Duration of breast-feeding and the incidence of type 2 diabetes mellitus in the Shanghai Women's Health Study.

Abstract

The aim of this study was to examine the association between lifetime breast-feeding and the incidence of type 2 diabetes mellitus in a large population-based cohort study of middle-aged women.
This was a prospective study of 62,095 middle-aged parous women in Shanghai, China, who had no prior history of type 2 diabetes mellitus, cancer or cardiovascular disease at study recruitment. Breast-feeding history, dietary intake, physical activity and anthropometric measurements were assessed by in-person interviews. The Cox regression model was employed to evaluate the association between breast-feeding and the risk of type 2 diabetes mellitus.
After 4.6 years of follow-up, 1,561 women were diagnosed with type 2 diabetes mellitus. Women who had breastfed their children tended to have a lower risk of diabetes mellitus than those who had never breastfed [relative risk (RR)=0.88; 95% CI, 0.76-1.02; p=0.08]. Increasing duration of breast-feeding was associated with a reduced risk of type 2 diabetes mellitus. The fully adjusted RRs for lifetime breast-feeding duration were 1.00, 0.88, 0.89, 0.88, 0.75 and 0.68 (p trend=0.01) for 0, >0 to 0.99, >0.99 to 1.99, >1.99 to 2.99, >2.99 to 3.99 and >or=4 years in analyses adjusted for age, daily energy intake, BMI, WHR, smoking, alcohol intake, physical activity, occupation, income level, education level, number of live births and presence of hypertension at baseline.
Breast-feeding may protect parous women from developing type 2 diabetes mellitus later in life.

Full text

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ARTICLE
Duration of breast-feeding and the incidence
of type 2 diabetes mellitus in the Shanghai Women’s
Health Study
R. Villegas & Y.-T. Gao & G. Yang & H. L. Li & T. Elasy &
W. Zheng & X.-O. Shu
Received: 18 July 2007 /Accepted: 22 October 2007 / Published online: 27 November 2007
# Springer-Verlag 2007
Abstract
Aims/hypothesis The aim of this study was to examine the
association between lifetime breast-feeding and the inci-
dence of type 2 diabetes mellitus in a large population-
based cohort study of middle-aged women.
Methods This was a prospective study of 62,095 middle-
aged parous women in Shanghai, China, who had no prior
history of type 2 diabetes mellitus, cancer or cardiovascular
disease at study recruitment. Breast-feeding history, dietary
intake, physical activity and anthropometric measurements
were assessed by in-person interviews. The Cox regression
model was employed to evaluate the association between
breast-feeding and the risk of type 2 diabetes mellitus.
Results After 4.6 years of follow-up, 1,561 women were
diagnosed with type 2 diabetes mellitus. Women who had
breastfed their children tended to have a lower risk of diabetes
mellitus than those who had never breastfed [relative risk
(RR)=0.88;95% CI,0.76–1.02; p=0.08]. Increasing duration
of breast-feeding was associated with a reduced risk of type 2
diabetes mellitus. The fully adjusted RRs for lifetime breast-
feeding duration were 1.00, 0.88, 0.89, 0.88, 0.75 and 0.68
(p trend=0.01) for 0, >0 to 0.99, >0.99 to 1.99, >1.99 to 2.99,
>2.99 to 3.99 and ≥4 years in analyses adjusted for age, daily
energy intake, BMI, WHR, smoking, alcohol intake, physical
activity, occupation, income level, education level, number
of live births and presence of hypertension at baseline.
Conclusions/interpretation Breast-feeding may protect par-
ous women from developing type 2 diabetes mellitus later
in life.
Keywords Lifelongbreast-feeding.Middle-agedwomen.
Parouswomen.Type2diabetesmellitus
Abbreviations
MET
RR
SWHS
metabolic equivalents
relative risk
Shanghai Women’s Health Study
Introduction
The prevalence of type 2 diabetes mellitus has been
increasing rapidly worldwide [1], making knowledge of
risk factors and protective factors associated with type 2
diabetes mellitus essential for the development of preven-
tion strategies.
Results from animal and human studies suggest an
improvement in glucose and insulin sensitivity during
lactation [2–5]. Data from two large cohorts in the USA
also indicate that longer duration of breast-feeding may
reduce the risk of type 2 diabetes mellitus by improving
glucose homeostasis [6].
