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Epidemiology

Work Stress, Obesity and the Risk of Type 2

Diabetes: Gender-Specific Bidirectional Effect
in the Whitehall II Study
Alexandros M. Heraclides1,2, Tarani Chandola1,3, Daniel R. Witte1,2 and Eric J. Brunner1
Psychosocial work stress has been linked to higher risk of type 2 diabetes (T2DM), with the effect being consistently
higher among women than men. Also, work stress has been linked to prospective weight gain among obese men but
weight loss among lean men. Here, we aimed to examine the interaction between work stress and obesity in relation to
T2DM risk in a gender-specific manner. We studied 5,568 white middle-aged men and women in the Whitehall II study,
who were free from diabetes at analysis baseline (1993). After 1993, diabetes was ascertained at six consecutive
phases by an oral glucose tolerance test supplemented by self-reports. Cox regression analysis was used to assess
the association between job strain (high job demands/low job control) and 18-year incident T2DM stratifying by BMI
(BMI <30kg/m2 vs. BMI 30kg/m2). Overall, work stress was associated with incident T2DM among women (hazard
ratio (HR) 1.41: 95% confidence intervals: 1.02; 1.95) but not among men (HR 0.87: 95% confidence interval 0.69;
1.11) (PINTERACTION = 0.017). Among men, work stress was associated with a lower risk of T2DM in nonobese (HR 0.70:
0.53; 0.93) but not in obese individuals (PINTERACTION = 0.17). Among women, work stress was associated with higher
risk of T2DM in the obese (HR 2.01: 1.06; 3.92) but not in the nonobese (PINTERACTION = 0.005). Gender and body weight
status play a critical role in determining the direction of the association between psychosocial stress and T2DM. The
potential effect-modifying role of gender and obesity should not be ignored by future studies looking at stress-disease
associations.
Obesity (2011) 20, 428433. doi:10.1038/oby.2011.95

Introduction

The psychosocial hypothesis of chronic disease is centered on the

notion that the social environment has the capacity to elicit adverse
psychological reactions and that repeated exposure to these has
cumulative physiological impact (1,2). In addition, chronic stressors could increase disease risk through an unhealthier lifestyle
and subsequent weight gain. Psychosocial stress at work has previously been linked to heart disease (35), obesity (6,7), the metabolic syndrome (8), and type 2 diabetes (T2DM) (911).
We have previously shown that women experiencing psychosocial work stress have twice the risk of T2DM compared
to women with no work stress (12). Excess body fat accumulation, for which BMI is a relatively accurate surrogate, has been
linked to profound endocrine changes related to T2DM (13).
Previous evidence from our study suggests that psychosocial
work stress is associated with prospective weight gain among
obese men but prospective weight loss among lean men (14).
Given this evidence, we hypothesized that body weight status

modifies the effect of psychosocial work stress on incident

T2DM, in a gender-specific manner.
Our aim was to examine the association between work stress
and T2DM among a sample of British, middle-aged men and
women, stratifying by gender and BMI.
Methods and Procedures
Setting and population
The Whitehall II study is an occupational cohort established in 1985
with the broad aim of investigating the social gradient in disease outcomes. At study baseline (19851988) 10,308 participants aged 3555
years were recruited from 20 civil service departments in London, UK.
After the initial clinical examination, further waves of data collection
were carried out in 1989 (phase 2), 19911993 (phase 3, including a
clinical examination), 1995 (phase 4), 19971999 (phase 5, clinical
examination), 2001 (phase 6), 20022004 (phase 7, clinical examination), 2006 (phase 8) and 20082009 (phase 9, clinical examination).
The participation rate at phases 3, 5, 7, and 9 (clinical examination
phases) was 85%, 71%, 68%, and 66%, respectively. The number of participants in the clinical examination at phase 9 was 6,755. The partici-

1
Department of Epidemiology and Public Health, Royal Free and University College London Medical School, London, UK; 2Diabetes Epidemiology Group,
Steno Diabetes Center, Gentofte, Denmark; 3School of Social Sciences, The Cathie Marsh Centre for Census and Survey Research, University of Manchester,
Manchester, UK. Correspondence:Alexandros Heraclides (axhr@steno.dk)

