Electrocardiographic Changes after Glucose
Ingestion
By LEON D. OSTRANDER, JR., M.D.,
AND
HEALTH appraisals involving multiple
laboratory studies are becoming increasingly common both in private practice and in
surveys conducted by industry, public health
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be classified as "abnorm,al." 4 6, 7-9 Indeed,
some workers have recommended postprandial electrocardiograms as a diagnostic tool in
the detection of occult coronary heart disease.6 8, 9 Such glucose or food induced electrocardiographic changes have also been described as misleading and of no significance.10
In previous studies, excepting those of
Simonson and co-workers employing the test
meal,3' 5, 6 postprandial electrocardiographic
changes have not been expressed in quantitative terms and in none have the electrocardiograms been classified by a standard
coding system.
groups, and epidemiologists. Electrocardiograms and tests of glucose tolerance are usually included. These tests vary in the amount
of glucose and the time interval at which
the blood specimen is drawn, but usually
either 50 or 100 Gm. of glucose are administered and the specimen is taken after 60 or
120 minutes.
Since there is a period of an hour or more
between glucose administration and the withdrawal of the blood specimen, this interval
could be used for other parts of the examination such as the electrocardiogram. This has
been the practice in at least one large sur-
Table 1
Minnesota Code for ST-Segment and T-Wave
Changes
vey.'
The literature,2-10 however, suggests that
electrocardiograms are altered sufficiently by
food or glucose to make postprandial tracings
deceptive. Most investigators, utilizing either
a standard test meal or a measured quantity
of glucose, report postprandial changes in
heart rate, ST-segment levels, and T-wave
amplitudes.2 While very slight depression
of ST segments and decreases in T waves
have been noted in the electrocardiograms
of most normal subjects, their postprandial
tracings remained in the broad range of
normality.3' On the other hand, subjects
with coronary heart disease but normal fasting electrocardiograms sometimes developed
sufficiently marked postprandial changes to
IV S-T junction and segment (measured from preceding PR segment at onset of QRS)
Depression:
1. S-T-J depression 1 mm. or
more
.I, II, aVL,
aVF, Vl-V6
2. S-T-J depression 0.5-0.9 mm.
and ST segment horizontal
or downward sloping I, II, aVL, aVF, V1-V6
3. No S-T-J depression as much
as 0.5 mm. but ST segment
sloping down and reaching
0.5 mm. or more below PR
I, II, aV L, aVF, V1-V6
segment ......
V T-wave items
1. T amplitude = minus 5 mm. or
V2-V6
ore
when R amplitude = 5 mm.
......... aVL
.. aV.
when QRS mainly upright ....
2. T amplitude = minus 1-5 mm.
I, II, V2-V6
when R amplitude = 5 mm.
......... aVL
or more ....
when QRS mainly upright .
aVE
3. T wave flat or small diphasic
(negative phase) less than 1 mm. I, II, V3-V6
when R amplitude= 5 mm.
or more ....
From the Department of Epidemiology, School of
Public Health, and the Department of Internal Medicine, Medical School, University of Michigan, Ann
Arbor, Michigan.
Supported in part by Program Project Grant HE06378 from the National Heart Institute, National
Institutes of Health, U. S. Public Health Service.
Circulation, Volume XXX, July 1964
BELSON JACK WEINSTEIN, M.D.
or
more
...
aVL
when QRS mainly upright ........... aVF
67
OSTRANDER, WEINSTEIN
68
Table 2
ST-Segment and T-Wave Changes * after Glucose Ingestion
Subjects without
apparent
heart disease; :NX 30
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Number with
ST-segment
changes
Mean ST
segment change,t
+ S.D. (mm.)
Range of
ST-segment
changes (mm.)
Number with
T-wave
changes
Mean T wave
change
S.D. (mm.)
Range
T-wave
change (mm.)
+-
not receiving digitalis; N_ :12
10
28
-1.1
Subjects with
coronary heart disease
Subjects with
coronary heart disease
receiving digitalis; N = 1 1
11
-0.5
1.2 ± 1.7
1.1
+ 1.5 to
+ 1.5 to -3.5
-
1.3
+ 1.0 to
3.5
-
2.5
30
10
11
-9.7 ± 5.5
- 3.1±4.0
-6.7 ± 2.8
-3.5 to -28.5
+ 3.0
to
-
-4.0 to - 9.5
10.5
*
These changes represent the means of the algebraic sums of
served in leads I, LI, aVL, aVF, and V2-V6.
t ST-segment changes do not include isolated junctional changes.
the individual
changes ob-
Table 3
Heart Rate Change after the Oral Administration of Glucose
Rate during
fasting state
Mean
(beats /'min.)
