Abnormal diastolic function in patients with type I diabetes and early nephropathy

Abstract

Left ventricular diastolic function was assessed by pulsed Doppler echocardiography in non-diabetic controls (n = 11) and in patients with type 1 diabetes without microvascular disease (n = 16; diabetic controls), with microalbuminuria (n = 9), or with early persistent proteinuria (n = 11). The peak filling velocities during the early and atrial phases of left ventricular diastole and their ratio (E:A ratio) were measured. All patients with diabetes had a normal serum concentration of creatinine and exercise electrocardiogram. The mean E:A ratio was significantly lower in those with proteinuria than in the diabetic controls because of an increase in peak atrial filling velocity; most patients with proteinuria had an abnormal E:A ratio of less than 1.0. Multiple regression analysis showed that systolic blood pressure was the major determinant of both the peak filling velocity during the atrial phase of diastole and also left ventricular mass. Blood pressures were significantly higher in the proteinuria group than in the diabetic controls. Glycaemic control and autonomic function did not influence diastolic filling. The slightly raised blood pressures at the earliest stages of diabetic nephropathy are sufficient to alter left ventricular diastolic compliance--this may reflect early hypertensive heart disease. These data do not preclude a specific heart muscle disease related to diabetes, but suggest that these slightly raised blood pressures contribute significantly to left ventricular dysfunction in these patients, in whom the risk of cardiovascular disease is already greatly increased.

Full text

Br
Heart
J
1990;64:266-71
Abnormal
diastolic
function
in
patients
with
type
1
diabetes
and
early
nephropathy
M
J
Sampson,
J
B
Chambers,
D
C
Sprigings,
P
L
Drury
Department
of
Diabetes,
King's
College
Hospital,
London
M
J
Sampson
P
L
Drury
Department
of
Cardiology,
King's
College
Hospital,
London
J
B
Chambers
D
C
Sprigings
Correspondence
to
Dr
M
J
Sampson,
Diabetic
Clinic,
King's
College
Hospital,
Denmark
Hill,
London
SE5
9RS.
Accepted
for
publication
6
June
1990
Abstract
Left
ventricular
diastolic
function
was
assessed
by
pulsed
Doppler
echocardio-
graphy
in
non-diabetic
controls
(n=11)
and
in
patients
with
type
1
diabetes
with-
out
microvascular
disease
(n
=
16;
diabetic
controls),
with
microalbumin-
uria
(n
=
9),
or
with
early
persistent
proteinuria
(n=
11).
The
peak
filling
velocities
during
the
early
and
atrial
phases
of
left
ventricular
diastole
and
their
ratio
(E:A
ratio)
were
measured.
All
patients
with
diabetes
had
a
normal
serum
concentration
of
creatinine
and
exercise
electrocardiogram.
The
mean
E:A
ratio
was
significantly
lower
in
those
with
proteinuria
than
in
the
diabetic
controls
because
of
an
increase
in
peak
atrial
filling
velocity;
most
patients
with
proteinuria
had
an
abnormal
E:A
ratio
of
<
10.
Multiple
regression
analysis
showed
that
systolic
blood
pressure
was
the
major
determinant
of
both
the
peak
filling
velocity
during
the
atrial
phase
of
diastole
and
also
left
ventricular
mass.
Blood
pressures
were
significantly
higher
in
the
proteinuria
group
than
in
the
diabetic
controls.
Glycaemic
control
and
autonomic
function
did
not
influence
diastolic
filling.
The
slightly
raised
blood
pressures
at
the
earliest
stages
of
diabetic
nephropathy
are
sufficient
to
alter
left
ventricular
diastolic
compliance-this
may
reflect
early
hypertensive
heart
disease.
These
data
do
not
preclude
a
specific
heart
muscle
disease
related
to
diabetes,
but
suggest
that
these
slightly
raised
blood pressures
contribute
sig-
nificantly
to
left
ventricular
dysfunction
in
these
patients,
in
whom
the
risk
of
cardiovascular
disease
is
already
greatly
increased.
The
blood
pressure
begins
to
rise
at
the
earliest
stage
of
diabetic
nephropathy,'
and
left
ventricular
hypertrophy
(probably
related
to
hypertension)
is
common
once
renal
impairment
develops.2'
Abnormal
left
ven-
tricular
diastolic
function
may
be
the
earliest
echocardiographic
sign
of
hypertensive
heart
disease,56
often
occurring
before
appreciable
left
ventricular
hypertrophy
has
developed.