Received 13 August 2010; accepted 14 March 2011; published online 19 May 2011. doi:10.1038/oby.2011.95

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pants lost to follow-up were more likely to be women and to come from
the lower employment grades, were slightly older, had a slightly higher
BMI and had a higher prevalence of work stress at baseline.
The current analysis includes 5,138 white participants (3,689 men and
1,449 women) free from diabetes at baseline and with valid data on incident diabetes, psychosocial work stress and all the covariates used in the
multivariate analysis (sub-section following). Ethical approval for the
study was obtained from the Joint UCL/UCLH Committees on the Ethics
of Human Research. All participants gave written informed consent for
participation at each phase.
Assessment of glycemia and ascertainment of diabetes
At phase 3 (19911993), venous blood samples were taken from fasting
individuals (8h of fasting) before undergoing a standard 2-h oral glucose tolerance test (75g anhydrous glucose over 5min). Glucose samples were drawn into fluoride monovette tubes which were centrifuged
on site within 1h. Plasma or serum was immediately removed from
the monovette tubes, and moved into microtubes and stored at 70C.
Blood glucose was measured with the glucose oxidase method (15) on
YSI model 23A glucose analyzer (mean coefficient of variation at phase
3 2.93.3%) (16) and YSI model 2300 STAT PLUS analyzer (phases 5
and 7 mean coefficient of variation 1.43.1%) (17) (YSI Corporation,
Yellow Springs, OH). Subsequent clinical assessments for diabetes took
place at phases 5, 7, and 9. The definition of diabetes used was a 2-h
glucose tolerance test finding of at least 200mg/dl (11.1mmol/l) or
a fasting glucose level of 126mg/dl (7.0mmol/l) (18) or physiciandiagnosed diabetes and/or use of diabetic medication.
Psychosocial work stress
The Job Strain Questionnaire was developed to provide an integrating
theoretical framework for stress-related job characteristics that can be
assessed for the full workforce (19). In more detail, the questionnaire
assessed the aggregate of psychological stressors affecting work (job
demands) and the individuals potential control over job-related decision making (decision latitude).
In the Whitehall study, job demands (4 items; Cronbachs = 0.67) and
decision latitude (15 items; Cronbachs = 0.84) were measured using the
main questions from the Job Strain Questionnaire (19). The empirical
association between components of the Job Strain Questionnaire and
psychological strain has been previously demonstrated in relation to
depression, sleeping problems, and exhaustion (19).
According to the original demands/control model, high job demands
were identified as above the median score and low job control as below
the median score for the specific sample. Job strain was present when
the participant simultaneously scored high on the job demands (above
median score) and low on the decision latitude scales (below median
score) (19).
BMI and other covariates
Weight was measured by a Soehnle scale to the nearest 0.1kg with all
items of clothing removed except underwear. Height was measured to
the nearest mm using a stadiometer with the participant standing completely erect with the head in the Frankfort plane. BMI was calculated
as weight (kg) divided by height (m) squared. Obesity was classified
according to the World Health Organization definition (20).
Participants reported their Civil Service grade title, which was assigned
to 1 of 6 grades based on salary scale. In the British civil service employment grade is an accurate measure of status, income and employment
relations and hence socioeconomic position (21). Participants were asked
to report how much they were upset from personal illness, death or illness
of a close relative or friend, major financial difficulty, divorce, separation
or break of a personal intimate relationship, other marital or family problem, experience of a mugging, robbery, accident or similar event. From
these questions, a variable scored from 0 to 21 was developed measuring the extent by which participants were upset by life events outside
work during the recent past. Other social, psychosocial, and psychological variables (such as marital status, neighborhood deprivation, anger,
obesity | VOLUME 20 NUMBER 2 | february 2012

