‏إظهار الرسائل ذات التسميات factors. إظهار كافة الرسائل
‏إظهار الرسائل ذات التسميات factors. إظهار كافة الرسائل

الاثنين، 3 سبتمبر 2012

Lifestyle, social factors, and survival after age 75: population based study

Lifestyle, social factors, and survival after age 75: population based study | BMJ

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Research Lifestyle, social factors, and survival after age 75: population based study BMJ 2012; 345 doi: 10.1136/bmj.e5568 (Published 30 August 2012) Cite this as: BMJ 2012;345:e5568 Health education Health promotion Smoking Smoking and tobacco Sociology Epidemiologic studies More topics

Sports and exercise medicine Fewer topics

Article Related content Read responses (1) Article metrics Debora Rizzuto, PhD student1, Nicola Orsini, associate professor2, Chengxuan Qiu, associate professor1, Hui-Xin Wang, senior researcher1, Laura Fratiglioni, professor13
1Aging Research Center, Department of Neurobiology, Health Care Sciences and Society, Karolinska Institutet and Stockholm University, 113 30 Stockholm, Sweden
2Unit of Nutritional Epidemiology and Unit of Biostatistics, National Institute of Environmental Medicine, Karolinska Institutet
3Stockholm Gerontology Research Center, StockholmCorrespondence to: D Rizzuto debora.rizzuto{at}ki.seAccepted 13 August 2012AbstractObjective To identify modifiable factors associated with longevity among adults aged 75 and older.

Design Population based cohort study.

Setting Kungsholmen, Stockholm, Sweden.

Participants 1810 adults aged 75 or more participating in the Kungsholmen Project, with follow-up for 18 years.

Main outcome measure Median age at death. Vital status from 1987 to 2005.

Results During follow-up 1661 (91.8%) participants died. Half of the participants lived longer than 90 years. Half of the current smokers died 1.0 year (95% confidence interval 0.0 to 1.9 years) earlier than non-smokers. Of the leisure activities, physical activity was most strongly associated with survival; the median age at death of participants who regularly swam, walked, or did gymnastics was 2.0 years (0.7 to 3.3 years) greater than those who did not. The median survival of people with a low risk profile (healthy lifestyle behaviours, participation in at least one leisure activity, and a rich or moderate social network) was 5.4 years longer than those with a high risk profile (unhealthy lifestyle behaviours, no participation in leisure activities, and a limited or poor social network). Even among the oldest old (85 years or older) and people with chronic conditions, the median age at death was four years higher for those with a low risk profile compared with those with a high risk profile.

Conclusion Even after age 75 lifestyle behaviours such as not smoking and physical activity are associated with longer survival. A low risk profile can add five years to women’s lives and six years to men’s. These associations, although attenuated, were also present among the oldest old (=85 years) and in people with chronic conditions.

IntroductionAn increasing proportion of the population in the developed countries lives to very advanced age.1 Although our current knowledge on the determinants of longevity is limited, the general consensus is that longevity is a multifactorial quantitative trait that is influenced by biological, environmental, and psychosocial factors.2 Among all these elements, modifiable risk factors are especially relevant as they are amenable to intervention. Lifestyle, social networks, and leisure activities have been studied individually in relation to longevity in several studies and others have examined the possible association of these factors with longevity while taking into account their coexistence and interactions.3 4 5 6 7 8 9 10 11 12 13 14 Only a few studies, however, have examined the relation between the combinations of various modifiable factors and longevity.15 16 17 Among the previous studies that have included the oldest old population (=85 years),8 9 10 11 12 13 14 15 16 17 only four had an observational period longer than 10 years.8 9 12 16

