International Journal of Obesity (1999) 23, 211±216
ß 1999 Stockton Press All rights reserved 0307±0565/99 $12.00
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Gallstone disease risk in relation to body mass
index and waist-to-hip ratio in Japanese men
H Kodama1*, S Kono1, I Todoroki2, S Honjo2, Y Sakurai2, K Wakabayashi2, M Nishiwaki3, H Hamada3,
H Nishikawa4, H Koga4, S Ogawa5 and K Nakagawa6
1
Department of Public Health, Faculty of Medicine, Kyushu University, Fukuoka; 2Department of Public Health, National Defense
Medical College, Tokorozawa; 3Self-Defense Forces Fukuoka Hospital, Kasuga; 4Self-Defense Forces Kumamoto Hospital, Kumamoto;
5
Self-Defense Forces Sapporo Hospital, Sapporo and 6Self-Defense Forces Central Hospital, Tokyo, Japan
OBJECTIVE: To examine the relation of body mass index (BMI) and waist-to-hip ratio (WHR) to gallstones and
postcholecystectomy risk in middle-aged Japanese men.
DESIGN: Cross-sectional study.
SUBJECTS: We used 174 men with prevalent gallstones, 104 with postcholecystectomy and 6909 with normal
gallbladder in the consecutive series of 7637 men aged 48 ± 59 y receiving a preretirement health examination at four
hospitals of the Japan Self-Defense Forces between 1986 and 1994.
MEASUREMENTS: Gallbladder status was assessed by abdominal ultrasonography after an overnight fast. BMI was
calculated as weight in kilogram divided by height in square meters, and WHR was used as a measure of central
obesity. Analysis of the WHR was limited to a subset of data for the period 1991 ± 1994 (gallstones 113, postcholecystectomy 66 and normal gallbladder 4410).
RESULTS: After adjustment for hospital, rank in the Self-Defense Forces, cigarette smoking, alcohol use and glucose
tolerance, BMI was signi®cantly associated with an increased risk of both prevalent gallstones and postcholecystectomy. WHR also showed a signi®cant positive association with each of the two conditions. When BMI and WHR
were mutually adjusted for, both of the obesity indices tended to be associated positively with prevalent gallstones
and postcholecystectomy.
CONCLUSION: These ®ndings indicate that obesity is associated with increased gallstone risk in men.
Keywords: body mass index; gallstone disease; Japanese men; waist-to-hip ratio
Introduction
The importance of obesity as a risk factor for gallstone
disease has been well documented in women in
different populations studied by different methods.1 ± 10 However, the association with obesity as
measured by body mass index (BMI) or relative
weight is inconsistent in men.4 ± 12 Several studies
that found a positive relation between BMI and
gallstone disease in women failed to demonstrate
such an association in men.7 ± 10 Because gallstone
disease is far less prevalent in men than in women, the
statistical power may have been inadequate in these
studies. It has also been speculated that men may be
less liable to gallstone formation associated with
obesity.13
Interestingly, Heaton et al 11 recently observed in a
cross-sectional study of British men that waist-to-hip
ratio (WHR) was positively related to gallstone disease, whereas BMI was unrelated to the risk. In two
successive studies of men in the Japan Self-Defense
*Correspondence: H Kodama, Department of Public Health,
Faculty of Medicine, Kyushu University, Fukuoka 812-8582,
Japan.
Received 16 April 1998; revised 13 August 1998; revised
1 September 1998
Forces,14,15 BMI showed no more than a tendency of a
positive association with prevalent gallstones, and a
consistent positive association with postcholecystectomy. WHR was available in the latter study15 and a
less strong relation was observed between WHR and
gallstone disease. The present study pooled data used
in the previous studies14,15 and combined these with
data obtained subsequently, in order to examine more
precisely the relation of BMI and WHR to both
prevalent gallstones and postcholecystectomy determined by ultrasonography.
Methods
Subjects
The subjects were male self-defense of®cials who
received a preretirement health examination at the
Self-Defense Forces Fukuoka Hospital from October
1986 ± December 1994, at Kumamoto Hospital from
January 1991 ± December 1994, at Sapporo Hospital
from April 1992 ± December 1994 and at Central
Hospital from January 1993 ± December 1994. The
health examination is part of a nationwide program for
those retiring from the Self-Defense Forces. A total of
7637 men aged 48 ± 59 y were admitted to the four
Gallstone risk in Japanese men
H Kodama et al
212
hospitals (Fukuoka 4530, Kumamoto 838, Sapporo
1355 and Central 914). A total of 2656 men in the
period between 1993 and 1994 were newly added to
the present study.