In
patients
without
diabetes,
hypertensive
left
ventricular
hypertrophy
is
an
independent
risk
factor
for
cardiovascular
morbidity
and
mortality.478
The
presence
of
blood
pressure
related
diastolic
abnormalities
at
the
earliest
stages
of
diabetic
nephropathy
might
identify
patients
likely
to
benefit
from
early
antihyper-
tensive
treatment.
Recently,
pulsed
Doppler
echocardiography
was
used
to
assess
diastolic
function.9
10
We
used
this
technique
to
investigate
the
pos-
sibility
that
the
slightly
raised
blood
pressure
associated
with
microalbuminuria
and
early
proteinuria
may
influence
left
ventricular
diastolic
function.
Patients
and
methods
PATIENTS
We
studied
39
white
patients
aged
20-60
with
type
1
diabetes.
They
were
selected
according
to
urinary
protein
excretion
and
not
according
to
blood
pressure.
None
had
evidence
of
renal
disease
other
than
diabetic
nephropathy
or
received
medication
other
than
insulin.
The
mean
albumin
excretion
rate
was
calculated
from
three
timed
overnight
urine
collections
taken
in
the
preceding
6-12
months.
The
following
groups
were
studied:
Diabetic Controls
Seventeen
patients
with
fewer
than
three
microaneurysms
in
each
eye
(on
dilated
fundoscopy
by
a
single
observer)
and
a
mean
albumin
excretion
rate
in
the
normal
range
(<
10
jug/min).
Microalbuminuria
Ten
patients
with
a
raised
mean
albumin
excretion
rate
of
between
30
and
200
ig/min.
Early
persistent
proteinuria
Twelve
patients
with
persistent
Albustix-positive
urine
samples
for
between
6
months
and
5
years,
a
24
hour
urinary
protein
loss
of
>
300
mg
(on
two
occasions),
and
a
normal
serum
creatine
(<
106
yimol/l).
None
of
these
patients
had
received
antihypertensive
treatment
before
the
study.
In
addition,
we
studied
11
non-diabetic
white
individuals
with
no
history
of
ischaemic
heart
disease
or
hypertension
and
on no
treat-
ment.
All
patients
gave
informed
consent
to
the
procedures,
which
were
approved
by
the
hos-
pital
ethics
committee.
Table
1
shows
the
clinical
features
of
the
groups.
The
mean
albumin
excretion
rate
was
66
M,g/min
in
the
diabetic
control
group
and
56-5
ig/min
in
the
microalbuminuria
group.
By
definition,
none
of
the
patients
in
the
diabetic
control
group
had
retinopathy
but
all
of
the
other
patients
with
diabetes
had
either
background
or
proliferative
retinopathy.
266

Diastolicfunction
in
early
nephropathy
Table
I
Clinicalfeatures
of
patients
studied
(mean
(I
SEM))
Group
Non-diabetic
Diabetic
Micro-
Feature
controls
controls
albuminuria
Proteinuria
n
11
16
9
11
Age
(yr)
34
(3)
35
(2)
38
(3)
34
(3)
Sex
(M:F)
6:5
9:7 5:4
8:3
Diabetes
duration
(yr)
-
20
(2)
23
(3)
23
(2)
Body
mass
index
(kg/m2)
24
7
(1)
25-3
(1)
26-9
(1)
25-7
(0-5)
Glycated
haemoglobin
(O)
-
8-8
(0(5)
10-6
(0
7)*
10-3
(0
6)
Blood
glucose
(mmol/l)
-
13-5
(1-4)
9-9
(1-7)
12-1
(1-8)
Systolic
pressure
(mm
Hg)
123
(4)
131
(4)
140
(6)
146
(2)t
Diastolic
pressure
(mm
Hg)
80
(4)
81
(2)
86
(3)
94
(3)t
Heart
rate
(beats/min)
78
(3)
84
(4)
88
(5)
92
(5)
HRV
(beats/min)
-
17-8
(2
3)
11-6
(2
8)
10-7
(1-5)
Valsalvaratio
-
152(0
1)
1
32(0-1)
1-35
(01)
HRR
(beats/min)
-
204
(3
9)
16
2
(2
8)
13-8
(2-3)
*p
<
0
05
v
diabetic
controls.
tp
<
0
001
v
diabetic
and
non-diabetic
controls.