hostility, social isolation, minor psychiatric morbidity) were available

in the Whitehall II study and were considered as potential confounders/mediators but none of these was linked to job strain, thus were not
included in the analysis.
Participants reported the frequency of eating a common portion size of
each item of a 127-item semi-quantitative food frequency questionnaire.
Dietary patterns were identified in sex-specific cluster analysis (PROC
FASTCLUS; SAS Institute, Cary, NC). The four clusters identified were:
(i) healthy; (ii) Mediterranean-like; (iii) sweet; and (iv) unhealthy (22).
Participants reported the number of units of beer, wine or spirits they
had consumed in the last 7 days. Units of alcohol (8g) consumed per
week were based on the Sensible drinking recommendations for adults
in the UK (23) as: no consumption, moderate consumption (128 units/
week in men; 121 in women) and heavy consumption (>28 units/week
in men; >21 in women). Frequency and duration of mild, moderate, and
vigorous activities were self-reported and hours per week of activity at
the three intensity levels was calculated as metabolic equivalenthours/
week. Participants were asked about their smoking status. Participants
who reported smoking at phase 3 were defined as current smokers. Those
who reported not smoking at phase 3 (and were not identified as current
or ex-smokers in previous phases) were classified as never smokers. Exsmokers were those participants who reported past smoking at phase 3
or current or ex-smoking at previous phases.
Clinical measurements were carried out according to a standard protocol (24). Blood pressure was measured in the sitting position using a
Hawksley random zero sphygmomanometer. Venous blood was taken in
the fasting state or at least 5h after a light, fat-free breakfast. Serum triglycerides were measured by automated enzymatic colorimetric methods.
High-density lipoprotein cholesterol was measured using phosphotungstate precipitation.
Statistical analysis
Multivariate Cox proportional hazards regression analysis was used
to examine the associations between job strain and 18-year incident
T2DM. The date of ascertainment of each T2DM case was taken as the
mid-point between the date of T2DM identification during data collection (clinical examination or questionnaire) and the date of the previous data collection. Participants were censored at the time of loss to
follow-up or at the end of 2004 (phase 7). Type 2 diabetes cases and
the censored participants contributed their follow-up time to the overall person-years at risk for the period from 1991 to 2004. Schoenfeld
residuals were plotted against follow-up time for testing the proportional hazards assumption (25). All P values were nonsignificant, confirming that the proportional hazards assumption was justified. Hazard
ratios (HRs) presented are relative risks for type 2 diabetes comparing
participants exposed to job strain to participants not exposed, adjusting for age, socioeconomic position (employment grade), diet pattern,
physical activity, alcohol consumption, smoking status, systolic blood
pressure, triglycerides, and high-density lipoprotein cholesterol.
The analysis was stratified by BMI, assessing the effect of job strain
on incident T2DM among obese (BMI 30kg/m2) and nonobese (BMI
<30kg/m2) participants. The likelihood ratio test was used to statistically
test for an interaction between job strain and BMI. The interaction was
tested with BMI both as a continuous term (multiplicative interaction)
and a binary (i.e., presence of obesity) term. Analysis was performed
separately in men and women for investigating gender-specific interactions between stress and obesity.
Results

During an 18-year follow-up (19912009) and 114,447 personyears at risk, 927 new T2DM cases were identified. The 18-year
incidence of T2DM was 8.10 (95% confidence interval: 7.59;
8.64). Participants diagnosed with T2DM during follow-up
were older, more likely to be in the low employment grade,
were more upset by life events outside work and had a higher
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Table 1 Baseline (19911993) characteristics of the 5,138 participants included in analysis stratified by psychosocial work stress
Job strain (n = 1,387)

No job strain (n = 3,751)

Agemean (s.e.)*

48.7 (0.08)

49.1 (0.35)

Women (%)**

34.2 (474)

26.6 (998)

Low employment gradea (%)**

15.2 (211)

13.4 (503)

No university degree (%)**

39.1 (542)

28.6 (1,073)

Upset by life events scoremean (s.e.)**

3.13 (0.08)

2.74 (0.05)

Unhealthy diet pattern (%)**

34.7 (481)

32.2 (1,208)

Alcohol abstainer (%)*

12.4 (172)

9.0 (338)

Current smoking (%)*

15.6 (216)

12.3 (461)

Physical activity (METh/day)mean (s.e.)*

3.41 (0.04)

3.58 (0.07)

BMI (kg/m2)mean (s.e)

25.5 (0.9)

25.5 (0.5)

Waist circumference (cm)mean (s.e.)*

85.6 (0.30)

86.7 (0.17)

119.6 (0.33)

121.0 (0.21)

Triglycerides (mmol/l)mean (s.e.)