Briefly, studies have shown that lifestyle factors such as smoking,3 4 10 11 13 14 16 alcohol consumption,3 4 and body weight (both underweight and overweight),8 16 can predict mortality in elderly people. However, it is uncertain whether these associations are applicable to the oldest old. Indeed, studies have indicated that the relation between certain lifestyle factors and mortality may differ among those aged 75 or older compared with younger adults.7 8 9 14 16 Results concerning the association between social network and mortality among the elderly population have been controversial.18 Finally, previous reports have supported the hypothesis that the associations between leisure time activity, especially physical activity,4 5 6 12 13 16 and survival among the elderly population are positive, although these relations have not been confirmed in other studies.11

We examined the associations of independent and combinations of various modifiable factors with median age at death in a cohort aged 75 or more years at entry to the Kungsholmen Project in central Stockholm, Sweden, that was followed for 18 years. Unlike previous studies that reported the associations in terms of relative risks or hazard ratios, we used absolute values, such as differences in survival among different groups.

MethodsThe study was carried out as part of the Kungsholmen Project, a community based longitudinal study on aging and dementia. A detailed description of the study population and the baseline survey has been previously published.19 20 Briefly, the initial cohort included all registered inhabitants in the Kungsholmen district of central Stockholm who were aged 75 years or older at baseline (October 1987). Of the 2368 eligible participants living at home or in institutions, 181 died, 69 moved out of the area before the baseline examination, and 308 refused to participate, leaving 1810 participants (76.4%) who undertook the baseline survey for the current analysis.

Data collectionData on personal characteristics (age, sex, occupation, and education) at baseline was obtained from participants through a face to face interview with trained nurses, following standard protocols.19 20 Educational level was measured as total years of formal schooling. Socioeconomic status was evaluated on the basis of both education and occupation. Education was divided into primary (<8 years) and secondary or above (=8 years). We used a questionnaire developed by an expert in occupational medicine to assess occupation based socioeconomic status. Information collected about lifetime work activities included employer, job title, period of employment, and tasks for all jobs lasting at least six months. We grouped lifetime occupational experiences according to the Swedish socioeconomic classification system.21 The main occupation was defined as the longest job during lifetime, classified as manual work or non-manual work.22

Information on smoking and alcohol consumption was obtained from baseline data or, if information was missing at baseline, from data collected at the first follow-up three years after baseline. Smoking history was assessed by asking participants whether they had ever smoked. Smokers and former smokers were asked how long they had smoked and the number of cigarettes smoked per day. Former smokers were also asked at what age they had stopped smoking. We categorised smoking status as current, former, and never.23

Alcohol consumption was categorised as yes or no. At baseline, only 6% of the participants reported being heavy drinkers (>168 g ethanol per week for men and >112 g ethanol per week for women). We calculated body mass index as weight (kg) divided by the square of the height (m) using direct measures, and we used standard cut-offs to categorise the participants as overweight (body mass index >25), of normal weight (20-25), or underweight (<20).24

Information on leisure activities and social networks was obtained from participants through face to face interviews carried out by trained nurses during the baseline survey.19 20 Participants were asked whether they regularly engaged in any particular activities or belonged to any organisations. If so, they were asked to specify the types of activities or organisations and to report the frequency of participation. We grouped the reported activities into mental, physical, social, and productive according to the classification adopted in previous studies.25 The frequency of participation in any leisure activities was initially recorded as daily, weekly, monthly, or annually. On the basis of the answers, we categorised the frequency as no participation, daily to weekly participation, and monthly participation. Owing to the statistical power of the study, we analysed survival in relation to participation in each type of activity (at least monthly) compared with no participation. Participants were assigned to a particular group if they participated in at least one of that group’s activities. Mental activities included reading books or newspapers, writing, studying, doing crossword puzzles, painting, or drawing. Physical activities encompassed swimming, walking, or gymnastics. Social activities consisted of attending the theatre, concerts, or art exhibitions; traveling; playing cards or games; or participating in social groups or an organisation for older people. Productive activities included gardening, housekeeping, cooking, working for pay after retirement, doing volunteer work, and sewing, knitting, crocheting, or weaving.