We examined the association between lifetime breast-
feeding and the incidence of type 2 diabetes mellitus in a
large population-based cohort study of middle-aged women,
the Shanghai Women’s Health Study (SWHS).
Diabetologia (2008) 51:258–266
DOI 10.1007/s00125-007-0885-8
R. Villegas:G. Yang:W. Zheng:X.-O. Shu (*)
Vanderbilt Epidemiology Center,
Institute for Medicine and Public Health,
Department of Medicine, Vanderbilt University Medical Center,
2525 West End Avenue, Suite 600,
Nashville, TN 37232-1738, USA
e-mail: xiao-ou.shu@vanderbilt.edu
Y.-T. Gao:H. L. Li
Department of Epidemiology, Shanghai Cancer Institute,
Shanghai, People’s Republic of China
T. Elasy
Diabetes Research and Training Center,
Vanderbilt University Medical Center,
Nashville, TN, USA

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Methods
Study population The SWHS is a population-based pro-
spective cohort study of middle-aged women (40–70 years
old) conducted in seven urban communities of Shanghai,
China. Details of the SWHS survey have been reported
elsewhere [7]. From a total of 81,170 women who were
invited to participate, 75,221 were recruited (92.7%
participation rate). Reasons for non-participation were
refusal (3.0%), absence during the enrolment period
(2.6%) and other reasons (health, hearing, speaking prob-
lems; 1.6%). After exclusion of women younger than
40 years or older than 70 years at the time of interview
(n=278), 74,942 women remained for the study. Partic-
ipants completed a detailed survey as part of an in-person
interview, which included assessment of dietary intake,
physical activity, measurement of anthropometrics and
other lifestyle factors. The original questionnaires, in
Chinese, are available from the corresponding author upon
request. Protocols for the SWHS were approved by the
Institutional Review Boards of all institutes involved in the
study and written informed consent was obtained prior to
interview. Biannual in-person follow-up of all living cohort
members was conducted by in-home visit from 2000 to
2002 and from 2002 to 2004, with a response rate of 99.8
and 98.7%, respectively; only 934 participants were lost to
follow-up.
Outcome ascertainment Incident type 2 diabetes mellitus
was identified through follow-up surveys. A total of 1,561
parous women reported a type 2 diabetes mellitus diagnosis
since the baseline survey. For the current study we
considered a case of type 2 diabetes mellitus to be
confirmed if the participants reported having been diag-
nosed with type 2 diabetes mellitus and met at least one of
the following criteria: fasting glucose level ≥7 mmol/l on at
least two separate occasions or an oral glucose tolerance
test with a value ≥11.1 mmol/l and/or use of hypoglycaemic
medication (i.e. insulin or oral hypoglycaemic drugs). All
tests were performed as part of patients’ primary care. Of
the self-reported cases, a total of 869 participants met the
study outcome criteria and are referred to herein as
confirmed cases of type 2 diabetes mellitus. We performed
analyses restricted to confirmed cases as well as analyses
including all cases of type 2 diabetes mellitus.
Breast-feeding duration assessment Information on each
pregnancy was obtained during the in-person interview.
This included date and outcome of each pregnancy and
whether and for how long the participant breastfed each
child. Based on this information, we calculated the duration
of breast-feeding (months and years) and duration of breast-
feeding per live birth (years).
Measurement of potential confounders Anthropometric
measurements were taken at baseline recruitment according
to a standard protocol by trained interviewers who were
retired medical professionals [8]. Self-reported body weight
history was obtained for ages 20 and 40 years and at
baseline recruitment. We calculated BMI (weight in kg
divided by the square of height in m), WHR (waist
circumference divided by hip circumference) and stan-
dardised weight change (difference between measured
weight at baseline and weight at 20 years divided by the
interval between study recruitment and 20 years; kg/year).
A structured questionnaire was used at the baseline
survey to collect information on socio-demographic factors
such as age, level of education (none, elementary school,
middle/high school, college), family income in yuan per
year (<10,000, 10,000–19,999, 20,000–29,999, >30,000),
occupation (professional, clerical, manual labour/other,
housewife/retired), smoking (smoked at least one cigarette
per day for more than 6 months continuously) and alcohol
consumption (had ever drunk beer, wine or spirits at least
three times per week). History of diseases such as diabetes,
cancer, cardiovascular disease and high blood pressure was
also collected.