1.46 (0.03)

1.48 (0.02)

HDL-cholesterol (mmol/l)mean (s.e.)

1.42 (0.01)

1.42 (0.01)

C-reactive protein (mg/l)mean (s.e.)

1.88 (0.11)

1.87 (0.06)

Systolic blood pressure (mm Hg)mean (s.e.)**

HDL, high-density lipoprotein; MET, metabolic equivalent.

a
Makes the table self-explanatory. bProvides level of significance.
*P < 0.05, **P < 0.01.
Nonobese

Obese

1.00
Job strain
0.90

Survival probability

No job strain
No job strain

0.80

0.70
Job strain
0.60

0.50
0

10

12

14

16

18

20

10

12

14

16

18

20

Follow-up (years)

Figure 1 Kaplan-Meier curves showing cumulative survival probabilities for incident type 2 diabetes by baseline job strain during 18 years of followup among nonobese and obese participants (men + women) in the Whitehall II study.

BMI, systolic blood pressure, triglycerides and lower highdensity lipoprotein cholesterol (characteristics of the phase 3
Whitehall II sample stratified by follow-up diabetes status can
be found elsewhere) (12).
Table1 shows baseline characteristics of the 5,138 participants with data on all covariates included in analysis (540 incident T2DM cases) stratified by exposure to work stress (job
strain). The prevalence of job strain in this sample at analysis
baseline was 27% (25% in men and 32% in women). Compared
to participants with no job strain, those with baseline job
strain were slightly older, more likely to be women and to come
from a lower employment grade, had an unhealthier lifestyle
430

in terms of diet, alcohol intake patterns, physical activity and

smoking, and were more upset by life events outside work.
Participants with job strain did not have a worse cardiometabolic risk profile (BMI and blood lipids) compared to those
with no job strain and in fact had lower waist circumference
and systolic blood pressure. Other baseline characteristics (see
Methods and Procedures section) were considered as potential
confounders/mediators but are not presented in Table1 as they
were not linked to job strain and not included in analysis.
Figure1 displays KaplanMeier curves showing estimates
for the age-adjusted survival probability for 18-year incident
T2DM by job strain among nonobese (BMI <30kg/m2) and
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Table 2Hazard ratios (95% confidence intervals (CIs)) for the association between job strain and incident type 2 diabetes by BMI
All men
Cases/total

Nonobese men (BMI <30kg/m2)

HR (95% CI)

389/3,689

0.80 (0.63; 1.02)

All women

Cases/total
151/1,449

Cases/total

HR (95% CI)

310/3,429

0.70 (0.53; 0.93)

Nonobese women (BMI <30kg/m2)

Obese men (BMI 30kg/m2)

Cases/total

HR (95% CI)

P for interactiona

79/260

1.05 (0.63; 1.75)

0.17

Obese women (BMI 30kg/m2)

HR (95% CI)

Cases/total

HR (95% CI)

Cases/total

HR (95% CI)

P for interactiona

1.37 (0.98; 1.92)

104/1,248

1.18 (0.63; 2.10)

47/201

2.01 (1.06; 3.82)

0.005

Adjusted for age, employment grade, diet pattern, alcohol consumption, physical activity, smoking status, systolic blood pressure, triglycerides, high-density lipoprotein
cholesterol. Comparing participants with and without job strain (no job strain is the reference category).
a
Interaction between job strain and BMI tested both with the continuous and binary (BMI <30kg/m2 vs. BMI 30kg/m2) variables with similar results (P values presented
are for the continuous variable).

Obese YES/
Stress YES
Obese YES/
Stress NO
Obese NO/
Stress YES
Obese NO/
Stress NO

Hazard ratio (95% CI)

Figure 2 Hazard ratios (95% confidence intervals (CIs)) for the effect
of job strain on 18-year incident type 2 diabetes after cross-classifying
participants by body weight status and exposure to work stress
among men.