To determine the extent of social networks, we asked participants about marital status, living arrangements, parenthood, and friendships. We also asked about frequency of contact with children and friends or relatives and how satisfied participants were with the frequency of those contacts. On the basis of their answers, we grouped the participants into the three social network categories of rich, moderate, and limited or poor.26 The group with a rich social network included those who were married and lived with someone, had children with whom they were in daily to weekly contact and found this level of contact satisfactory, and had relatives or friends with whom they were in daily to weekly contact and found this level of contact satisfactory. The group with a moderate social network included those who had any two of the three elements. The group with a limited or poor social network included those who had any one or none of the three elements.

If participants were not able to answer the questions (for example, they had cognitive impairment or dementia), then we interviewed an informant, usually someone who was next of kin.

We classified a disease as chronic if it had one or more of the following characteristics: was permanent; was caused by non-physiological changes leading to irreversible damage to a tissue, organ, or system; required rehabilitation; or required a long period of care.27 Multimorbidity was defined as the existence of two or more chronic diseases in one individual; we did not define index diseases.28 We ascertained the participants’ history of chronic diseases using the computerised Stockholm inpatient register system, which covers the period 1969 to 1989 (before baseline). The International Classification of Diseases (eighth revision) was used for all diagnoses in the inpatient register system.

Information about the vital status of the participants in 2005 was derived from death certificates provided by Statistics Sweden.

Statistical analysisAs participants entered in the study at various ages, we analysed baseline age as a confounder and not as a main exposure of interest in the analyses.

The median age at death was the age at which half of the participants had died and the other half were still alive. Survival time was censored for those who were still alive at the end of the study (31 August 2005). We used Laplace regression to model the median age at death as a function of lifestyle factors, leisure activities, and social network.29 Firstly, we estimated differences in median age at death separately by each modifiable factor in age adjusted models. Secondly, we simultaneously adjusted for all the modifiable factors and personal characteristics that were statistically significant in the age adjusted models. Because elderly people often experience chronic illnesses that can affect their lifestyle, we further adjusted for number of chronic conditions.28

Laplace regression is a statistical model that makes inferences on centiles (for example, median) of survival time conditionally on covariates, while taking into account the presence of censored observations. In the absence of covariates, Laplace regression provides estimates of survival centiles similar to the non-parametric Kaplan-Meier method. However, unlike Kaplan-Meier analysis, Laplace regression allows researchers to model the association between continuous exposures, adjusting for confounders, and to assess interactions in predicting survival time.30

The proportion of missing covariate data was 4% for leisure activities, 19% for body mass index, 28% for smoking, and 32% for alcohol consumption. We carried out a complete case analysis based on 60% of the cohort. A sensitivity analysis was done for missing data, with multivariate imputation by chained equations (MICE) to obtain 50 imputed datasets.31 We pooled the estimates using Rubin’s rule to obtain valid statistical inferences.32 All the relevant variables included in the major analyses were used in the multiple imputation models, as was the outcome (age at death).

In the secondary analysis we investigated the relation between various combinations of modifiable factors and median age at death. We defined a reference group as participants with a high risk profile. This group included all participants who had unhealthy lifestyle factors (were overweight or underweight and were current or former smokers), a limited or poor social network, and did not engage in any leisure activities. We estimated median age at death for this group and then compared this with the median age at death for three other groups: those with a moderately high risk profile, those with a moderately low risk profile, and those with a low risk profile. The moderately high risk profile included those participants with at least two of the three risk factors and therefore included those active in at least one leisure activity but who had a poor or limited social network and unhealthy lifestyle factors; or those with a moderate or rich social network but who had unhealthy lifestyle factors and were not engaged in any leisure activities; or those with healthy lifestyle factors (normal weight and never smoked) but who had a limited or poor social network and were not engaged in any leisure activities. The moderately low risk profile included those with only one of the three risk factors and therefore included those active in at least one leisure activity and with a moderate or rich social network but with unhealthy lifestyle factors; or those with a moderate or rich social network and healthy lifestyle factors but who were not engaged in any leisure activities; or those with healthy lifestyle factors who were active in at least one leisure activity but who had a limited or poor social network. The low risk profile included those who had healthy lifestyle factors, had a rich or moderate social network, and engaged in at least one leisure activity.