Range
Number
of
subjects
Number
with
Number
with
after faster rate
glucose after glucose
slower
rate
30 min.
Mean increase in rate
after glucose
60 min.
90 min.
120 min.
Without heart
disease; N = 30
With coronary
69.5
56-88
6
24
5.1
2.5
4.4
4.1
heart
disease; N
78.1
57-100
7
16
4.5
3.3
3.6
2.8
The
=
23
of this investigation is to
the ST-segment and T-wave
changes after oral glucose in hospitalized patients with and without manifest coronary
heart disease and to code the electrocardiograms in a uniform manner.
purpose
quantitate
Methods
Fifty-three ambulatory male medical inpatients at the Ann Arbor Veterans Administration Hospital were studied; all but one were
white. Thirty men, age 22 to 66 years (mean
age 46 years) had Ino evidence of heart disease
by history, physical examination, electrocardiogram, or chest x.ray, but were hospitalized for
other conditions. Twenty-three men, age 39 to
86 years (mean age 61 years), had coronary
heart disease as evidenced by angina pectoris,
myocardial infarction, or previous congestive
heart failure without other apparent cause; 11 of
these patients were receiving digitalis.
Subjects were prohibited from eating, drinking, or smoking after midnight before the test.
In the morning, a fasting blood specimen and
electrocardiogram were taken, and 100 Gm. of
glucose in 240 ml. of cool water were administered. Blood samples and electrocardiograms
were then taken at 30, 60, 90, and 120 minutes
after glucose ingestion. During this period the patients were allowed to lie or sit quietly or go to the
bathroom but were not allowed to eat, drink,
or smoke.
Circulation,
Volume
XXX, July 1964
ELECTROCARDIOGRAPHIC CHANGES AFTER GLUCOSE
69
Table 4
Relation between Variations in Heart Rate and Changes in ST-Segment Elevation, T-Wave Amplitudes
and Classification by "Minnesota Code"
Subjects without apparent heart disease
N = 30
Mean rank-ST* Mean rank-T wavet Minnesota Codet
10.0
15.7
20.8
A
B
C
2
1
0
14.2
12.8
19.5
Subjects wtih coronary heart disease
N = 23
Mean rank-ST* Mean rank-T wavet Minnesota Codet
7.7
14.0
14.5
4
3
l
12.9
12.3
10.7
A Tertile with greatest increase in heart rate after glucose ingestion.
B Tertile with medium increase in heart rate after glucose ingestion.
C Tertile with least increase in heart rate after glucose ingestion.
* Mean rank in degree of ST-segment depression for each tertile, the subjects with the greatest ST depression
having the highest rank and thus the lowest number.
t Mean rank in decrease of T-wave amplitude.
t Number of changes in "Minnesota" classification of ST-segment or T-wave items.
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Table 5
Changes in Class IV and V Items of "Minnesota Code" after Glucose Ingestion
ST-segment and T-wave changes
After glucose
Fasting
Subject without
apparent heart
disease; N = 3
Subjects with
coronary heart
disease receiving
digitalis; N = 5
Subjects with
coronary heart
disease not receiving
digitalis; N = 3
*
See Blackburn and
0
IV-2
IV-3
IV-3
IV-3
IV-3
V-3
V-3
V-3
IV-2, V-3
IV-2
IV-2
IV-2, V-2
IV-2, V-3
IV-2, V-2
V-3
IV-2, V-2
IV-1, V-2
V-2
0
0
0
0
0
0
0
I-3b, II-1
0
0
0
0
0
I-Id
associates.11
The electrocardiograms were recorded on a
direct-writing instrument at a paper speed of 25
mm. per second. The 'Minnesota Code" of
Blackburn and associates"1 (table 1) was used
to classify the ST-segment and T-wave characteristics of each electrocardiogram. In addition, STsegMent deviations from the PR segment at the
onset of QRS were measured to the nearest 0.5
mm. in leads I, It, aVL, aVF, and V2-V6,
and the algebraic sum of these deviations was
calculated for each electrocardiogram. T-wave
amplitudes were measured from the same baseline and added together in a like manner. The
summated ST-segment deviations and T-wave
amplitudes were used for comparing fasting electrocardiograms with those taken at successive 30minute intervals after glucose ingestion. Since
the changes in a given subject were in the same
direction in all leads, the sum of such changes
Ciirculation, Volume XXX, July 1964
Other coded items*
(No change during test)
for each electrocardiogram simplified comparisons; Simonson and McKinley employed a similar
method.6
Glucose was determined from whole blood by
an automated procedure with use of a modification of the Hoffman 12 technic.