Obese YES/
Stress YES
Obese YES/
Stress NO
Obese NO/
Stress YES
Obese NO/
Stress NO

Hazard ratio (95% CI)

Figure 3 Hazard ratios (95% confidence intervals (CIs)) for the effect
of job strain on 18-year incident type 2 diabetes after cross-classifying
participants by body weight status and exposure to work stress
among women.

obese participants (BMI 30kg/m2). The KaplanMeier curves

indicate that the probability of surviving (i.e., not developing
diabetes) differed by baseline job strain only among obese participants, thus providing an initial suggestion for an interaction between work stress and obesity.
Table2 shows multivariate adjusted HRs (n = 5,138; 540 incident diabetes cases) for the association between baseline job
strain and 18-year incident T2DM stratifying by BMI separately
in men and women. Among men, job strain was associated
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with a lower risk of T2DM in the nonobese (HR0.70: 95% confidence intervals 0.53; 0.93) but not in the obese (PINTERACTION
= 0.17). In contrast, among women, job strain was associated
with higher risk of type 2 diabetes in the obese (HR 2.01: 1.06;
3.92) but not in the nonobese (PINTERACTION = 0.005). This analysis was repeated stratifying by overweight and obesity (BMI
25kg/m2 vs. BMI <25kg/m2) as well as for central obesity
(waist circumference >102cm for men and >88cm for women;
Adult Treatment Panel III definition). In both cases very similar results to those reported in Table2 were obtained.
Figures 2 and 3 show HRs for incident T2DM cross-classifying participants by work stress (job strain) and obesity (BMI
30kg/m2) in men and women, respectively. Participants not
exposed to work stress and who were not obese served as the
reference category in this analysis. As expected, among both
men and women, the obese had a higher risk of T2DM compared to the nonobese. Among men, the nonobese stressed had
lower risk of T2DM than the nonobese nonstressed (Figure2).
Among women, the obese stressed had higher risk of T2DM
than the than the obese nonstressed (Figure3). The risk associated with co-occurrence of obesity and work stress among
women was over and above the risk associated with the two
exposures individually.
Discussion
Summary of findings

In this sample of middle-aged British civil servants, the association between work stress and incident T2DM was modified
by BMI differentially among men and women. Work stress
was associated with a lower risk of T2DM among nonobese
men, while it was associated with a higher risk of T2DM
among obese women. There was no evidence for an association between work stress and T2DM among obese men and
nonobese women.
The major strength of the current analysis is the accurate
assessment of all key factors (psychosocial stress, obesity and
diabetes). The Whitehall II study was specifically designed to
assess the impact of psychosocial factors on chronic disease
and thus assessment of psychosocial work stress is detailed and
comprehensive. Diabetes was ascertained by an oral glucose
tolerance test at consecutive phases, which is rare for a population-based epidemiological study. Obesity was also accurately
assessed using weight and height measured by trained nurses.
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In addition, the prospective design and long follow-up of the
study allows for a detailed investigation of long-term diabetes
risk using a large number of incident cases.
Some weaknesses of the current analysis are the self-reported
nature of the exposure of interest (psychosocial work stress)
and the fact that only a single assessment at one point of time
was used here. However, despite being based on subjective
data, the job strain measure has been linked to indicators of
psychological strain such as depression, sleeping problems,
and exhaustion (12). Another weakness is the substantial loss
to follow-up, which differed by baseline exposure to work
stress and was more apparent for obese women. If however
this was a potential source of bias it would have led to a type
II error (failing to find an existent association) rather than
a type I error (finding an association that dos not exist). In
the current results, the magnitude of the effect of work stress
among women was relatively big and it may have been even
bigger if the obese, stressed women who were lost to follow-up
remained in the study.

tective effect of work stress on incident T2DM among men is

most likely due to prospective weight loss associated with work
stress among lean men, as reported in a previous publication
from our research group (14). In that analysis, being exposed
to work stress was associated with weight loss during a 5-year
follow-up among lean men but not lean women, which supports the current finding of lower risk of diabetes among nonobese stressed men but not nonobese stressed women. Even
though stress-related excessive weight loss, especially among
already lean individuals, is by no means healthy overall, it
seems to be protective for T2DM development at least. The
reasons for the absence of stress-related weight loss and hence
lower risk of T2DM among women in our study need further
investigation and this finding is not necessarily applicable to
the general population.