ResultsTable 1? shows the personal characteristics, lifestyle factors, extent of social networks, leisure activities, and health status of the participants by survival status at 18 years of follow-up. The mean (standard deviation) age at the end of follow-up was 96.1 (3.0) years for survivors and 89.5 (5.4) years for non-survivors. Survivors were more likely than non-survivors to be women, be highly educated, have healthy lifestyle factors, have a better social network, and participate in more leisure activities.

View this table:View PopupView InlineTable 1 Characteristics of study population by survival status at 18 years of follow-up

During the 18 years of follow-up, 149 (8.2%) participants survived and 1661 (91.8%) did not. Overall, 50% of the participants lived to be 90.0 years or older (median age at death).

Table 2? shows the differences in median age at death across the potentially relevant factors. In the age adjusted models, median age at death for participants of normal weight or who had never smoked was about one year longer than those who were underweight (difference in median age at death -1.1, 95% confidence interval -1.7 to -0.4) and current smokers (-1.3, -2.2 to -0.4). Participants who consumed alcohol survived a median of 1.3 years (95% confidence interval 0.7 to 1.8) longer than never drinkers. Half of the participants with a rich social network lived at least 1.6 years (95% confidence interval 0.8 to 2.5) longer than those with a limited or poor social network. Of all the leisure activities, physical activity was associated with the largest difference in median survival; those who were physically active survived more than two years longer than those who were physically inactive (differences in median age at death 2.3 years, 95% confidence interval 1.5 to 3.1).

View this table:View PopupView InlineTable 2 Differences in median age at death (95% confidence intervals) at 18 year follow-up

The multivariable model controlled for all factors that were significantly associated with survival in the age adjusted models. The associations between most factors and survival remained similar in direction and magnitude, except for rich social network and mental activity where the differences in median survival were no longer statistically significant. Further adjustment for multimorbidity attenuated the differences in median survival. Social network did not follow this pattern, as after controlling for multimorbidity people with a rich social network clearly survived longer than people with a limited or poor social network. The magnitude and direction of the differences in median age at death based on the main analysis of complete data and the sensitivity analysis of multiple imputations were similar (table 2).

Table 3? shows the differences in median age at death between the group with the high risk profile (reference group) and the other three groups. The figure? shows the median age at death in all four groups for the entire population and stratified by sex, age at baseline, and number of chronic conditions. Overall, after age 75, lifestyle behaviours such as never smoking, participating in at least one leisure activity, and having frequent contact with children or friends and relatives (and being satisfied with this contact) were associated with survival. Median survival for those in the group with the low risk profile was almost five years longer than that in the group with the high risk profile (table 3). The median age at death was about 83 years for those with a high risk profile and 88 years for those with a low risk profile (figure). Stratified analysis by sex showed that the median age at death was higher for women than for men. The difference in median age at death between people with a low risk profile and those with a high risk profile was six years for men and five years for women (table 3). Stratification by age showed that even in the oldest old participants (=85 years) the median age at death was higher (4.7 years more) if participants belonged to the group with the low risk profile (table 3).

Finally, stratified analysis by health conditions revealed that the median age at death for participants with more than one chronic condition who belonged to the group with the low risk profile was 87 years, around five years older than those in the group with the high risk profile (median age at death 82 years, figure)

View larger version:In a new windowDownload as PowerPoint SlideMedian age at death in four risk groups according to combinations of modifiable factors among entire population, men and women separately, older adults (75-84 years) and oldest old adults (=85 years), and by status of chronic conditions. Results were from Laplace regression, adjusted for education

View this table:View PopupView InlineTable 3 Differences in median age at death at 18 years of follow-up for four risk profile groups, in entire population and in strata by sex, age groups, and health status

DiscussionIn this longitudinal study of 1810 older participants followed up for 18 years, several lifestyle behaviours were associated with longevity, even after age 75 and independently of health status. Certain health behaviours remained predictive of survival even among the oldest old (=85 years) and those with multimorbidity. To the best of our knowledge this is the first study that directly provides information about differences in longevity according to several modifiable factors.