HRV,
heart
rate
variability;
HRR,
heart
rate
response
to
standing.
METHODS
Glycated
haemoglobin
and
blood
glucose
were
measured
in
samples
taken
at
the
time
of
the
echocardiogram.
The
albumin
radio-
immunoassay
used
has
an
intra-assay
co-
efficient
of
variation
of
6%
at
an
albumin
concentration
of
2-5
mg/l
and
a
normal
range
for
non-diabetic
individuals
of
0-9-10
Mg/min.
Cardiovascular
autonomic
function
was
asses-
sed
in
the
patients
with
diabetes
by
the
heart
rate
responses
to
deep
breathing
at
6
breaths
per
minute,
to
standing,
and
to
the
Valsalva
manoeuvre."
The
Valsalva
ratio
was
not
measured
in
one
patient
in
each
of
the
proteinuria
and
microalbuminuria
groups
because
of
recent
vitreous
haemorrhages.
Autonomic
function
tests
were
performed
after
echocardiography.
Blood
pressure
was
measured
after
5
min-
utes'
supine
rest,
at
the
time
of
the
echo-
cardiogram,
by
an
observer
who
was
unaware
of
the
patient's
echocardiographic
data.
Three
readings
were
taken
with
a
Hawksley
random
zero
sphygmomanometer
(Lancing,
Sussex).
Korotkoff
phase
V
was
regarded
as
the
dias-
tolic
pressure.
Mean
values
for
systolic
and
diastolic
pressure
were
calculated.
No
patient
had
a
postural
systolic
fall
in
blood
pressure
of
more
than
10
mm
Hg
after
2
minutes
of
standing.
Bruce
protocol
treadmill
exercise
tests'2
were
performed
and
analysed
by
standard
criteria
for
ischaemia"
in
all
patients
with
diabetes,
but
not
in
the
normal
control
group.
One
diabetic
control
and
one
microalbumin-
uric
patient
had
unequivocally
abnormal
exer-
cise
tests'4
and
one
proteinuric
patient
had
a
borderline
abnormality
with
1
mm
planar
ST
segment
depression.
These
three
patients
were
excluded
from
the
study;
all
other
exer-
cise
tests
were
normal.
In
the
remaining
patients
the
mean
exercise
times
and
max-
imum
achieved
heart
rates
did
not
differ
be-
tween
groups.
All
echocardiograms
were
performed
and
analysed
by one
observer
(JBC),
who
was
unaware
of
the
patients'
clinical
state.
A
phased
array
system
(Hewlett-Packard
77020A,
Andover,
Massachusetts,
USA)
was
used
with
a
2-5
MHz
duplex
probe.
Sector
scans
with
colour
flow
mapping
were
used
to
screen
for
wall
motion
or
valvar
abnor-
malities;
these
were
absent
in
all
subjects.
Pulsed
Doppler
recordings
were
made
from
the
apical
four
chamber
approach,
with
the
sample
volume
level
with
the
tips
of
the
mitral
valve
leaflets
in
their
maximum
diastolic
extent.
We
measured
the
peak
left
ventricular
inflow
velocities
during
the
early
(E
vel)
and
atrial
(A
vel)
phases
of
left
ventricular
dia-
stolic
filling,
and
the
ratio
of
these
two
filling
velocities
(E:A
ratio;
fig
1).
Mean
values
for
each
of
these
variables
were
calculated
from
10
cardiac
cycles
to
allow
for
respiratory
variations.
Chamber
dimensions
and
left
ventricular
thickness
were
calculated
from
M
mode
echocardiograms
recorded
according
to
American
Society
of
Echocardiography
recommendations.'4
Measurements
of
the
intraventricular
septal
and
posterior
walls
were
plotted
on
age
and
body
mass
related
nomograms,'4
and
were
considered
to
be.
increased
if
they
lay
above
the
relevant
95th
centile.
Left
ventricular
mass
index
was
cal-
Figure
I
Pulsed
Doppler
echocardiograms
recorded
in
a
diabetic
patient
without
microvascular
complications
showing
the
early
passive
peak
in
left
ventricularfilling
(E)
and
the
later
active
atrial
phase
(A).