Three subjects with coronary heart disease and
four without heart disease were re-examined with
saccharine in water instead of glucose.
Results
ST-segment and T-wave Changes after Oral Glucose Administration
Definite ST-segment shifts occurred in 28
of 30 subjects without heart disease, 24 showing depression and four elevation (table 2).
ST-segment shifts were observed in 21 of 23
subjects with coronary heart disease, 14
OSTRANDER, WEINSTEIN
70
showing depression and seven elevation. The
mean depression was greater for the 11 subjects receiving digitalis.
A decrease in T-wave amplitude followed
glucose ingestion in all 30 subjects without
heart disease. The greatest absolute changes
generally occurred in the subjects with the
highest fasting T-wave amplitudes. T-wave
amplitudes decreased after glucose ingestion
in 19 of 23 subjects with coronary heart disease, two did not change, and two showed
slight increases.
The seven subjects re-examined with sac-
charine in water showed only trivial differences between tracings. Blood glucose levels
changed little after the placebo.
Changes in Heart Rate after Glucose Administration
The subjects without heart disease had
a mean fasting heart rate of 70, while those
with coronary heart disease had a rate of 78.
Both groups showed a mean increase in rate
after glucose ingestion but the response was
variable resulting in a slower rate in some
subjects and increases up to 25 beats per
minute in a few (table 3).
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Figure 1
A "borderline" electrocardiogram recorded 90 minutes after the ingestion of 100 Gm.
of glucose shows diphasic T wvaves in chest leads V2-V coded V-3. This subject had
a normal fasting electrocardiogram and no evidence of heart disease.
4,
C(irculatiotz,
Volunte XXX, July 1964
ELECTROCARDIOGRAPHIC CHANGES AFTER GLUCOSE
71
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Figure 2
An abnormal electrocardiogram recorded 90 minutes after the ingestion of 100 Gm. of
glucose shows slight T-wave inversion in leads V3-V6, coded V-3. This subject had
angina pectoris but his fasting electrocardiogram was normal.
Men with the greater increases in heart
rate tended to have more marked ST-segment depression and a majority of the STsegment and T-wave changes coded by the
Minnesota system. There did not appear to
be any clear relation between absolute decreases in T-wave amplitude and increases in
heart rate (table 4).
pression in lead aVF, coded IV-3, and two
developed diphasic T waves in the midchest
leads after glucose ingestion, coded V-3 (table
5, fig. 1). When one of these subjects was
re-examined with use of a placebo, his electrocardiogram remained normal throughout
the test.
Subjects with Coronary Heart Disease
ST-segment and T-wave Changes Coded According to the Minnesota Criteria
Subjects without Heart Disease
One man developed slight ST-segment deCirculation, Volume XXX, July 1964
Most subjects with coronary heart disease had abnormal fasting electrocardiograms, and many tracings included coded
72
~~~~~~~~~~OSTRANDER,
WEINSTEIN
ST-segment and T-wave abnormalities prior to
glucose ingestion.
Eight subjects were re-coded after glucose
administration because of ST-segment or T
wave changes; five of these subjects were
receiving digitalis (table 5, fig. 2). Glucose
ingestion accentuated the ST-segment depression in most digitalized subjects, regardless of classification (fig. 3).
In general, postprandial ST-segment and
T-wave changes were less marked at the end
Blood Glucose Levels in Subjects with Coronary
Heart Disease and Those without Heart Disease
of the 2-hour test but some were still present.
The administration of oral glucose was fol-
Although subjects with known diabetes
excluded from the study, blood gluanalysis of th,e two groups revealed
higher mean blood glucose levels at each
time interval in the subjects with coronary
heart disease (table 6). The differences were
statistically significant at the 60-, 90-, and
.120-minute intervals after glucose.
were
cose
Discussion
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A.