Lifestyle factors and survivalSmokers who survived to 75 years had a one year shorter median survival than those who had never smoked. In the Kungsholmen Project population, 83% of the former smokers had quit smoking 15 to 35 years before baseline and 17% had quit five to 14 years before baseline. The pattern of survival in all former smokers in the study population was the same as that of never smokers. In line with our results, previous studies have found an inverse association between smoking and survival among elderly people,11 13 16 whereas other studies have failed to find an association.8 9 12 Our results confirm the negative association between smoking and survival even in old age, and that quitting smoking in middle age reduces the effect on mortality. Because most former smokers in the study had quit smoking 15 to 35 years before baseline, it is not clear if quitting smoking five to 14 years before baseline may still be associated with survival in elderly people, although this seems to be suggested by our results.

Leisure activities and survivalThe positive association between leisure activity, especially regular physical activity, and longevity found in our analysis confirms the results of some previous studies12 13 16 but not others.11 Although the present analysis cannot provide a definite answer about whether the association between lack of physical activity and shorter survival reflects the effect of illness present at baseline, we were able to minimise the confounding effect by adjusting for morbidity and multimorbidity at baseline. After adjustment the association between physical activity and survival was still significant. Moreover, we cannot verify whether physical activity levels reported at baseline were important in themselves or were indicators of an individual’s lifetime history of physical activity.

Combinations of modifiable factors and survivalOur results on the associations between various combinations of modifiable factors and median age at death showed that compared with their respective high risk profile groups, men with a low risk profile gained more years of survival than women with a low risk profile: the women by five years and the men by six years. Even among those aged 85 years or more, the median age at death could be four years higher if the participants had a healthy lifestyle, a rich or moderate social network, and engaged in at least one leisure activity. Finally, the median age at death for people with more than one chronic condition but who belonged to the group with the low risk profile was 87 years, five years later than those with a high risk profile.

Only a few studies have investigated the relation between combinations of modifiable factors and survival. In the Survey in Europe on Nutrition and the Elderly: a Concerted Action (SENECA) study, researchers developed a lifestyle score by combining three lifestyle factors (non-smoking, physical activity, and quality of diet) and found a strong relation between a healthy lifestyle score and survival.15 Another study pooled five healthy behaviours (based on smoking, alcohol consumption, diet, body mass index, and physical activity) and investigated the relation between this group of healthy behaviours and mortality. They found that the hazard ratio in men with a low lifestyle score was statistically higher than in men with a high lifestyle score.17 Researchers working with the Physicians’ Health Study cohort found that the probability of surviving to age 90 was 54% for those with no adverse factors (those who had never smoked, had normal blood pressure and weight, did not have diabetes, and were moderately physically active).16 Our results were similar to the results of those studies in which the probability of survival was significantly higher among those with the healthier lifestyle scores than among those with less healthy lifestyle scores.

Strengths and limitations of the studyThe major strengths of our study were that the study population was from the general population, including people living at home and in institutions; the study design was prospective; the data on extensive modifiable factors were substantial; and follow-up was long-term. Additionally, we accounted for possible reverse causality by considering only the baseline ascertainment of chronic conditions. All previous studies have examined variation in the risk, hazard, or rate ratio of mortality in relation to selected modifiable factors. The interpretation of these commonly used measures of association may not be easy to communicate to patients or to the general public.

The drop-out rate at baseline of the Kungsholmen Project was 23.6% (558/2368), mainly due to refusal (12.4%), death (7.6%), and moving from the area (3.6%). The personal characteristics of those who refused to participate and those who moved did not differ from those of the participants. Only the 181 who dropped out due to death differed from participants, as they were older and more often men. It is likely that those drop-outs led to an overestimation of the median age at death, especially for the oldest old (=85 years) men.