The
right
hand
echocardiogram
shows
reversal
of
this
pattern
in
a
diabetic
patient
with
proteinuria
and
mild
hypertension.
I'
E
E
mm_f
-
.
A
A
E
,,,
A
E:
4
.
k.4
'
)OA
A;
M~~~~~~~~~~~~~~~~~~:
M.
-
W
26o7
a a

Sampson,
Chambers,
Sprigings,
Drury
culated
from
the
method
described
by
Devereux
and
Reichek'5
and
left
ventricular
end
diastolic
volume
from
the
Teicholz
for-
mula.
STATISTICAL
ANALYSIS
The
groups
were
initially
compared
by
one
way
analysis
of
variance.
Unpaired
Student's
t
tests
were
performed
if
a
significant
(p
<
0
05)
difference
was
found
by
analysis
of
variance.
Simple
and
stepped
multiple
regres-
sion
analysis
were
used
with
A
vel,
E
vel,
the
E:A
ratio,
and
left
ventricular
mass
as
depen-
dent
variables.
Systolic
and
diastolic
blood
pressures,
age,
heart
rate,
ventricular
mass,
left
ventricular
fractional
shortening,
glycated
haemoglobin,
blood
glucose,
and
individual
measures
of
autonomic
function
were
included
as
subjective
variables.
Significance
was
taken
to
be
p
<
0
01
for
multiple
regres-
sion.
Fisher's
exact
test
was
used
where
appropriate.
All
data
are
shown
as
mean
(1
SEM).
Results
BLOOD
PRESSURE,
HEART
RATE,
AND
GLYCAEMIC
CONTROL
Blood
pressure
did
not
differ
significantly
between
the
control
groups
(table
1).
Mean
systolic
and
diastolic
blood
pressures
increased
progressively
from
both
control
groups
to
the
proteinuria
group
and
were
significantly
higher
in
the
latter
(p
<
0
001).
There
was
no
significant
difference
in
mean
heart
rate
or
blood
glucose
between
the
groups,
although
the
mean
concentration
of
glycated
haemo-
globin
was
significantly
higher
in
the
micro-
albuminuria
group
than
in
the
diabetic
con-
trols.
AUTONOMIC
FUNCTION
Mean
heart
rate
variability,
the
Valsalva
ratio,
and
heart
rate
response
to
posture
tended
to
be
lower
in
the
microalbuminuria
and
proteinuria
groups,
but
this
trend
was
not
significant
(table
1).
None
of
the
patients
studied
had
symp-
tomatic
autonomic
neuropathy
and
only
one
patient
in
each
group
had
abnormalities
in
all
three
tests
of
autonomic
function.
None
had
a
postural
systolic
fall
in
blood
pressure
of
>
10
mm
Hg.
PULSED
DOPPLER
MEASUREMENTS
Mean
E
vel
did
not
differ
significantly
between
groups,
but
mean
A
vel
was
significantly
higher
in
the
proteinuria
group
than
in
the
control
groups
(p
<
0-005)
(fig
2).
This
led
to
a
significantly
lower
E:A
ratio
in
the
proteinuria
group
than
in
both
control
groups
(p
<
0-05).
Three
(18-80,)
diabetic
controls
had
an
E:A
ratio
below
10
(fig
3)
compared
with
four
(44%0)
of
nine
in
the
microalbuminuria
group
(p
>
0-1)
and
seven
(640')
of
11
in
the
proteinuria
group
(p
<
0
05).
Seven
of
the
14
patients
with
an
abnormal
E:A
ratio
had
mild
intraventricular
septal
hypertrophy,
and
the
intraventricular
septum
was
significantly
wider
in
the
microalbuminuria
and
proteinuria
groups
than
in
the
control
groups
(table
2).
Left
ventricular
fractional
shortening
was
higher
in
the
proteinuria
group
than
in
the
non-diabetic
controls
(p
<
0001),
as
was
mean
left
ven-
tricular
mass,
but
not
significantly
so.
RELATION
BETWEEN
MEASUREMENTS
Table
3
shows
the
results
of
simple
linear
regression.