Health examination
The health examination was undertaken during a ®veday admission and included abdominal ultrasonography, a 75 g oral glucose tolerance test (OGTT),
sigmoidscopy or colonoscopy, measurements of blood
biochemical indices and blood pressure, and others.
After subjects had fasted overnight, ultrasonography
of the gallbladder was performed by technicians using
an instrument with a 3.5- or 3.75-MHz transducer
(Aloka Co., Ltd, Mitaka, and Toshiba Co., Ltd,
Tokyo, Japan). Gallstones were diagnosed as mobile
echoes in the gallbladder lumen, usually accompanied
by an acoustic shadow. Based on the ultrasonography
report, the gallbladder status was classi®ed as follows:
gallstones, removed gallbladder, polyps, other disease
conditions, normal gallbladder and unsatisfactory
study.
Height and weight were recorded, and BMI, as a
measure of overall obesity, was calculated as
weight(kg)=height(m)2. The measurement of waist
and hip girth was included from 1991. Waist and
hip girth were measured to the nearest centimeter,
over single-thickness clothing, with the participant
standing in an erect position with feet together.
Waist circumference was measured at the umbilical
point and hip circumference was measured at the
largest circumference around the buttocks. WHR
was used as a measure of central obesity.
A 75 g OGTT was undertaken, after subjects had
fasted overnight. Subjects were classi®ed as normal,
impaired or diabetic with respect to glucose tolerance
according to World Health Organization (WHO) criteria.16 Men under dietary or drug treatment for
diabetes mellitus were regarded as diabetics. There
were 18 men whose glucose tolerance was not determined and who were not receiving treatment. They
were regarded as having normal glucose tolerance.
Lifestyle questionnaire
Smoking habit, alcohol use and other lifestyle characteristics were ascertained using a self-administered
questionnaire. The questionnaire was revised several
times in the course of the study period. However,
questions on smoking habit and alcohol use were
essentially the same throughout the study period.
Questions on physical activity were changed materially, and thus the variable was not suitable for the
present combined analysis.
Statistical analysis
Men with a normal gallbladder were used as controls
in the analysis. Odds ratios (ORs) of each of prevalent
gallstones and postcholecystectomy according to the
levels of the BMI and WHR were used to assess the
association with these obesity indices. BMI and WHR
were each categorized into four levels at the cutoff
points of the 30th, 60th and 90th percentiles in men
with a normal gallbladder. These cutoff points were
used because the study subjects were generally thin.
Furthermore, because BMI 25.0 has generally been
de®ned as overweight,17 the ORs were also calculated
for the categories of 22.5 ± 24.9 and 25.0 with
< 22.5 as the reference category. Statistical adjustments were made for hospital, rank in the SelfDefense Forces, cigarette smoking, alcohol use,
impaired glucose tolerance and diabetes mellitus,
using multiple logistic regression analysis.
Rank in the Self-Defense Force was categorized
into low, middle and high ranks. As regards cigarette
smoking, subjects were classi®ed into never smokers,
former smokers, and current smokers consuming < 25
or 25 cigarettes per day. As for alcohol use, subjects
were grouped into never drinkers, former drinkers and
current drinkers consuming < 30 ml, 30 ± 59 ml or
60 ml alcohol per day. Age was distributed in a
limited range from 48 ± 59 y, and the majority were
aged in their early 50s. Age was thus not taken into
account.
Indicator variables were created for categories
of BMI, WHR and the confounding variables. ORs
and 95% con®dence intervals (CI) were obtained
from logistic regression coef®cients and standard
errors for the corresponding indicator variables.
Two-side P-values < 0.05 were regarded as statistically signi®cant, and all statistical computations were
performed by using the Statistical Analysis System
(SAS).18
Results
In the consecutive series of 7637 men, 7598 underwent satisfactory ultrasonography of the gallbladder.