Any interpretation of the results needs to take survival selection into account33 (in this case before age 75). This is especially true for factors that show an inverse association with mortality. The positive associations with mortality are more likely to be simply underestimated. On the other hand, our study population included people who survived to at least 75 years, which enabled us to investigate the associations of independent and combinations of various modifiable factors with survival in a very old population (=75 years). This is particularly relevant given the limited current knowledge about the relations between such modifiable factors and longevity.

In our study only a small proportion of people had a high alcohol consumption. Thus alcohol consumption, which was mostly moderate, may have protected against mortality. However, because of the high rate of missing data (32%) we cannot rule out the possibility that this result may be heavily affected by information bias.34

Although we adjusted for many factors potentially associated with longevity, our analysis did not include all variables that may be associated with longevity (such as quality of diet). Further analyses are also needed to examine the association between incident morbidity and survival. Moreover, we could not assess the relations between changes in modifiable factors over the lifespan and survival because we assessed exposures only at baseline. Furthermore, repeated measurements of exposure would have provided a better understanding about whether accumulation of factors over the lifetime affects the associations between lifestyle or social factors and survival. In addition, whether extra years of life gained through increased longevity are spent in good or bad health is a crucial question, which we did not address in this study.

Ignoring missing data in complete case analysis can potentially lead to biased estimates.35 However, the small differences in the results of complete case and multiple imputation analyses in this study suggest that missing data had little impact on the observed findings.

ConclusionsThe associations between leisure activity, not smoking, and increased survival still existed in those aged 75 years or more, with women’s lives prolonged by five years and men’s by six years. These associations, although attenuated, were still present among people aged 85 or more and in those with chronic conditions. Our results suggest that encouraging favourable lifestyle behaviours even at advanced ages may enhance life expectancy, probably by reducing morbidity.

What is already known on this topicLifestyle factors such as smoking, alcohol consumption, and being underweight or overweight predict mortality among the elderly population

It is uncertain whether these associations are applicable to the oldest old (=85 years) because of mixed results

What this study addsLifestyle behaviours such as smoking and physical activity predict survival even after age 75

The associations of leisure activity and not smoking with increased life expectancy were still present among those aged 85 or more and those with chronic conditions

NotesCite this as: BMJ 2012;345:e5568

FootnotesWe thank the members of the Kungsholmen Project study group for data collection and Kimberly Kane (scientific editor) for useful comments on the text.

Contributors: DR and LF designed the study. DR and NO did the statistical analyses. DR drafted the manuscript. All authors critically revised the manuscript for important and intellectual content. DR is the guarantor.

Funding: This study was funded by the Swedish Council for Working Life and Social Research, Swedish Research Council for Medicine, Swedish Brain Power, Karolinska Institutet’s Faculty funding for postgraduate students, and the Stiftelsen Ragnhild och Einar Lundströms Minne. The sponsor had no role in study design, data collection, data analysis, data interpretation, the writing of the report, or in the decision to submit the paper for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.

Ethical approval: This study was approved by the ethics committee of Karolinska Institutet, and informed consent was obtained from all participants (87:148; 87:234; 90:251; 94:122, 97:413, and 99:308).

Data sharing: No additional data available.