Multiple
regression
showed:
(a)
E
vel
was
only
independently
influenced
by
age
(R2=
13.500;
F1,45=70;
p
<
005;
NS).
Figure
2
Values
for
peak
left
ventricular
early
filling
(A)
and
atrial
filling
velocity
(B)
in
normal
controls
and
in
the
three
diabetic
groups.
In
A
there
is
an
overlap
of
some
values
for
the
diabetic
controls
and
patients
with
proteinuria.
11.I
1.0.
0.9
0.8
_
07
E
0.6
w
0o5
0-3
0.2
0.1
*
S
.
*
I
.
S
S
.
.
1.2
I.'
0
S
1.0
*
*
0-9
S
e
0.8
S
0
-~~~~
0-
67
5
VI
I
>4
0
*
<40.5-
S
*
0.j-
v-_
03-
0-2-
0.
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-
0
0
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0
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t
as
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r
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30
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268

Diastolic
function
in
early
nephropathy
Table
2
Echocardiographic
data
(mean
(1
SEM))
Group
Non-diabetic
Diabetic
Micro-
controls
controls
albuminuria
Proteinuria
Variable
(n=
11)
(n=
16)
(n=
9)
(n=
11)
E
vel
(m/s)
0
74
(0
1)
0
74
(0
03)
0-69
(0
07)
0-76
(0-06)
A
vel
(m/s)
0-56
(0-03)
0-63
(0
03)
0-67
(0-07)
0-78
(0
03)*
E:A
ratio
1-42
(0
1)
1
21
(0
08)
1-08
(0
1)
0-98
(0-06)t:
Diastolic
dimension
(mm)
47
(1)
47
(1)
48
(1)
47
(2)
End
diastolic
volume
(ml)
102(4)
113
(6)
109
(8)
111(9)
Septal
width
(mm)
9-7
(0-07)
9-8
(0.04)
11
7
(0
07)*
11
9
(0
08)*
LV
mass
(g/m)
87(8)
101
(5)
115(8)
113(9)
Fractional
shortening
(%)
29
(2)
35
(2)
36
(3)
38
(2)§
*p
<
0-005,
diabetic
and
non-diabetic
controls;
tP
<
0-05,
v
diabetic
controls;
tp
<
0-0001,
v
non-diabetic
controls;
§p
<
0-001,
v
non-diabetic
controls.
E
vel
and
A
vel,
peak
early
and
atrial
diastolic
filling;
E:A
ratio,
E
vel/A
vel;
LV,
left
ventricular.
Table
3
Significant
correlation
coefficients
(r)
and
probability
values
(p)
where
E
vel,
A
vel,
and
the
E:A
ratio
are
dependent
variables
in
simple
linear
regression
E
vel
A
vel
E:A
Variables
r
p
r
p
r
p
Age
-0-46
0
001
-
0-36
0
05
Heart
rate
-
0-42
0005
0-42
0005
Systolic
blood
pressure
-
053
0-0001 0-48
0.001
Diastolic
blood
pressure
-
-
-
Ventricular
mass
-0-37
0
05
Duration
of
diabetes
-
-
Fractional
shortening
-
0
34
0-05
End
diastolic
volume
-
-
-
Glycated
Hb
-
-
-
Blood
glucose
-
-
-
Heart
rate
variability
-
-
-
Valsalva
ratio
-
-
-
Heart
rate
response
-
-
-
2.2-
2-0-
1.8-
1-61
1.4-
0
1.2
cs-
1.0-
0-8-
0.6-
0-2-
0
0
0
%
0
0
*
0
0
*
0*
*
U--
- - ----
.
..
.
.
.
.
.I
#
.
0
N.D
(b)
A
vel
was
most
influenced
by
systolic
blood
pressure
(R2=28%;
F1,45=17-4;
p
<
0-0001)
(fig
4)
but
also
by
heart
rate
(R2=
8-6%;
F,44
=60;p
<
005;NS).
(c)
The
E:A
ratios
were
only
independently
influenced
by
age
and
heart
rate
(R2=
38/%;
F2,44=13-6;p
<
0-0001).
1.2-
1.1
1.0
0.9
0.8
-%
0-7
E
r
0.6
0-
0.5.
0.3-
0.2-
0-1
o-
o
M
+
(a
en
00
+
°
+
Non-dicabetic
controls
o
Diabetic
controls
o
Microcilbuminura
*
Proteinurica
-a
-----
.
