Insulin resistance syndrome as a feature of cardiological syndrome X in non-obese men
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Downloaded from http://heart.bmj.com/ on October 11, 2015 - Published by group.bmj.com
Br Heart3' 1994;71:41-44 41
Insulin resistance syndrome as a feature of
cardiological syndrome X in non-obese men
Jonathan W Swan, Christopher Walton, Ian F Godsland, David Crook, Michael F Oliver,
John C Stevenson
Abstract abnormalities within the blood or myo-
Objective-To assess the features of the cardium resulting in ischaemia,' and reduced
insulin resistance syndrome in patients blood flow secondary to either microvascular
presenting with cardiological syndrome disease45 or alterations in vasomotor tone.6
X, who experience angina despite angio- Recently, the combination of insulin resis-
graphically normal coronary arteries. tance, hyperinsulinaemia, high plasma triglyc-
Patients and methods-14 Non-obese eride concentration, low high density
male patients with syndrome X and 38 lipoprotein (HDL) cholesterol concentration,
symptom free, apparently healthy, male and raised blood pressure has also, confus-
volunteers were studied. Insulin sensi- ingly, been labelled syndrome X.7 Insulin
tivity (inversely related to insulin resis- resistance seems to underlie these related
tance) was measured by minimal disturbances in risk factors for coronary
modelling analysis of glucose and insulin heart disease and the term insulin resistance
concentrations during an intravenous syndrome may be more appropriate.
glucose tolerance test. Serum lipids, As hyperinsulinaemia has also been impli-
lipoproteins, and apolipoproteins were cated in the pathogenesis of cardiological syn-
also measured. drome X,8 we investigated a group of patients
Results-Insulin sensitivity was 31% with syndrome X angina to see if they had the
lower in the men with syndrome X insulin resistance syndrome.
(p < 0.05) and fasting insulin concentra-
tion was 30% higher (p < 0.05). The
patient group also had 64% higher mean Patients and methods
triglycerides (p < 0.001) and 20% lower PATIENTS
mean high density lipoprotein choles- Fourteen non-obese, white, male patients of
terol concentration (p < 0.01). Systolic mean age 46-6 (range 31-59) years were
blood pressure was also 10% higher in selected after review of cardiac catheterisation
the syndrome X group (p < 0.01). There and case records. All patients reported a his-
were no differences in total cholesterol, tory of chest pain typical of angina pectoris,
low density lipoprotein cholesterol or with electrocardiographic evidence of
lipoprotein (a). ischaemia on exercise but normal coronary
Conclusion-These findings show that arteries at angiography. Coronary arteri-
non-obese male patients with anginal ograms were considered normal if there were
chest pain but normal coronary arteries no stenoses on visual inspection by two expe-
(syndrome X) are insulin resistant, rienced observers. An exercise test was per-
hyperinsulinaemic, and have higher con- formed to the Bruce protocol and considered
centrations of triglycerides and lower positive for ischaemia if ST segment depres-
high density lipoprotein cholesterol than sion > 1 mm developed in any leads at peak
healthy men. The insulin resistance syn- exercise. Patients were excluded if they had
drome may predispose to a spectrum of taken any drugs known to affect lipid or
arterial disease capable of causing carbohydrate metabolism in the previous 6
myocardial ischaemia. months, if there was any evidence of struc-
tural heart disease, or if they deviated by
(Br Heart _j 1994;71:41-44) more than 20% from their ideal body weight
(Metropolitan Life tables9).
Cardiologists use the term syndrome X to CONTROLS
Wynn Institute for refer to patients who present with anginal Thirty eight apparently healthy and clinically
Metabolic Research,
London chest pain, are found to have a positive exer- normal, male, white, volunteers of mean age
J W Swan cise electrocardiogram suggestive of myocar- 47-3 (range 30-60) years were also studied.
C Walton dial ischaemia, but no angiographic evidence They were seen as part of a medical health
I F Godsland
D Crook of atherosclerotic coronary artery disease.' screening programme and none had any
M F Oliver The pathological mechanisms responsible for symptoms suggestive of heart disease.
J C Stevenson
the chest pain in this condition, which was Physical examination and resting electrocar-
Correspondence
Dr J W Swan, Wynn
to:
originally described by Kemp,2 remain diogram were normal in each case. They were
Institute for Metabolic obscure. In the absence of stenoses of a also selected to be within 20% of their ideal
Research, 21 Wellington
Road, London NW8 9SQ.
coronary artery, various theories have been body weight and were taking no medication
proposed to explain the origin of the known to affect lipid or carbohydrate metab-
Accepted for publication
23 August 1993. symptoms. These include biochemical olism.Downloaded from http://heart.bmj.com/ on October 11, 2015 - Published by group.bmj.com
42 Swan, Walton, Godsland, Crook, Stevenson
Table 1 Population characteristics then the HDL, subfraction was measured
Syndrome X Controls after further precipitation with dextran
Age (yr) 46-6 (2 4) 47-3 (1-5)
sulphate.12 The HDL, subfraction was
Height (m) 179 (2.5) 176 (1-2) calculated as the difference between HDL
Weight (kg) 80-0 (2.5) 76-4 (1-4) and HDL,. Low density lipoprotein (LDL)
Body mass index (kg/M2) 24-8 (0.6) 24-5 (0-3)
Systolic blood pressure (mm Hg) 130 (4-0) 118 (2 2) cholesterol was calculated from the
Diastolic blood pressure (mm Hg) 78 (3-0) 75 (1-5) Friedewald formula."3 Apolipoproteins AI and
Current smokers (%) 7 27
Previous smokers (%) 64 60 B were measured by immunoturbidimetry"4
Values are mean (SEM).
and lipoprotein (a) by an enzyme linked
immunosorbent assay (ELISA) method
(Biopool, Sweden).