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Weight-modification trials in older adults: what should the outcome measure be? Curr Control Trials Cardiovasc Med2002;3:1.OpenUrlCrossRefMedline?Wang HX, Karp A, Winblad B, Fratiglioni L. Late-life engagement in social and leisure activities is associated with a decreased risk of dementia: a longitudinal study from the Kungsholmen project. Am J Epidemiol2002;155:1081-7.OpenUrlFREE Full Text?Fratiglioni L, Wang HX, Ericsson K, Maytan M, Winblad B. Influence of social network on occurrence of dementia: a community-based longitudinal study. Lancet2000;355:1315-9.OpenUrlCrossRefMedlineWeb of Science?Timmreck TC, Cole GE, James G, Butterworth DD. Health education and health promotion: a look at the jungle of supportive fields, philosophies and theoretical foundations. Health Educ1987;18:23-8.OpenUrlMedline?Marengoni A, Angleman S, Melis R, Mangialasche F, Karp A, Garmen A, et al. Aging with multimorbidity: a systematic review of the literature. Ageing Res Rev2011;10:430-9.OpenUrlCrossRefMedlineWeb of Science?Bottai M, Zhang J. Laplace regression with censored data. Biom J 52:487-503.?Orsini N, Wolk A, Bottai M. Evaluating percentiles of survival. Epidemiology2012;23:770-1.OpenUrlCrossRefMedline?Van Buuren S, Boshuizen HC, Knook DL. Multiple imputation of missing blood pressure covariates in survival analysis. Stat Med1999;18:681-94.OpenUrlCrossRefMedlineWeb of Science?Rubin DB, Schenker N. Multiple imputation for interval estimation from simple random samples with ignorable nonresponse. J Am Stat Assoc1986;81;366-74.?Glymour MM, Weuve J, Chen JT. Methodological challenges in causal research on racial and ethnic patterns of cognitive trajectories: measurement, selection, and bias. Neuropsychol Rev2008;18:194-213.OpenUrlCrossRefMedlineWeb of Science?Huang W, Qiu C, Winblad B, Fratiglioni L. Alcohol consumption and incidence of dementia in a community sample aged 75 years and older. J Clin Epidemiol2002;55:959-64.OpenUrlCrossRefMedlineWeb of Science?Demissie S, LaValley MP, Horton NJ, Glynn RJ, Cupples LA. Bias due to missing exposure data using complete-case analysis in the proportional hazards regression model. 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Contribution of modifiable risk factors to social inequalities in type 2 diabetes: prospective Whitehall II cohort study

Contribution of modifiable risk factors to social inequalities in type 2 diabetes: prospective Whitehall II cohort study | BMJ

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Research Contribution of modifiable risk factors to social inequalities in type 2 diabetes: prospective Whitehall II cohort study BMJ 2012; 345 doi: 10.1136/bmj.e5452 (Published 21 August 2012) Cite this as: BMJ 2012;345:e5452 Diabetes Metabolic disorders Health policy Health service research Sociology Epidemiologic studies Health education More topics

Health promotion Diet Hypertension Smoking Smoking and tobacco Obesity (nutrition) Obesity (public health) Fewer topics

Article Related content Article metrics Silvia Stringhini, research fellow1, Adam G Tabak, clinical research associate23, Tasnime N Akbaraly, senior research fellow245, Séverine Sabia, research associate2, Martin J Shipley, senior lecturer2, Michael G Marmot, professor of epidemiology and director2, Eric J Brunner, reader2, G David Batty, Wellcome Trust fellow26, Pascal Bovet, professor of epidemiology and public health1, Mika Kivimäki, professor of social epidemiology2
1Institute of Social and Preventive Medicine, Lausanne University Hospital, 1010 Lausanne, Switzerland
2University College London, Department of Epidemiology and Public Health, London, UK
3Semmelweis University, Faculty of Medicine, 1st Department of Medicine, Budapest, Hungary
4Inserm U1061, Montpellier, France
5Université Montpellier I, Montpellier, France
6MRC Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UKCorrespondence to: S Stringhini silvia.stringhini{at}chuv.chAccepted 25 July 2012AbstractObjective To assess the contribution of modifiable risk factors to social inequalities in the incidence of type 2 diabetes when these factors are measured at study baseline or repeatedly over follow-up and when long term exposure is accounted for.

Design Prospective cohort study with risk factors (health behaviours (smoking, alcohol consumption, diet, and physical activity), body mass index, and biological risk markers (systolic blood pressure, triglycerides and high density lipoprotein cholesterol)) measured four times and diabetes status assessed seven times between 1991-93 and 2007-09.