Information on physical activity was obtained using a
validated questionnaire [9]. The questionnaire evaluated
exercise and sport participation, daily activity and daily
commuting round-trip journey to work. We calculated the
metabolic equivalents (METs) for each activity, using a
compendium of physical activity values [10]. We derived a
quantitative estimate of overall non-occupational activity
(MET-h per day).
Dietary intake was assessed through an in-person
interview using a validated food frequency questionnaire
at the baseline recruitment survey and at the first follow-up
survey [11]. The Chinese food composition tables [12] were
used to estimate energy intake (kJ/day).
Statistical analysis Person-years for each participant were
calculated as the interval between the baseline recruitment
to one of the following: diagnosis of type 2 diabetes
mellitus; censored at death; or completion of the second
follow-up survey.
The Cox proportional hazards model was used to assess
the effect of breast-feeding on the incidence of type 2
diabetes mellitus. Tests for trend were performed by
entering the categorical variables as continuous parameters
in the models. In all models, we adjusted for the following
potential confounding variables: age, BMI, WHR, total
energy, physical activity, number of live births (entered as
continuous variables), income level, education level,
occupation, smoking status, alcohol consumption status
and presence of hypertension at baseline (as categorical
variables).
Diabetologia (2008) 51:258–266 259

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We also derived a propensity score by regressing breast-
feeding (yes/no) on risk factors for type 2 diabetes mellitus
(age, daily energy intake, BMI, WHR, smoking, alcohol
consumption, physical activity, hypertension, income, edu-
cation level, occupation status, oral contraceptive use,
vegetable intake, legume intake, meat intake and staples
intake). We then examined the association between breast-
feeding (yes/no) and type 2 diabetes mellitus by including
the propensity score in the Cox proportional hazard model.
All analyses were performed using SAS (version 9.1, SAS
Institute, Cary, NC, USA), and all tests of statistical
significance were based on two-sided probability. A p
value of less than 0.05 was considered statistically
significant.
Results
The average age of the entire SWHS cohort (n=74,942)
was 52.1 (SD=9.1). The average age at first pregnancy was
25.5 years (median: 25.7 years) and the median number of
Table 1 Age-standardised characteristics of parous women in the Shanghai Women’s Health Study by duration of breast-feeding
Duration of breast-feeding (months)
0 >0 to 6>6 to 11 >11 to 35
≥36p value for
trenda
Women (n)
Cases of diabetes (n)
Person-years (n)
<10 years since last pregnancy (%)
Age, median (Q25–Q75)
Energy intake, mean kJ/day (SE)
Live births, median (Q25–Q75)
BMI, mean kg/m2(SE)
WHR, mean (SE)
Weight gain, mean kg/year (SE)
Weight at age 20 years, median kg
(Q25–Q75)
Smoker (%)
Ever drinker (%)
Exercise (%)
High physical activityb(%)
Education (%)
None
Elementary
Middle/high school
College
Household income (%)
<10,000 yuan
10,000–19,999 yuan
20,000–29,999 yuan
>30,000 yuan
Occupation (%)
Professional
Clerical
Manual labour/others
Housewife/retired
Hypertension (%)
11,395
225
53,038
26.9
45 (42–49)
6,875 (14)
1 (1–1)
23.4 (0.03)
0.80 (0.0005)
0.34 (0.003)
48 (45–53)
10,463
163
48,770
21.9
45 (42–49)
6,927 (15)
1 (1–1)
23.2 (0.03)
0.8 (0.0005)
0.31 (0.003)
49 (45–53)
14,958
253
69,741
28.9
45 (42–49)
6,920 (13)
1 (1–1)
23.6 (0.03)
0.80 (0.0005)
0.33 (0.003)
50 (45–54)
18,144
585
83,870
18.6
54 (49–61)
6,985 (11)
2 (1–2)
24.2 (0.02)
0.81 (0.004)
0.36 (0.003)
50 (45–54)