T 77
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....
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.......
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:.
..
T-
.
::,.
-.::IN
7:
:..
Figure 3A
An abnormal electrocardiogramt from a fasting digitalized subject, showing AV nodal
rhythm and ST depression due to digitalis. This tracing was coded IV-I and VIIH-6.
Circulation, Volume XXX, July 1964
73
ELECTROCARDIOGRAPHIC CHANGES AFTER GLUCOSE
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3B
An electrocardiogram from the same subject as in figure 3A 30 minutes after the
ingestion of glucose shows more pronounced ST-segment depression and continued
AV nodal
rhythm. The code
was
unchanged.
lowed
curring
T-wave
wave
by changes in ST-segment elevations,
amplitudes, and heart rates in all
subjects. Slight depression of ST segments
occurred in most subjects who were not taking digitalis, while the ST-segment depression
in
resulting
the
postprandial
group
from
digitalis
digitalized subjects.
were
ST-segment
slight,
was
accentuated
While the
changes
oped clinically important changes
cose
for
few individuals
a
mean
each
devel-
after
glu-
amplitudes
decreased in most sub-
jects, the greatest quantitative
Cifrculation,
those
Volume XXX, July
1964
changes
oc-
with
the
most
T-
positive
fasting electrocardio-
gram.
The
after
mean
glucose
sponses
were
heart
in
rates
both
slightly
although re-
increased
groups,
quite variable. The degree of
ST-segment depression roughly paralleled
increases
crease
in heart rate, but
in T-wave
change
uted to gastric
not
amplitudes
the
the absolute dewas
unrelated
to
in heart rate.
The various
ingestion.
T-wave
in
deflections in the
reproduce
changes
filling,
them
could not be
in
the
attrib-
placebo did
seven
subjects
since the
74
OSTRANDER, WEINSTEIN
Table 6
Mean Blood Glucose Levels, Fasting and during Test
Fasting
Subjects without
apparent heart disease
Subjects with
coronary heart
disease
t test values
Number
Mean blood sugar mg. %
Number
Mean blood sugar mg. %
30
30
min.
28
132.9
23
139.7
89.3
23
93.6
1.24
1.90
60 min.
30
mmin.
30
90
132.0
117.8
23
156.3
146.9
23
120 min.
30
106.0
22
134.1
2.4*
* Significant at 0.05 level.
**
Significant at 0.01 level.
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who were retested. Potassium depletion may
explain the decrease in T-wave amplitudes
and the accentuation of digitalis effect on
the ST segments,10 but some of the changes
were not typical of hypokalemia. The terminal T-wave inversion observed in several
subjects suggested some other nonspecific
change in the myocardium.
When ST-segment and T-wave changes
in each electrocardiogram were classified according to the "Minnesota Code," three of 30
subjects without heart disease developed
postprandial changes, consisting of diphasic
T waves in two and slight ST-segment depression in the third.
Eight of the 23 subjects with coronary
heart disease developed new or more marked
ST-segment or T-wave changes after glucose
ingestion, although only one had a normal
fasting electrocardiogram. Five subjects were
receiving digitalis and in two the principal
change was deepening of the digitalis induced ST-segment depression.
Since oral glucose administration produced at least borderline ST-segment or Twvave changes in 10 per cent of the apparently normal subjects and failed to cause or
accentuate such changes in 65 per cent of
subjects with manifest coronary heart disease,
electrocardiograms after glucose are not likely to be a useful method for the detection of
occult coronary heart disease. Previous reports advocating such tests have not presented results in quantitative terms nor have
the interpretations of the electrocardiograms
been based on clearly defined criteria.
On the other hand, the quantitative STsegment and T-wave changes that generally
follow glucose ingestion may be of clinical
importance in the electrocardiograms of at
least a few subjects without other signs of
heart disease.
Because of the uncertain significance of
such changes, any ST-segment or T-wave abnormalities occurring after glucose ingestion
must be interpreted cautiously. Although
such changes may suggest underlying heart
disease, a diagnosis should not be based on
this evidence alone. Preferably glucose
should not be administered for several hours
before recording routine clinical electrocardiograms.