The numbers of men by gallbladder status were as
follows: gallstones 174, removed gallbladder 104,
polyps 390, other diseases 24, and normal gallbladder
6906. The overall prevalence rate of gallstone disease,
which combined gallstones and postcholecystectomy,
was 3.7% (278=7598).
Means (or s.e.) of BMI for normal gallbladder,
prevalent gallstones and postcholecystectomy were
23.78 (0.03), 24.17 (0.18), and 24.67 (0.27), respectively; as compared with the normal gallbladder
group, P-values based on t-test were 0.03 for prevalent gallstones and 0.0012 for postcholecystectomy.
The means (s.e.m.) of WHR were: normal gallbladder
0.901 (0.0007), prevalent gallstones 0.912 (0.004),
and postcholecystectomy 0.917 (0.006); P-values as
compared with the normal gallbladder group were
0.02 for prevalent gallstones and 0.016 for postcholecystectomy, respectively. Although the distributions
Gallstone risk in Japanese men
H Kodama et al
213
Table 1 Cigarette smoking, alcohol use, glucose intolerance and high rank, according to body mass index (BMI) in men with normal
gallbladder
Body mass indexa
Risk factor
Current smoking (%)
Cigarettes per day (mean)
Alcohol use (%)c
Alcohol (ml) per day (mean)
Glucose intolerance (%)d
High ranks (%)
< 22.42
22.42 ^ 24.32
24.33 ^ 27.04
27.05
Overall
differenceb
57.6
13.0
79.7
35.3
14.7
14.5
49.3
11.2
80.6
36.9
18.5
19.3
44.2
10.2
80.4
37.5
25.4
19.4
42.0
10.0
80.1
40.3
36.1
16.4
P < 0.0001
P ˆ 0.0001
P ˆ 0.89
P ˆ 0.01
P < 0.0001
P < 0.0001
a
Cutoff points were the 30th, 60th and 90th percentiles in men with normal gallbladder.
Chi-square test or Kruskal-Wallis test.
c
At least once per week.
d
Impaired glucose tolerance and diabetes mellitus combined.
b
Table 2
Crude and adjusted odds ratios (OR) and 95%
con®dence intervals (CI) of prevalent gallstones and
postcholecystectomy according to body mass index (BMI),
October 1986 ± December 1994
BMI (kg/m2)a
Prevalent gallstones
< 22.42
22.42 ± 24.32
24.33 ± 27.04
27.05
Postcholecystectomy
< 22.42
22.42 ± 24.32
24.33 ± 27.04
27.05
Cases (n)b
Crude OR
(95% CI)
Adjusted OR
(95% CI)c
33
62
59
20
1.0
1.9 (1.2 ± 2.9)
1.8 (1.2 ± 2.8)
1.8 (1.0 ± 3.2)
1.0
1.8 (1.2 ± 2.8)
1.8 (1.1 ± 2.8)
1.8 (1.0 ± 3.2)
22
20
45
17
1.0
0.9 (0.5 ± 1.7)
2.1 (1.2 ± 3.4)
2.3 (1.2 ± 4.4)
1.0
0.9 (0.5 ± 1.7)
2.1 (1.2 ± 3.5)
2.2 (1.2 ± 4.3)
a
Cutoff points were the 30th, 60th and 90th percentiles in men
with normal gallbladder.
b
Number of men with normal gallbladder from the lowest to
highest categories were 2070, 2082, 2064 and 690.
c
Adjusted for hospital, rank, cigarette smoking, alcohol use and
glucose tolerance by multiple logistic regression analysis.
of BMI and WHR were slightly skewed to the higher
values, means and standard errors were used for ease
of presentation because signi®cance tests using a nonparametric method resulted in almost the same results.
Distributions of the possible confounding variables
according to BMI are summarized in Table 1. Current
smoking was less frequent among men with a higher
BMI and the number of cigarettes smoked per day was
less in more obese men. While the proportions of
alcohol drinkers, de®ned as those drinking at least
once per week, did not vary with BMI levels, the
average amount of alcohol consumed per day tended
to be greater with increasing levels of BMI. There was
a strong, positive association between BMI and glucose intolerance. Men of high ranks tended to be
among those at the highest 70% of BMI, but the
proportions were not progressively higher with
increasing levels of BMI.