Framingham Offspring study, obesity was related differentially

to cardiometabolic risk factors among men and women (29).
Evidence for sex differences in the development of T2DM, especially in relation to activation of the innate immunity, has been
shown consistently in the German MONICA/KORA study (30,
31). In addition, there is some evidence for gender-specific psychoneuroendocrine activation with women being more prone
to the health impact of chronic psychosocial stress (3235).
Among a sub-sample from the Whitehall II study, men and
women had similar salivary cortisol levels during the weekends
but women had significantly higher cortisol levels compared
to men in working days (36). Similar results of gender-specific
cortisol responses to chronic work stress have been observed
in an Italian (37) and a German (38) study. In addition, work
stress was linked to decreased heart rate variability (a measure
of impaired autonomic activity) among women but not men in
a Finnish study (39). In the Whitehall II study, sleep deprivation
was linked to higher incidence of hypertension among women
but not men (40). This is of importance as sleep deprivation activates the same neuroendocrine pathways as stress and in fact
may be a potential mediating factor in the gender differences
observed in the current paper. Unfortunately data on sleep duration were not available at the baseline of the current analysis,
thus this variable could not be included as a potential mediator.
There may also be a social element in the gender-specific
stressobesity interaction. Obese individuals may be carrying
the additional psychosocial burden of discrimination due to
their body weight status, making them more vulnerable to other
psychosocial stressors (i.e., work stressors). Such discriminations associated with obesity may be felt more strongly among
obese women than obese men (41). Exposure to work stress may
therefore be an additional burden among obese women. In addition, in the Whitehall II study, women as a whole are more likely
to accumulate exposure to work stress during follow-up, while
the opposite holds for men, who are more likely to escape from
work stress through the years compared to women. This chronic
exposure to stress could provide an explanation for the overall
gender differences observed, with higher effects among women.

The harmful effect among obese women. The main biological

Conclusion

Potential explanations for the gender-specific

stressobesity interaction
The protective effect among nonobese men. The observed pro-

candidate for explaining the stressobesity interaction in relation to T2DM is the stress-hormone cortisol (26). Cortisol can
interfere in the normal regulation of blood glucose by altering
the bodys release and sensitivity to insulin, thus increasing the
risk of T2DM (1,2). In a recent publication from the Whitehall
study (27), the slope of the diurnal release of cortisol was shallower among obese individuals, highlighting a possible defect
in the functioning of the hypothalamic-pituitary-adrenal axis
of the stress response. Given that cortisol levels are elevated by
exposure to psychosocial stressors (28), a plausible explanation
for the observed effect is that stress-related elevations in cortisol
levels carry a bigger pathophysiological burden among obese
than nonobese individuals.
The observation that obesity modifies the effect of work stress
on T2DM only among women could be explained by genderspecific pathways involved in pathogenesis of T2DM. In the
432

The protective effect of psychosocial work stress on T2DM risk

among nonobese men probably reflects the prospective weight
loss related to stress among lean individuals. On the other
hand, the harmful effect of psychosocial work stress among
obese women probably reflects gender-specific psychoneuroendocrine pathways as well as additional discrimination due
to increased body mass. To our knowledge, this is the first study
to report the prospective effect of psychosocial work stress on
incident T2DM stratifying by BMI. Overall the current results
suggest that the stress-obesity-diabetes triangle is complex and
gender-specific. We suggest that future investigations on the
effect of psychosocial work stress on cardiometabolic disease
are performed stratifying by gender and body weight status.
Further elucidation of the involvement of psychosocial stress
in obesity and diabetes could inform strategies aiming to prevent both diseases.
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Acknowledgments
The Whitehall II study was supported by grants from the Medical Research
Council; Economic and Social Research Council; British Heart Foundation;
Health and Safety Executive; Department of Health; National Heart Lung
and Blood Institute (HL36310), US, NIH; National Institute on Aging
(AG13196), US, NIH; Agency for Health Care Policy Research (HS06516);
and the John D and Catherine T MacArthur Foundation Research Networks
on Successful Midlife Development and Socioeconomic Status and Health.
We thank all participating civil service departments and their welfare,
personnel, and establishment officers; the Occupational Health and Safety
Agency; the Council of Civil Service Unions; all participating civil servants in
the Whitehall II study; and all members of the Whitehall II study team.

Disclosure
The authors declared no conflict of interest.
2011 The Obesity Society

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