The higher mean blood glucose levels in
the coronary heart disease subjects may be
interpreted in several ways. Chronic hepatic
congestion can alter liver function sufficiently
to reduce glucose tolerance, but none of the
subjects studied was in definite congestive
heart failure at the time of the test. Aging is
also said to reduce glucose tolerance 13-1 7 and
the subjects with coronary heart disease had
a mean age 15 years older than the subjects
without heart disease. Several reports 18-23 in
have suggested that abnormalmetabolism are frequent in
atherosclerotic individuals. Although the effects of age and possible hepatic impairment
cannot be ignored,. there inay well be significant differences in glucose metabolism between subjects with coronary heart disease
and those without heart disease.
recent
ities in
years
glucose
CJi(u,tE/ilog),z, Volii-^ne XXX,X july I1964
ELECTROCARDIOGRAPHIC CHANGES AFTER GLUCOSE
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Summary
In order to determine the effect of glucose
ingestion on the electrocardiogram, 23 men
with coronary heart disease and 30 without
known heart disease had electrocardiograms
in the fasting state and serial tracings at 30minute intervals after the administration of
100 Gm. of oral glucose. In both groups the
mean changes after glucose ingestion were
slight ST-segment depression, a moderate
decrease in T-wave amplitude, and a slight
increase in heart rate, although individual
variability was great. When the electrocardiograms were classified by a uniform coding
system, new ST-segment or T-wave classifications were recorded for eight of 23 subjects
with coronary heart disease and three of 30
men without known heart disease.
Since ST-segment and T-wave changes
regularly follow glucose ingestion and are
sometimes of sufficient degree to suggest
heart disease in apparently normal individuals, electrocardiograms recorded within
several hours after glucose administration
must be interpreted with caution. Because of
the uncertain significance of postprandial STsegment and T-wave changes, electrocardiograms after glucose ingestion do not appear
to be a very useful method for the detection
of occult heart disease. Glucose ingestion
should be avoided before routine clinical
tracings.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
Acknowledgment
The authors thank Drs. Henry K. Schoch, Walter
Block, and Marcus Kjelsberg, for their valuable technical assistance, and are particularly grateful to Drs.
Frederick H. Epstein and Park W. Willis III for
their many helpful suggestions and criticisms.
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Fabricius and Discovery of Valves in Veins
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"April 10, 1565. Owing to the vacancy of the chair of surgery in our University
of Padua, created by the death of the eminent Fallopia, and since such a chair
is very useful and necessary for certain sciences, we have agreed to appoint the
appropriate individual in the person of the excellent Hyeronimo Fabrizio de
Acquapendente, who has a good grasp of the aptitude for science and particularly in view of his recent successes in the field of anatomy. And the said excellent Messer Hyeronimo, in addition to his lectures upon surgery, will also
undertake the necessary dissections during the four years of his appointment,
for which work we offer him a salary of 100 florins per annum with the agreement of the Signoria.' ". .
It was towards the end of the 1570's that he began to note peculiar formations
on the veins while dissecting: In places small flaps hung down into the inside
of the veins. They were like small sacks (usually two opposite one another)
and they resembled the valves of the heart. He was very pleased, not remembering ever having read about them. . .
Finally in 1601 (he was now 63 years old) he decided to publish a small book
about them, for he felt he had arrived at the solution of the problem.
The little sacks stood out into the inside of the veins with their openings
uppermost. They obstructed the downward flow of blood, for when they were
swollen the blood could proceed no further. What was the purpose of this
arrangement? It could only be that as the blood coursed towards the feet and
the lower extremities as well as towards the fingers, it would burst open the
walls of the veins with its weight if the small sacks did not prevent this from
happening. Filled with blood, the free ends of the two sacks lying opposite one
another fit together and prevented the further progress of the blood.
He made exact drawings of opened veins and pointed out that when the arm
is bound these valves become visible even from the outside in the form of
small protuberances.
Fabricius showed the pictures to his students, among them an Englishman
named Harvey who attentively examined the diagrams and listened to what
his teacher had to say.-TIBoR DOBY, M.D. Discoverers of Blood Circulation.
From Aristotle to the Times of Da Vinci and Harvey. New York, AbelardSchuman, 1963, p. 182.
.
Ciration, Volume XXX, July 1964
Electrocardiographic Changes after Glucose Ingestion
LEON D. OSTRANDER, JR. and BELSON JACK WEINSTEIN
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Circulation. 1964;30:67-76
doi: 10.1161/01.CIR.30.1.67
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