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Comparative study of blood insulin levels in breast and endometrial
V.B. GAMAYUNOVA, YU. F. BOBROV, E. V. TSYRLINA, T. P. EVTUSHENKO, L. M. BERSTEIN*
Laboratory of Endocrinology, Prof. N.N. Petrov Research Institute of Oncology, 189 646 St.Petersburg, Russia
Blood insulin level was measured in 113 breast cancer (BC) patients, 18 endometrial cancer (EC) patients, and 35 women
with benign breast disease (BBD), after fasting and after 120 min of oral glucose tolerance test (OGTT). A significant
increase in reactive insulin level was shown in postmenopausal BC patients with abdominal obesity (waist/hip ratio > 0.85)
and no differences in insulin level were found between BC and BBD patients. Menstrual status and overweight (Quetelet
index) did not influence significantly blood insulin concentration in BC patients, but the basal insulin level was lower in
those patients who had been moderate smokers. In EC patients, the level of insulin after fasting and following 120 min
OGTT was much higher than in BC and BBD patients although they had a similar body mass to these groups of patients. The
effect of age on insulin secretion in BC patients is discussed as well as the possible causes and consequences of hyperin-
sulinemia developing in EC and BC patients.
Key words: Insulin, breast cancer, endometrial cancer, benign breast disease, aging, upper type of obesity, smoking.
Insulin may directly or indirectly promote somatic cell
early cancer of the endometrium or ovary but levels fell to
division, enhance the activity of lipoprotein lipase, increase
normal after surgery or in advanced disease .
body fat concentration, and take part in modification of cel-
In earlier studies [3, 4, 7, 8, 17] we have reported that hy-
lular immunity and metabolic immunodepression (for re-
perinsulinemia is a key element leading to hyperlipidemia,
view see [8, 11]). In a case-control study of 223 women,
obesity, and age-associated disturbances in tolerance to car-
BRUNING et al.  have concluded that hyperinsulinemia and
bohydrates and it was postulated that in breast and endome-
insulin resistance are risk markers for breast cancer and are
trial cancer patients, the changes in blood insulin and glucose
independent of general obesity and body fat distribution.
levels might promote stimulation of tumor growth, or modi-
These authors found increased C-peptide concentration in
fications in immune defence mechanisms. The present work
the serum of breast cancer patients (higher in postmeno-
reports the insulin response to the oral glucose tolerance test
pausal than premenopausal women) compared to that of
(OGTT) in patients with early breast cancer and relates it to
patients with other types of cancer (melanoma, cervical can-
menstrual status, body mass (Quetelet index), type of fat to-
cer, malignant lymphoma). DEL GIUDICE et al.  also report
pography and smoking. Patients with endometrial cancer or
hyperinsulinemia to be a risk factor for premenopausal breast
benign breast disease were investigated as control groups.
cancer development but details are not available. It has been
suggested that overrich diet and insufficient physical exer-
cise may favor the development of hyperinsulinemia and
increase the risk of breast cancer in women, especially in
those with genetic susceptibility to neoplastic development
113 patients with breast cancer, 18 patients with early
. Hyperinsulinemia has also been noted in women with
endometrial cancer, and 35 women with benign breast dis-
ease were investigated at our Institute between 1992 and
1995. None had received any therapy before the examina-
*Author to whom correspondence should be sent.
tion and their ages ranged from 25 to 77. Of 113 breast can-
GAMAYUNOVA, BOBROV, TSYRLINA, EVTUSHENKO, BERSTEIN
Table 1. Blood glucose and insulin levels (M ± m) in breast cancer (BC),
spectively. Also Quetelet index (weight, kg/height (m2)) was
endometrial cancer (EC) and benign breast disease (BBD) patients
calculated, and as a criterion of fat distribution, the waist/hip
ratio was measured. Differences between the studied groups
were evaluated by Students t-test. Besides mean values (M),
standard deviations (σ) and standard errors (m), linear corre-
lation coefficients (γ) were also calculated. The computer-
52.1 ± 0.5 69.7 ± 1.2 90.5 ± 1.6 111.7 ± 3.8
ized statistical analysis was used for estimation of the results.
BBD 50.0 ± 2.1 71.8 ± 2.5 94.6 ± 3.3 118.1 ± 6.4
60.1 ± 2.2 70.0 ± 3.5 100.5 ± 2.9b 134.9 ± 9.8a 14.3 ± 2.0b,c 67.1±10.9b,d
n = 18a Difference from BC group is significant (p < 0.05), b difference from
BC group is significant (p < 0.01), c difference from BBD group is signi-
Table 1 shows the results of blood glucose and insulin
ficant (p < 0.05), d difference from BBD group is significant (p < 0.01).