Table 2 Lipids and lipoproteins
Syndrome X Controls p Value ANALYSIS DATA
Incremental glucose, insulin, and C-peptide
Total cholesterol (mmoIl/) 5-17 (0 26) 5-14 (0-13) NS areas (the area between the fasting concentra-
Triglyceride (mmoll)* 1-56 (+0 26,-0 23) 0-95 (+0-08,-0 07)Downloaded from http://heart.bmj.com/ on October 11, 2015 - Published by group.bmj.com
Insulin resistance syndrome as a feature of cardiological syndrome X in non-obese men 43
Figure 1 Mean plasma and raised blood pressure compared with
concentration profiles for healthy men. Earlier work has shown that
blood glucose, insulin, and
C-peptide before and after insulin resistance and hyperinsulinaemia are
a 05 glkg intravenous associated with increased plasma triglycerides
glucose load. 20 * Syndrome)
O Controls K]0
E and low plasma HDL cholesterol.'7 18
E
Similarly, a close relation between blood
0
en pressure and insulin resistance has been
10 described in both hypertensive and nor-
FDI motensive persons.'719 It has been suggested
i----ji that the insulin resistance syndrome may be
0
associated with the development of athero-
sclerosis and coronary heart disease.7
600
A recent study has also shown insulin resis-
tance, by the euglycaemic clamp method, in
11 patients with syndrome X compared with
nine controls with non-cardiac chest pain.20
o 400 By contrast with our findings, these authors
E
a failed to show significant differences in serum
cholesterol, triglycerides, HDL cholesterol, or
blood pressure. Mean serum HDL choles-
200
terol concentration was, however, 12% lower
and mean serum triglycerides 14% greater in
the syndrome X group, findings consistent
with the insulin resistance syndrome.
In our study we excluded those with hyper-
2 tension, diabetes, obesity, and other known
insulin resistant states.'9 21 22 Furthermore, the
groups were closely matched for body mass
E index and age, both of which have been
0 reported to affect sensitivity to insulin.23 24
E
-L 1
Smoking has been reported to increase
insulin resistance25 but cannot be responsible
C)
for our findings as there was a similar propor-
tion of previous smokers in each group, with
QL I more current smokers in the control group.
The difference in previous and current smok-
n I II Il .i.., .j
..., ing habits probably reflects clinical advice
30 60 90 120 150 180 given to patients with chest pain. The differ-
Time (min) ence found in insulin resistance is likely to
relate to the diagnosis of syndrome X.
Although our study could not find a causative
role for the insulin resistance syndrome in
of total cholesterol, LDL cholesterol, syndrome X, the similarity of metabolic
apolipoprotein B, or lipoprotein (ax) (table 2). profile between syndrome X and atheroscle-
Fasting plasma glucose coIncentrations rotic coronary heart disease suggests a com-
were similar in both groups despite a mon aetiology or common underlying
significantly higher fasting insulin concentra- pathology.
tion in the syndrome X group (p < 005, The insulin resistance found in these men
table 3). Figure 1 shows plasma concentra- with syndrome X was associated with both
tion profiles for glucose, insuliin, and C- fasting and stimulated hyperinsulinaemia
peptide during the IVGTT. A greater despite a normal fasting blood glucose con-
insulin response was seen in men with centration and normal glucose tolerance. We
syndrome X, but plasma gllucose and divided the hyperinsulinaemic response to
C-peptide responses were similai r. A greater glucose into first phase, representing mainly
second phase response was resrponsible for secretion of stored insulin, and second phase,
TP _
6- - pI- 2
lower in the syndrome X giroup (3 40
C (+O061,-0-56) v 4 95 (+040,-O 38) x 10-5 were no significant differences in either first
min-'/(pmol/l), p < 005, fig 2). or second phase C-peptide response suggest-
ing that increased pancreatic secretion alone
e+ 4o' does not account for the increased insulin
Discussion response in these patients and that altered
These men with cardiological s yndrome X insulin elimination may be contributory.
Figure 2 Insulin have all the characteristic featLares of the Myocardial ischaemia is thought to be a
sensitivity derivedfrom the insulin resistance syndrome: hLyperinsulin- feature of cardiological syndrome X and has
minimal model in men been shown by a number of alternative meth-
with syndrome X and aemia, increased triglyceride conicentrations,
controls. decreased HDL cholesterol conicentrations, ods as well as the exercise electrocardiogramDownloaded from http://heart.bmj.com/ on October 11, 2015 - Published by group.bmj.com
44 Swan, Walton, Godsland, Crook, Stevenson
used in our study. These have included angina ("syndrome X"). Lancet 1991;i:456-7.
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Henderson AH. Hyperinsulinaemia and microvascular Diabetologia 1981;20:155-8.Downloaded from http://heart.bmj.com/ on October 11, 2015 - Published by group.bmj.com
Insulin resistance syndrome as a feature of
cardiological syndrome X in non-obese men.
J. W. Swan, C. Walton, I. F. Godsland, D. Crook, M. F. Oliver and J. C.
Stevenson
Br Heart J 1994 71: 41-44
doi: 10.1136/hrt.71.1.41
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