*
80
100
120
140
160
180
Systolic
blood
pressure
(mmHg)
200
Figure
4
Relation
between
systolic
blood
pressure
and
the
peak
atrial
phase
of
left
ventricular
diastolic
filling
(A
vel)
in
the
total
study
population
(r=
0
53,
p
<
0O0OO1,
n=47).
(d)
The
ventricular
mass
was
only
influ-
enced
by
systolic
blood
pressure
(R2
=
21
%;
F,,45=12
1;p
<
0-001).
There
was
no
significant
relation
between
any
measure
of
cardiovascular
autonomic
func-
tion
or
glycaemic
control
and
diastolic
filling.
Discussion
We
have
shown
that
the
left
ventricular
filling
pattern,
as
assessed
by
the
E:A
ratio,
may
be
abnormal
in
the
earliest
stages
of
diabetic
nephropathy-even
if
left
ventricular
hyper-
trophy
is
not
considerable.
The
reduced
E:A
ratio
was
the
result
of
an
increased
atrial
component
of
diastolic
filling,
and
systolic
blood
pressure
was
the
principal
influence
on
this
measurement
and
also
on
left
ventricular
mass.
Only
E:A
ratios
<
1-0
show
an
association
with
a
reduced
left
ventricular
filling
rate
on
angiography9
and
the
significance
of
small
changes
is
unclear.
Furthermore,
left
ven-
tricular
diastolic
filling
is
influenced
by
several
factors.
Regional
phase
delays
in
ventricular
relaxation,
a
raised
left
atrial
pressure,
altera-
tions
in
preload,"6
the
contractile
state
of
the
left
ventricle,'7
and
cardiovascular
autonomic
dys-
function'8
may
all
influence
diastolic
filling
without
any
true
change
in
left
ventricular
compliance.
In
the
present
study,
however,
the
cardiac
valves,
wall
motion,
and
left
ventricular
end
diastolic
volumes
were
normal
in
all
patients
or
did
not
differ
between
groups.
Though
left
ventricular
fractional
shortening
was
higher
in
the
group
with
proteinuria
than
in
the
normal
controls,
on
multiple
regression
this
variable
did
not
contribute
significantly
to
any
pulsed
Doppler
measurement.
Finally,
cardiovascular
autonomic
function
had
no
influence
on
diastolic
filling.
Therefore,
the
differences
in
E:A
ratio
shown
in
this
study
almost
certainly
reflect
differences
in
left
ven-
tricular
compliance.
Left
ventricular
compliance
depends
on
chamber
size
and
geometry,
wall
thickness,
and
the
mechanical
properties
of
cardiac
muscle."9
Figure
3
Values
for
the
E:A
ratio
in
normal
controls
and
the
three
diabetic
groups.
l.
i
269
.

Sampson,
Chambers,
Sprigings,
Drury
In
this
study
systolic
blood
pressure
was
the
principal
correlate
of
left
ventricular
mass,
and
the
mild
hypertension
present
in
very
early
nephropathy
could
affect
the
mechanical
properties
of
the
ventricle
without
significantly
increasing
left
ventricular
mass.
There
is
sup-
portive
evidence
from
experimental
hyper-
trophy
caused
by
pressure
overload
in
rats
that
such
changes
in
ventricular
compliance
can
occur
independently
of
changes
in
ventricular
wall
thickness
or
mass.'2
These
changes
in
the
mechanical
properties
of
the
left
ventricle
could
then
presumably
influence
the
pattern
of
left
ventricular
diastolic
filling.
The
patients
with
proteinuria
had
borderline
hypertension
(mean
blood
pressure
146/94
mm
Hg);
and
diastolic
function
is
often
abnormal
in
non-diabetics
with
borderline
essential
hyper-
tension.56
An
isolated
increase
in
the
peak
atrial
component
of
diastolic
filling
is
also
well
des-
cribed
in
such
patients3
2223
and
is
often
present
before
significant
left
ventricular
hypertrophy
develops.