measurement in BC, EC and BBD patients after night fast-
ing, and 120 min following the oral glucose load. It is seen
from the table, that glucose and insulin levels in BC patients
cer (BC) patients (all of them at an early clinical stage), 57
are similar to those in BBD patients and their mean values of
patients aged from 25 to 52 were premenopausal, and 56
body weight and age are practically the same. Average values
patients aged from 47 to 77 were postmenopausal for more
of body weight in EC patients were similar to those in BC and
than 12 months. Among 18 patients with early endometrial
BBD patients. In EC patients, blood insulin concentrations
cancer (EC), 3 women were premenopausal and 15 women
sampled following night fasting and by the 120-min of OGTT
postmenopausal for at least a year. The third group consist-
were significantly higher than those in BC and BBD patients,
ed of 35 women with either diffuse or nodular benign breast
while their levels of basal and reactive glycemia exceeded
disease (BBD) and comprised 22 premenopausal and 13
postmenopausal women. The total number of cases was 166
When the data were analyzed according to whether the
and none had a history or evidence of overt diabetes melli-
patients were pre- or postmenopausal (Table 2), blood insulin
and glucose levels after night fasting and 2 h following the
Blood insulin and glucose levels were determined after
glucose load were found to be similar in pre- and postmeno-
night fasting and during oral glucose tolerance test - peroral
pausal BC patients. Mean values of body weight of these pa-
glucose load (40 g/m2 of body surface). Glucose concentra-
tients were also similar. Postmenopausal BBD patients showed
tion in serum sampled from the cubital vein was measured by
a significant rise in glycemia level after 120 min OGTT as
enzymo-colorimetrical method using special kits (Boehring-
compared to premenopausal BBD patients. Postmenopausal
er Mannheim Gmbh, FRG). Commercial RIA kits (Nonor-
BBD patients also demonstrated a tendency to a larger body
ganic Chemistry Institute, Minsk, Belarus) were used for in-
mass and an enhanced reactive insulin level. However, an in-
sulin determination. Intraassay coefficients of variation for
creased blood insulin concentration was most pronounced in
insulin and glucose concentrations were 5.0% and 4.3%, re-
postmenopausal EC patients although they did not differ sig-
Table 2. Blood glucose and insulin levels (M ± m) in pre- and postmenopausal BC, EC and BBD patients
a Difference from BBD group of reproductive age is significant (p < 0.02), b difference from BC group of reproductive and postmenopausal age is
significant (p < 0.02), c difference from BBD group of postmenopausal age is significant (p < 0.05).
COMPARATIVE STUDY OF BLOOD INSULIN LEVELS IN BREAST AND ENDOMETRIAL CANCER PATIENTS
Table 3. Blood glucose and insulin levels (M ± m) in BC patients with different Quetelet index values and different types of fat topography
a Difference from postmenopausal patients with Quetelet index <30 is significant (p < 0.05), b difference from postmenopausal patients with waist/hip
(W/H) ratio <0.85 is significant (p < 0.05).
nificantly in their body mass and glycemia level from the EC
Table 4. Coefficients of linear correlation between basal and reactive
patients of reproductive age (Table 2).
(120 min after glucose load) blood insulin level and some indices in
Table 3 shows that an increase of Quetelet index over 30
was not accompanied by a significant rise in blood insulin
concentration either in premenopausal or in postmenopausal
BC patients. However, postmenopausal BC patients with the
abdominal (or android) type of fat topography (waist/hip ra-
insulin insulin insulin insulin insulin insulin
tio > 0.85) demonstrated a pronounced hyperinsulinemia by
0 min 120 min 0 min 120 min 0 min 120 min
120 min OGTT as compared with patients with a waist/hip
Correlation analysis in breast and endometrial cancer pa-
tients (Table 4) shows that anthropometric parameters exert a
greater effect on insulin levels in EC patients than in BC pa-
tients. In postmenopausal BC patients, the correlation between
insulin level and age was stronger than that between insulin
Table 5. Blood glucose and insulin levels (M ± m) in pre- and postmeno-
pausal smoking and non-smoking BC patients
Among BC patients, 35 women (31.0%) were moderate
smokers (they smoked on the average 7 cigarettes per day).
When the relationship between the studied parameters and
smoking habits was analyzed (Table 5), blood insulin levels
non-smoking 90.0 ± 2.7 112.6 ±7.1 7.4 ± 0.9 38.9 ± 7.6
were found to be lowest in postmenopausal BC patients who
had smoked over 5 cigarettes a day, whereas glucose concen-
89.2 ± 3.5 100.5 ±5.7 8.9 ± 1.4 29.0 ± 3.5
trations were practically identical in all other groups.
88.2 ± 6.5 101.3 ±9.4 7.9 ± 2.7 32.8 ± 5.6
non-smoking 93.9 ± 2.5 116.5 ±6.6 7.9 ± 0.7 37.6 ± 3.9
82.2 ± 6.6 113.7 ±16.1 8.2 ± 1.6 32.3 ± 12.3
Our study shows that blood insulin levels in BC patients
are similar to those in BBD patients and are not affected by
84.1 ± 9.5 100.2 ± 24.9 5.8 ± 0.5* 23.0 ± 10.0
menstrual status or by overweight (Quetelet index). However,
only postmenopausal women with the abdominal obesity
Difference from non-smoking patients of the same group is significant
(waist/hip ratio > 0.85) show a higher level of hyperinsuline-
mia by 120 min of OGTT, than those with lower body type of
obesity (Tables 13). Many authors [3, 12, 16] have noted
that hyperinsulinemia and insulin resistance are associated
In our study we failed to observe any differences in blood
with abdominal obesity, a decreased blood level of sex hor-
insulin concentrations between patients with early stage
mone-binding globulin (SHBG) and corresponding increase
BC, and BBD cases of the same age group and the same
of free blood estradiol concentrations.
menstrual status (Table 2). The progression of hyperin-
GAMAYUNOVA, BOBROV, TSYRLINA, EVTUSHENKO, BERSTEIN
sulinemia and insulin resistance in BC patients with age
was noted in our earlier work [4, 8]. In this study, the age-
dependent character of insulinemia in BC patients is most
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