7,135
335
32,535
3.7
64 (62–67)
6,738 (21)
4 (3–5)
24.7 (0.04)
0.82 (0.007)
0.37 (0.005)
50 (45–55)
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
1.7 (1.5–1.9)
1.9 (1.7–2.1)
30.5 (29.5–31.5)
22.8 (22.0–23.6)
1.4 (1.2–1.9)
2.1 (1.9–2.3)
32.9 (31.9–33.9)
22.1 (21.3–22.9)
1.5 (1.3–1.7)
2.1 (1.9–2.3)
34.3 (33.3–35.3)
24.4 (21.6–25.2)
2.4 (2.3–2.5)
2.4 (2.3–2.5)
33.7 (32.7–34.7)
27.3 (26.9–27.7)
3.6 (3.2–4.0)
1.9 (1.7–2.1)
31.4 (30.4–32.4)
41.2 (40.2–42.2)
<0.001
<0.001
0.18
<0.001
11.0 (12.4–11.6)
38.2 (37.2–39.2)
32.5 (31.5–33.5)
18.3 (17.5–19.1)
8.5 (7.9–9.1)
34.4 (33.4–35.4)
34.3 (33.3–35.3)
22.7 (21.9–23.5)
9.6 (9.0–10.2)
39.2 (38.2–40.2)
32.4 (31.4–33.4)
18.8 (18.0–19.6)
17.8 (17.4–18.2)
44.3 (43.8–44.8)
27.1 (26.7–27.5)
10.8 (10.5–11.1)
41.2 (40.2–42.2)
46.9 (47.9–48.9)
8.6 (8.0–9.2)
3.3 (2.9–3.7)
<0.001
14.0 (13.4–14.6)
38.8 (37.8–39.8)
29.4 (28.5–30.3)
17.8 (17.0–18.6)
11.6 (11.0–12.2)
35.8 (34.8–36.8)
31.3 (30.3–32.3)
21.4 (20.6–22.4)
12.6 (12.0–13.2)
37.1 (36.1–38.1)
30.4 (29.4–31.4)
19.8 (19.0–20.6)
15.6 (15.3–15.9)
38.0 (37.5–38.5)
28.6 (28.2–29.0)
17.8 (17.4–18.2)
22.1 (21.3–22.9)
38.7 (37.7–39.7)
27.8 (27.0–28.6)
11.4 (10.8–12.0)
<0.001
21.6 (20.8–22.4)
12.8 (12.2–13.4)
21.8 (21.0–22.6)
43.8 (42.8–44.8)
18.4 (17.6–19.2)
25.9 (25.1–26.7)
12.4 (11.6–12.8)
21.0 (20.2–21.8)
40.7 (39.7–41.7)
18.3 (17.5–19.1)
22.2 (21.4–23.0)
13.2 (12.6–13.8)
23.1 (22.3–23.9)
41.6 (40.6–42.6)
18.8 (18.0–19.6)
16.4 (15.6–17.2)
13.7 (13.4–14.0)
23.6 (23.2–24.0)
46.3 (45.8–46.8)
19.8 (19.4–20.2)
6.8 (6.2–7.4)
19.5 (18.7–20.3)
20.0 (19.2–20.8)
53.6 (52.6–54.6)
16.6 (15.8–17.4)
<0.001
0.12
Data are presented as n, percent, median (Q25–Q75, interquartile range) and mean (SE), and are directly standardised in years to the age
distribution of the population
Means of energy intake, BMI, WHR and standard weight are adjusted by age
Weight at 20 years and number of live births were not normally distributed and could not be adjusted for age
ap values for trend were calculated by: proportional odds model for prevalence of population characteristics; ANOVA test for daily energy intake,
BMI, WHR and standard weight gain; and Kruskal–Wallis test for age, number of live births and weight at 20 years
bHigh physical activity: participants in the upper quartile of total METs
260Diabetologia (2008) 51:258–266

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live births was 1.0. A total of 3.3% women had no children,
54.4% had only one child, 21.2% had two children, 10.5%
had three children, 6.2% had four children and 4.3% had
five or more children. The incidence of diabetes mellitus
was 6.0 cases per 1,000 person-years at risk.
There were 62,095 parous women in this study with no
prior history of type 2 diabetes mellitus, cancer or cardio-
vascular disease at study recruitment; of these 50,700
(81.65%) reported having breastfed their children. The
average number of live births was 1.7, the average number
of months of breast-feeding was 14.6 and the average
number of years of breast-feeding per child was 0.6. The
number of live births was associated with months of breast-
feeding (Spearman correlation coefficient, 0.70; p<0.001).
Age-standardised characteristics of the study population by
duration of breast-feeding are shown in Table 1. Women
with a longer duration of breast-feeding were older, had less
education, lower income and were less likely to be
employed at the time of the survey or to hold a professional
job. Duration of breast-feeding was also associated with
smoking and higher physical activity in this population. We
did not find an association between differences in partici-
pation in exercise or prevalence of hypertension at baseline
and duration of breast-feeding (p>0.05).