An
increased
atrial
contribution
to
diastolic
filling
in
patients
with
diabetes
has
also
been
described24
25
as
has
a
relation
between
the
sytolic
blood
pressure
and
diastolic
function
in
those
with
type
1
diabetes.26
However,
it
is
unclear
in
these
studies
whether
there
is
any
relation
between
the
diastolic
abnormalities
and
blood
pressure2425
or
whether
the
abnor-
malities
are
confined
to
a
subgroup
with
mild
hypertension.26
There
have
been
many
other
studies
on
diastolic
function
in
diabetes,
and
many
are
difficult
to
interpret
because
the
data
on
blood
pressure,
ischaemic
heart
disease,
or
renal
function
are
frequently
incomplete.27"3
However,
diastolic
function
was
abnormal
in
normotensive
patients
with
type
1
diabetes,
without
apparent
coronary
artery
disease,32-34
raising
the
possibility
of
a
specific
heart
muscle
disease
in
diabetes.
The
concept
of
such
a
"diabetic
cardiomyopathy"
was
initially
sup-
ported
by
epidemiological
studies35
that
showed
an
increased
incidence
of
congestive
heart
failure
among
the
diabetic
subjects
in
the
Framingham
cohort,
although
much
of
this
could
be
accounted
for
by
an
excess
of
occult
ischaemic
heart
disease.
A
series
of
necropsy
studies,
generally
in
those
with
type
2
diabetes,3638
many
with
renal
impairment
who
had
died
in
cardiac
failure,
are
often
used
to
support
the
existence
of
a
specific
diabetic
heart
muscle
disease.
The
commonest
patho-
logical
findings
in
these
studies-an
increased
left
ventricular
mass,
left
ventricular.
hyper-
trophy,
and
increased
interstitial
and
perivas-
cular
fibrosis,
could
equally
well
reflect
preced-
ing
hypertension3940
or
more
severe
hyperten-
sion
in
the
diabetic
group.36
Most
non-invasive
studies
on
patients
with
diabetes
have
since
failed
to
describe
cardiac
structural
changes
in
the
absence
of
hypertension,34
41
42
and
the
results
of
myocardial
biopsy
studies
in
patients
with
diabetes
are
conflicting.435
However,
some
data
do
suggest
an
increase
in
myocardial
connective
tissue
in
patients
with
diabetes
without
hypertension
or
coronary
artery
dis-
ease,45
and
this
could
theoretically
influence
diastolic
compliance.'
The
question
of
a
specific
diabetic
heart
muscle
disease
requires
a
large
correlative
study
of
myocardial
histopath-
ology
with
both
invasive
and
non-invasive
assessment
of
cardiac
function
in
well
defined
groups
without
coronary
artery
disease,
hyper-
tension,
or
microvascular
disease.
Finally,
we
did
not
find
any
relation
between
diastolic
filling
and
autonomic
function
in
our
patients,
in
contrast
with
the
findings
of
other
groups.'847
These
groups
showed
that
abnor-
mal
diastolic
filling
measured
by
radionuclide
ventriculography'8
or
digitised
M
mode
echocardiography47
was
related
to
the
degree
of
postural
fall
in
systolic
blood
pressure,'8
and
less
so
to
measurements
of
heart
rate
vari-
ability.'847
In
view
of
the
preload
dependence
of
diastolic
filling,'6
some
of
the
abnormalities
described
by
these
groups
could
be
related
to
a
reduced
preload
associated
with
postural
hypotension.
Other
studies
have
failed
to
des-
cribe
any
relation
between
autonomic
and
diastolic
function
in
patients
with
diabetes"
or
have
failed
adequately
to
correct
for
the
high
heart
rate
associated
with
autonomic
neuropathy.25
In
conclusion,
we
showed
that
in
patients
with
type
1
diabetes,
diastolic
function
is
significantly
abnormal
in
most
patients
by
the
stage
of
very
early
proteinuria.
These
abnor-
malities
may
be
related
to
the
mild
hyperten-
sion
seen
in
these
patients.
The
present
results
do
not
preclude
the
existence
of
a
specific
diabetic
heart
muscle
disease,
but
the
presence
of
diastolic
dysfunction
(related
in
part
to
the
raised
blood
pressure)
at
such an
early
stage
of
nephropathy,
as
well
as
mild
left
ventricular
hypertrophy'
re-emphasises
the
case
for
early
antihypertensive
treatment
in
these
patients
and
for
the
increased
use
of
echocardiography
to
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those
at
risk.
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M,
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