Download Changes in Blood Pressure, Body Fluids

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Clinical Science (1982) 6 3 , 4 1 5 4 1 8 s
Changes in blood pressure, body fluids, circulating angiotensin
I1 and aldosterone, with improved diabetic control
J. A. O ’ H A R E , J. B. F E R R I S S , B. M. T W O M E Y * , H . G O N G G R I J P A N D
D. J . O’SULLIVAN
Departments of Medicine and *Medical Physics, Regional Hospital and University College, Cork, Ireland
Summary
Introduction
1. We studied 12 normotensive non-ketotic
diabetic patients during poor metabolic control,
with sustained hyperglycaemia, and again, after
an interval of 3 weeks, when metabolic control
was improved. On each occasion we measured
blood pressure, total exchangeable sodium,
plasma volume, transcapillary escape rate of
albumin, and plasma concentrations of angiotensin 11 and aldosterone.
2. With improved diabetic control there was a
small but significant fall in arterial pressure. Total
exchangeable sodium was normal when control
was poor but rose significantly to above normal
with improved control.
3. Plasma volume also rose significantly with
improved control, and the transcapillary escape
rate of albumin fell and the intravascular mass of
albumin rose.
4. Plasma angiotensin I1 and aldosterone
concentrations were significantly above normal
during poor metabolic control, but fell to normal
with improved control.
5. These findings indicate a resetting of the
relationship between blood pressure and exchangeable sodium when diabetic control
improves. The association between exchangeable
sodium and concentrations of angiotensin I1 and
aldosterone also appears altered in diabetic
patients. These changes associated with varying
metabolic control must be considered when
studying cardiovascular disease in diabetic
patients.
Epidemiological studies [ 11 suggest that newly
diagnosed diabetic patients have higher blood
pressures than established treated diabetic
patients, and an independent positive relationship
has been observed between blood pressure and
blood glucose, both in adults [ 1I and in children
[21. However, there is little available information
on the effects of changing diabetic control on
blood pressure and body fluid volumes in nonketotic diabetic patients. There have been conflicting clinical [3, 41 and experimental 15, 61 reports
on the influence of varying diabetic control on the
renin-angiotensin-aldosterone system. We investigated the simultaneous effects of improved
diabetic control on blood pressure, total
exchangeable sodium, plasma volume, transcapillary escape rate of albumin, plasma angiotensin XI and aldosterone, in non-ketotic diabetes
mellitus.
Key words: albumin, aldosterone, angiotensin 11,
diabetes, plasma volume, sodium.
Correspondence: Dr J. A. O’Hare, Clinical Investigation Unit, Regional Hospital, Cork, Ireland.
Methods
We studied 12 diabetic patients (nine male),
whose mean age was 54 years (range 27-73
years). The three women were postmenopausal.
Six were newly diagnosed and six were known
diabetic patients whose mean duration of diabetes
was 6.7 years (range 1-19 years). Nine patients
had maturity-onset (type 11) diabetes and three
had juvenile-onset (type I) diabetes. Eight
patients were treated by diet and oral
hypoglycaemic agents, and four were treated by
diet and insulin. Three patients had diabetic
polyneuropathy and two of these had background retinopathy. None had significant proteinuria and d had normal plasma urea and
creatinine. None had cardiac or liver disease and
none was on treatment other than that for
diabetes.
J . A . O'Hare et al.
416s
Patients were first studied while in poor
diabetic control. All had recent thirst and polyuria, but none had ketonuria. Diabetic control
was improved by dietary measures, together with
oral hypoglycaemic agents (n = 8) or insulin
therapy (n = 4). The patients were then discharged from hospital and readmitted for repeat
studies an average of 3 weeks (range 2-6 weeks)
later. All patients were admitted to a metabolic
ward and intake sodium and potassium was
unrestricted during each study period.