Women who had breastfed tended to have a lower risk of
type 2 diabetes mellitus [relative risk (RR)=0.88; 95% CI,
0.76–1.02; p=0.08] than women who had never breastfed,
in analyses adjusted for age, daily energy intake, BMI,
WHR, number of live births, occupation, income levels,
education, smoking, alcohol consumption, physical activity
and presence of hypertension (Table 2). When we adjusted
the analysis by a propensity score of predictors of type 2
diabetes mellitus, the RR was 0.81 (95% CI, 0.70–0.94;
p<0.01).
The duration of breast-feeding and duration of breast-
feeding per child were associated with a lower risk of type
2 diabetes mellitus (Table 2). The fully adjusted RR for 0,
>0 to 0.99, >0.99 to 1.99, >1.99 to 2.99, >2.99 to 3.99 and
≥4 years of breast-feeding with the risk of type 2 diabetes
mellitus were 1.00, 0.88, 0.89, 0.88, 0.75 and 0.68. The
fully adjusted RR between years of breast-feeding per child
and type 2 diabetes mellitus risk were 1.00, 0.91, 0.87 and
0.87 (p=0.11 for trend) for 0, >0 to 0.49, >0.49 to 0.99 and
≥1 years of breast-feeding per number of births. Associa-
tions between months of breast-feeding and incidence of
type 2 diabetes mellitus are presented in Table 3. BMI and
WHR are the two major confounding factors for the
association between the duration of breast-feeding and risk
of type 2 diabetes mellitus. Both BMI and WHR were
weakly correlated with breast-feeding (r=0.22 and 0.22,
respectively). The correlation between BMI and WHR was
0.46. The association between the duration of breast-
feeding and diabetes mellitus was accentuated and the
trend was only marginally significant when we adjusted the
model for BMI. Additional adjustment for WHR resulted in
the trend becoming statistically significant (p=0.04). The
association between breast-feeding and type 2 diabetes
mellitus did not change much after adjustment for number
of live births. When we restricted the analysis of breast-
feeding and incidence of type 2 diabetes to confirmed cases
of type 2 diabetes mellitus, we found similar patterns of
association (Table 4).
Table 2 Associations between type 2 diabetes mellitus and duration of breast-feeding for all participants, Shanghai Women’s Health Study
% Cases per person-yearsRR95% CIp value for trend
Breast-feeding
No
Yes
Duration of breast-feeding
Years
0
>0–0.99
>0.99–1.99
>1.99–2.99
>2.99–3.99
≥4
Years per child
0
>0–0.49
>0.49–0.99
≥1
18.35
81.65
225/53,038
1,336/234,916
1.00
0.88 0.76–1.02
18.35
47.99
17.31
7.57
4.15
4.63
225/53,038
416/118,511
343/57,418
242/26,451
148/14,929
187/17,606
1.00
0.88
0.89
0.88
0.75
0.68
0.01
0.75–1.04
0.75–1.06
0.71–1.07
0.59–0.96
0.52–0.90
18.35
15.10
44.20
22.35
225/53,038
200/43,615
659/127,453
477/63,848
1.00
0.91
0.87
0.87
0.11
0.75–1.10
0.74–1.02
0.78–1.03
Values are adjusted for age, daily energy intake, BMI, WHR, number of live births, smoking, alcohol consumption, physical activity, education,
income, occupation and hypertension
Diabetologia (2008) 51:258–266261

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In analyses restricted to women who reported having been
pregnant within the last 10 years (Table 5), the RR for type 2
diabetes mellitus by the duration of breast-feeding per
number of live births was 1.00, 1.01, 0.74 and 0.65; (p=
0.03 for trend) for 0, >0 to 0.49, >0.49 to 0.99 and ≥1 years
of breast-feeding per number of live births. Among women
who had been pregnant within the last 10 years, the RRs of