Table 2 shows crude and adjusted ORs of prevalent
gallstones and postcholecystectomy according to
BMI. Little difference was noted between crude and
adjusted ORs of prevalent gallstones or postcholecys-
tectomy. ORs of prevalent gallstones and postcholecystectomy were not progressively increased with
BMI levels; approximately two-fold, signi®cant
increases in the ORs were observed for the highest
three levels of BMI as regards prevalent gallstones
and for the highest two levels as to postcholecystectomy. Adjusted ORs (and 95% CI) of prevalent gallstones for the categories of BMI of < 22.5, 22.5 ± 24.9
and 25.0 were 1.0 (reference), 2.0 (1.3 ± 3.0) and 1.6
(1.0 ± 2.5), respectively. The corresponding values for
postcholecystectomy were 1.0 (reference), 1.2 (0.7 ±
2.0), and 2.1 (1.3 ± 3.6), respectively.
In order to evaluate whether WHR was more
strongly associated with gallstone disease than BMI
and whether any association between WHR and gallstone disease was independent of BMI, we analyzed a
subset of data in which the WHRs were available
(Table 3). After adjustment for hospital, rank, cigarette smoking, alcohol use and glucose tolerance,
prevalent gallstones and postcholecystectomy
showed positive relationships with WHR, and the
ORs for the highest category were signi®cantly different from unity. When additional adjustment was
made for BMI, ORs of prevalent gallstones and
postcholecystectomy showed a moderate, statistically
nonsigni®cant increase among men at the highest
level of WHR. Adjusted ORs (and 95% CI) of prevalent gallstones for the lowest to highest levels of
BMI, derived from the multiple logistic regression
model including WHR used in Table 3, were 1.0
(reference), 1.5 (0.9 ± 2.7), 1.6 (0.9 ± 2.9) and 1.3
(0.6 ± 2.8). The corresponding ®gures for postcholecystectomy were 1.0 (reference), 0.9 (0.4 ± 1.9), 1.4
(0.6 ± 3.0) and 1.9 (0.8 ± 4.7).
Discussion
Pooling the data used previously14,15 and unpublished
data accrued subsequently, the present study demonstrated that BMI and WHR were associated positively
Gallstone risk in Japanese men
H Kodama et al
214
Table 3
Adjusted odds ratios (OR) and 95% con®dence intervals (CI) of prevalent gallstones and
postcholecystectomy according to waist-to-hip ratio (WHR), January 1991 ± December 1994
Adjusted OR (95% CI)c
WHRa
Prevalent gallstones
< 0.879
0.879 ± 0.912
0.913 ± 0.958
0.959
Postcholecystectomy
< 0.879
0.879 ± 0.912
0.913 ± 0.958
0.959
Cases (n)b
Without adjustment for BMI
With adjustment for BMI
28
27
41
17
1.0
1.0 (0.6 ± 1.7)
1.5 (0.9 ± 2.5)
1.9 (1.0 ± 3.6)
1.0
0.9 (0.5 ± 1.5)
1.3 (0.7 ± 2.3)
1.7 (0.8 ± 3.4)
14
18
22
12
1.0
1.4 (0.7 ± 2.8)
1.8 (0.9 ± 3.6)
3.0 (1.4 ± 6.7)
1.0
1.2 (0.6 ± 2.6)
1.4 (0.7 ± 3.1)
2.1 (0.8 ± 5.3)
BMI ˆ body mass index.
Cutoff points were the 30th, 60th and 90th percentiles in men with normal gallbladder.
b
Number of men with normal gallbladder from the lowest to highest categories were 1343, 1318, 1310 and
439.
c
Adjusted for hospital, rank, cigarette smoking, alcohol use and glucose tolerance, without and with
additional adjustment for BMI as categorized in Table 2.
a
with both prevalent gallstones and postcholecystectomy. When these two obesity indices were mutually
adjusted for, the associations were attenuated; yet both
of them tended to be related to an increased risk. BMI
and WHR were highly correlated with each other
(Pearson correlation coef®cient 0.56). Statistical
adjustment for such a co-linear variable may cause
dif®culties in interpretation. Nonetheless our ®ndings
add to evidence that obesity increases gallstone risk in
men as well.