Blood pressure was measured supine, after
overnight rest, between 09-00 and 10.00 hours on
the second hospital day, with a London School of
Hygiene sphygmomanometer. Blood pressure
values reported are the means of five measurements taken over a 20 min period (diastolic phase
9, before venepuncture. Mean arterial pressure
was calculated from the diastolic plus one-third of
the pulse pressure. Diabetic control was assessed
from Hb A, measurements and a 24 h (five
sample) blood glucose profile. A fall in both
Hb A,, fasting and mean 24 h blood glucose was
required for an improvement in diabetic control.
Total exchangeable sodium was measured by the
24Nadilution technique with correction for urinary
loss, and results were expressed both in absolute
terms and as the % predicted by the leanness
index 171,derived from a control population of 33
non-diabetic patients. Plasma volume, transcapillary escape rate of albumin and intravascular mass of albumin were measured as
previously described 181. Blood volume was
calculated from a corrected packed cell volume.
Plasma angiotensin I1 191 and aldosterone 1101
were measured by radioimmunoassay. Statistical
, analyses were performed by paired and unpaired
'Student's t-test as appropriate.
Results
The changes that occurred with improved
diabetic control are summarized in Table 1. There
was a highly significant fall in HbA,, fasting
blood glucose and in mean 24 h blood glucose,
with improved control. There was also a small but
significant fall in both systolic and diastolic
arterial pressures. Total exchangeable sodium
was normal during poor control, but rose to levels
significantly above normal with improved control.
Plasma volume rose and packed cell volume fell
significantly with improved control. Transcapillary escape rate of albumin fell, whereas
plasma albumin concentration and intravascular
mass of albumin rose significantly with improved
control.
T , w u 1. Mean values of variables measured when diabetic control was poor and when metabolic control improved, together
with valuesfor normal subjects studied under the same conditions.
Mean values &
SEM
are shown.
P < 0.02; ** P < 0.01; *** P < 0401,
when compared with normal controls. N.S., N o t
significant. n, Number of patients studied.
Diabetic patients
Fasting blood glucose (mmol/l)
Mean 24 h blood glucose (mmol/l)
Hb A ,
Blood pressure
systolic
diastolic
mean
Plasma angiotensin 11 (supine) (pmol/l)
Plasma aldosterone (supine) (pmol/l)
Total exchangeable sodium (mmol)
Total exchangeable sodium (% predicted)
Serum sodium (mmol/l)
Serum potassium (mmol/l)
Plasma volume (mVl.73 m*)
Packed cell volume (%)
Blood volume (mVl.73 m')
Transcapillary escape rate of albumin (%/h)
Plasma albumin (g/l)
lntravascular mass of albumin (g/1.73 m2).
Body wt. (kg)
24 h urine sodium excretion (mmol)
24 h urine potassium excretion (mmol)
Normal
subjects
Poor
control
Improved
control
n
P
13.9 t 1 . 1
16.5 f 0 . 9
12.4 f 0.5
7.2 f 0.7
8 . 0 f 0.5
9.3 f 0.3
I2
I2
I2
t0.001
<O.oOl
121.8 f 4.7
71.8 f 2.3
88.4 f 2.6
15.7 f 3.2
525.2 f 72.0
3196.0 f 105.0
106.0f 1.3.'
138.2 f 0 . 7
3.9 f 0. I
3102.0 +_ 145.3
38.4 ? 1 . 1
4 8 1 4 . 0 f 221.0
6.8 f 0.9
37.8 f 1.2
118.3 f 10.6
71.0t3.1
131.0f 14.6
50.0 f 0 . 3
12
12
I2
12
<0.02
<0.05
(0.02
t0.02
t0.02
<0.01
124.8 f 5.4
76.2 f 2.3
92.6 f 3. I
36.3 f 9.0.
812.2 f 56.6***
3103.0f 111.7
102.6 k 1.2
133.8 f 0.6..
4.120.1
2860.0 f 122.4
41.3 f 1.2
4616.0 f 207.0
9.2 f 1.1"
35.8 f 0 . 9
102.9 f 8.5
70.5 ? 3.1
109.0 f 14.6
52.0 f 0 . 2
10
9
9
12
I2
II
12
II
8
I2
II
I2
10
10
t0.001
<0.01
to.001
t0.05
10.05
<0.005
N.S.