type 2 diabetes mellitus for 0, >0 to 0.99, >0.99 to 1.99,
>1.99 to 2.99, >2.99 to 3.99 and ≥4 years of breast-feeding
were 1.00, 0.80, 0.78, 0.58, 0.47 and 0.45 (p=0.04 for
trend). The RRs of type 2 diabetes mellitus for 0, >0 to 0.99,
>0.99 to 1.99, >1.99 to 2.99, >2.99 to 3.99 and ≥4 years of
breast-feeding among women who had been pregnant within
the last 5 years were 1.00, 0.87, 0.68, 0.44, 0.69 and ≥0.49
(p=0.02 for trend; data not shown in tables). In addition, we
found that the RRs for diabetes mellitus associated with
≥12 months of breast-feeding were 0.66 (95% CI, 0.45–
0.95), 0.63 (95% CI, 0.40–0.98), 0.49 (95% CI, 0.28–0.85)
and 0.46 (95% CI, 0.26–0.86), respectively, when analyses
were conducted with time since last pregnancy defined as
≤13, ≤10, ≤5 and ≤2 years (data not shown). In analyses
restricted to women who had not been pregnant in the last
10 years, we still found inverse associations between breast-
feeding and risk of type 2 diabetes mellitus, although the
associations between months of breast-feeding and years of
breast-feeding per child were not significant. The association
between years of breast-feeding and type 2 diabetes mellitus
was of marginal significance. The RRs of type 2 diabetes
mellitus for 0, >0 to 0.99, >0.99 to 1.99, >1.99 to 2.99,
>2.99 to 3.99 and ≥4 years of breast-feeding were 1.00, 0.90,
0.94, 0.94, 0.79 and 0.72 (p=0.06 for trend). Similar trends
were found when the analysis was restricted to confirmed
Table 3 Incidence of type 2 diabetes by duration of breast-feeding, Shanghai Women’s Health Study
0 >0 to 6 months>6 to 11 months>11 to 35 months
≥36 months
RR 95% CI RR95% CI RR95% CI RR 95% CI RR 95% CIp value for trend
Model 1
Model 2
Model 3
Model 4
Model 5
Model 6
1.00
1.00
1.00
1.00
1.00
1.00
0.81
0.84
0.84
0.87
0.89
0.87
0.66–0.99
0.69–1.03
0.69–1.03
0.71–1.06
0.71–1.06
0.71–1.06
0.88
0.89
0.88
0.91
0.89
0.89
0.74–1.07
0.74–1.07
0.73–1.05
0.76–1.09
0.74–1.07
0.75–1.07
1.08
0.99
0.90
0.98
0.89
0.89
0.92–1.27
0.85–1.18
0.76–1.05
0.83–1.15
0.76–1.05
0.75–1.05
1.03
0.88
0.76
0.84
0.75
0.73
0.84–1.25
0.71–1.08
0.62–0.93
0.68–1.03
0.61–0.92
0.58–0.91
0.20
0.75
0.06
0.39
0.04
0.05
Model 1 age-adjusted only; Model 2: age plus other confounders, but not BMI, WHR or number of live births; Model 3: model 2 plus BMI;
Model 4: model 2 plus WHR; Model 5: model 2 plus BMI and WHR; Model 6: model 5 plus number of live births
Table 4 Associations between
type 2 diabetes mellitus and
duration of breast-feeding,
Shanghai Women’s Health
Study (confirmed cases of dia-
betes only)
Values are adjusted for age,
daily energy intake, BMI,
WHR, number of live births,
smoking, alcohol consumption,
physical activity, education,
income, occupation and
hypertension
% Cases per person-yearsRR95% CI p value
Breast-feeding
No
Yes
Duration of breast-feeding
Months
0
>0–6
>6–11
>11–35
>36
Years
0
>0–0.99
>0.99–1.99
>1.99–2.99
>2.99–3.99
>4
Years per child
0
>0–0.49
>0.49–0.99
>1
18.40
81.60
128/52,848
741/233,836
1.00
0.87
0.17
0.72–1.06
18.40
16.91
24.21
29.11
11.37
128/52,848
86/48,617
159/69,558
314/83,398
182/32,263
1.00
0.80
0.98
0.84
0.74
0.17
0.61–1.05
0.77–1.24
0.68–1.05
0.55–1.01
18.40
48.20
17.25
7.48
4.10
4.57
128/52,848
297/11,817
200/57,156
99/26,242
65/14,809
78/17,454
1.00
0.91
0.90
0.72
0.72
0.67
0.01
0.73–1.13
0.72–1.13
0.54–0.95
0.52–1.01
0.46–0.96
18.40
15.13
44.21
22.25
128/52,848
116/43,443
359/126,916
266/63,447
1.00
0.94
0.84
0.88
0.23
0.73–1.21
0.69–1.04
0.70–1.11
262Diabetologia (2008) 51:258–266