinogen and plasma viscosity and decrease
RBCs deformability) in our study could explain
the early decrease in basal cerebral blood flow
and impaired cerebrovoscular reactivity in those
with a disease duration  5 years.
As regard, lipid profile TC, LDL-C and TG
were significantly high and HDL- C was low in all
subgroup of patients compared to controls. This is
in agreement with Fahiem16 and Stern17, however
few other reports18,19 were unable to confirm these
results probably due to different selection criteria.
In conclusion, this study demonstrated
significant alterations in basal cerebral blood
flow, cerbrovascular reactivity and
haemorheological parameters in type-1 diabetics.
All these changes could contribute to the high
incidence of early vascular complications in
diabetic children and adolescents. The need to
monitor theses changes and to try to modify them
early in the course of the disease is clearly
validated and justified.
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الملخص العربي
الإرواء الدموى للمخ فى مرضى السكر المعتمد على الأنسولين
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