<0.01
t0.05
10.01
N.S.
N.S.
N.S.
n
-
120.3 f 1 . 7
72.4 t 1.4
88.9 f 1.3
14.9 c 5.0
422.4 f 29.5
2967.1 f 93.0
100.0 c 1.8
139.2 f 0 . 4
4 . 0 f 0. I
2887.0 ?r 141.0
40.0 t 0 . 6
4684.0 5 232.0
5.7 f 0.7
36.2 f 1.0
104.3 f 5 . 5
69.4 i 2 . 6
119.8 i 10.7
42.1 f 3.6
33
33
33
36
31
33
33
33
28
14
14
14
II
14
14
33
26
26
Diabetic control
Mean concentrations of plasma angiotensin I1
and aldosterone were significantly higher than
normal during poor control, but fell to normal
levels with improved control. Serum sodium rose
and serum potassium fell with improved control.
Body weight and urinary 24 h sodium and
potassium excretion did not change significantly.
Discussion
There was a small but significant fall in blood
pressure with improved diabetic control in these
patients. The present study cannot exclude
influences on blood pressure other than those
produced by changes in diabetic control. Should
the fall in blood pressure with improved control
be confirmed, however, this would have important
implications. Higher blood pressures, associated
with poor control, may not only accelerate
atheroma formation [ 1 11 but also hasten the
development of specific microvascular complications of diabetes [12, 131. Blood pressure
decreased with improved control despite a rise in
plasma volume and in total exchangeable sodium.
However, plasma angiotensin I1 concentrations
fell, and changes in sympathetic activity and
other unidentified factors may have contributed
to the blood pressure fall.
Total exchangeable sodium rose with improved
control, an observation in keeping with a previous
balance study showing sodium retention after
insulin treatment [ 141. The increase in exchangeable sodium when control improved is in keeping
with previous observations in metabolically stable
diabetic patients [15, 161. This rise in exchangeable sodium may be mediated by an increase in
circulating insulin, which has a direct sodiumretaining effect on the diabetic kidney [17, 181.
The rise in plasma volume with improved
metabolic control is in keeping with a previous
report, which takes account of varying capillary
permeability [ 191 but contrasts with earlier
reports 12, 201. The fall in the transcapillary
escape rate of albumin with improved control is
also in keeping with a previous study [191 which
showed an increased transcapillary escape rate
with short-term deterioration of diabetic control.
This fall in transcapillary escape rate, together
with the rise in the intravascular mass and
concentration of albumin, is likely to favour the
increase in plasma volume. This and the rise in
exchangeable sodium may contribute to
suppression of the renin-angiotensin system with
improved control.
The elevated levels of plasma angiotensin I1
and aldosterone in poorly controlled diabetes are
in keeping with our previous findings [4, 211. It
417s
seems unlikely that these were the result of
sodium depletion, as exchangeable sodium was
normal in poorly controlled diabetic patients.
Plasma and blood volume were not decreased in
this study, although other stimuli to renin
secretion, such as increased sympathetic nervous
activity 1221 or total body potassium depletion
[231 may have been active during poor diabetic
control. When metabolic control improved and
exchangeable sodium rose above normal, angiotensin I1 and aldosterone concentrations fell to
normal, but not below. These findings indicate an
altered relationship between exchangeable sodium
and both angiotensin I1 and aldosterone in
diabetic patients. The reported changes with
varying diabetic control must be borne in mind
when studying cardiovascular abnormalities in
diabetic patients.
Acknowledgments
This study was supported by a grant from the
Medical Research Council of Ireland. We thank
Dr J. J. Morton of the MRC Blood Pressure Unit,
Western Infirmary, Glasgow, Scotland, for a gift
of angiotensin I1 antibody and the NIAMDD,
National Institute of Health, Bethesda, U.S.A. for
anti-aldosterone serum. We gratefully acknowledge the technical assistance of Miss Mary
Holmes.
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