Previous studies have reported inconsistent associations of BMI or relative weight with gallstone disease
in male populations. In a case-control study in Australia,7 there was virtually no difference in BMI
between gallstones cases and either hospital or community controls in men, while there was a positive
association between BMI and gallstones in women.
Another case-control study in The Netherlands
showed a positive association in both men and
women.6 Two prospective studies found a positive
association for relative weight or BMI with clinical
gallstone disease in men and women separately in
Framingham, USA4 and in Japanese men in Hawaii.12
Cross-sectional analyses in the San Antonio Heart
Study consistently show a clear, positive association
between BMI and self-reported gallstone disease in
men as well as in women.5,19 Three population screening surveys using ultrasonography failed to ®nd a
positive association for BMI with prevalent gallstones
or gallstone disease (prevalent gallstones and postcholecystectomy combined) in men in Italy,8 Denmark9 and the USA,10 while all three showed a
positive association in women. A similar population
study of British men also failed to show a positive
association between BMI and gallstone disease.11
The inconsistency in men as regards BMI and
gallstone disease has not been fully explained. BMI
may not be a suitable measure of obesity in men.
Heaton et al 11 showed a progressive increase in the
risk of gallstone disease with increasing levels of
WHR, but not of BMI, in men. However, neither
WHR nor subscapular-to-triceps skinfold was related
to gallstone disease risk in men in the San Antonio
Heart Study, while these indices of central obesity
were associated with increased risk in women.5,19 Our
®ndings indicate that WHR is not more strongly
associated with either prevalent gallstones or postcholecystectomy than BMI.
Obesity is associated with increased saturation of
bile with cholesterol in both men and women.20,21
Hyperinsulinaemia, associated with obesity, may be
responsible for the cholesterol saturation in bile.
Insulin increases the activity of HMG-CoA reductase,
the rate-limiting enzyme for cholesterol synthesis in
the liver.22,23 Insulin also activates low-density lipoprotein (LDL) receptors in the liver, and thereby
increasing cholesterol excretion in the bile.24 In fact,
hyperinsulinaemia has been shown to be associated
with increased risk of gallstones in several studies.7,11,19
Several limitations in the present study should be
discussed. We did not ascertain BMI or WHR in the
past. The current levels of obesity may not be relevant
to prevalent gallstones, and especially to postcholecystectomy. It is possible that the observed positive
association between obesity and postcholecystectomy
may have been due to weight gain after cholecystectomy.25,26 Caution is thus needed in interpreting the
®ndings regarding postcholecystectomy. Although
rapid weight reduction is known to enhance gallstone
formation,27,28 much of the risk associated with
weight loss or dieting has been ascribed to the underlying obesity or excess weight before dieting.3,6,9 The
type of gallstones was not determined, but the majority of gallstones in the present study are probably
cholesterol stones.29 Men serving for the Self-Defense
Gallstone risk in Japanese men
H Kodama et al
Forces until retirement are not representative of those
of the general population and our ®ndings may not be
generalized. However, the mean BMI of the study
subjects was comparable to that of the average
middle-aged Japanese man; BMI for men aged 50 ±
59 y was estimated to be 23.3 from the average height
and body weight reported in the National Nutrition
Survey in 1990.30 The prevalence of gallstone disease,
prevalent gallstones and postcholecystectomy combined, was similar to that reported elsewhere in
Japan;31 the prevalence was 2.7% for men aged in
their 50s in that study. However, these Japanese
®gures were much lower than those reported for
men aged 50s or early 50s in Western populations;
the prevalence rates for gallstone disease were 6.7%
in Denmark,32 24.5% in Norway,33 7.5% in Britain34
and 10.0% in Italy.35
In summary, based on a large number of middleaged men screened by gallbladder ultrasonography,
the present study showed a positive association for
BMI and WHR each with prevalent gallstones and
postcholecystectomy, and indicate that obesity
enhances gallstone formation in men as well.
Acknowledgements
This study was supported in part by the Grant-in-Aid
for Cancer Research (2-3 and 4-2) from the Ministry
of Health and Welfare, Japan. The authors are grateful
to the ward nurses of the Self-Defense Forces
Fukuoka, Kumamoto, Sapporo and Central Hospitals
for their cooperation and to Ms Satoko Kiyono and
Mami Mochida for their assistance.
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