Setting Civil service departments in London (Whitehall II study).

Participants 7237 adults without diabetes (mean age 49.4 years; 2196 women).

Main outcome measures Incidence of type 2 diabetes and contribution of risk factors to its association with socioeconomic status.

Results Over a mean follow-up of 14.2 years, 818 incident cases of diabetes were identified. Participants in the lowest occupational category had a 1.86-fold (hazard ratio 1.86, 95% confidence interval 1.48 to 2.32) greater risk of developing diabetes relative to those in the highest occupational category. Health behaviours and body mass index explained 33% (-1% to 78%) of this socioeconomic differential when risk factors were assessed at study baseline (attenuation of hazard ratio from 1.86 to 1.51), 36% (22% to 66%) when they were assessed repeatedly over the follow-up (attenuated hazard ratio 1.48), and 45% (28% to 75%) when long term exposure over the follow-up was accounted for (attenuated hazard ratio 1.41). With additional adjustment for biological risk markers, a total of 53% (29% to 88%) of the socioeconomic differential was explained (attenuated hazard ratio 1.35, 1.05 to 1.72).

Conclusions Modifiable risk factors such as health behaviours and obesity, when measured repeatedly over time, explain almost half of the social inequalities in incidence of type 2 diabetes. This is more than was seen in previous studies based on single measurement of risk factors.

IntroductionDiabetes is a major cause of morbidity and premature mortality worldwide.1 2 In 2011 the World Health Organization estimated that as many as 346 million people lived with the disease, 90% of whom had type 2 diabetes.3 In addition to its own treatment burden, which exacts enormous healthcare expenditure,4 type 2 diabetes is also an established risk factor for cardiovascular diseases,5 selected cancers,6 and possibly mood disorder and dementia.7 Thus, identification of those groups at increased risk of type 2 diabetes, together with an understanding of the mechanisms involved, remains a public health priority. Research has now established that the occurrence of type 2 diabetes is not evenly distributed across society: in high income countries, the lower socioeconomic groups are disproportionately affected.8 9 10 11 12 However, much remains to be learnt about the modifiable risk factors that contribute to socioeconomic variations in type 2 diabetes.

Differences in the availability or affordability of healthy foods or places to exercise, differential access to healthcare services and health information, and differences in health related behaviours between socioeconomic groups have all been proposed as potential explanations for the social patterning of type 2 diabetes.13 14 Among these, physical inactivity, obesity, unhealthy diet, and cigarette smoking are established risk factors for the development of the disease and have been shown to be more prevalent among the disadvantaged socioeconomic groups.15 16 17 18 19 20 They are thus potentially important mediators of the association between socioeconomic status and type 2 diabetes. However, previous studies suggest that these factors can explain only about a third of social inequalities in type 2 diabetes.10 12 21 22

In a recent study in the British Whitehall II cohort, we showed that health behaviours explain a greater proportion of social inequalities in mortality when they are assessed repeatedly over the follow-up rather than at baseline only.23 Most studies on type 2 diabetes offer only a one-off measurement of health behaviours, so previous studies may have underestimated their contribution. In this study, we used data from the Whitehall II cohort to assess the contribution of smoking, alcohol consumption, dietary behaviours, physical activity, and body mass index to social inequalities in the incidence of type 2 diabetes. We compared their role when they were assessed at study baseline or repeatedly over the follow-up and when long term exposure was accounted for. Furthermore, we evaluated the additional contribution of biological risk markers for type 2 diabetes that are commonly measured in clinical settings: systolic blood pressure, triglycerides, and high density lipoprotein cholesterol.

MethodsStudy population and designThe Whitehall II study was established in 1985 among 10?308 (3413 women) London based civil servants aged 35-55 years.24 The first examination (phase 1) took place during 1985-88 and involved a clinical examination and a self administered questionnaire. A 75 g oral glucose tolerance test was done for the first time at phase 3 (1991-93; n=8815) and repeated at phase 5 (1997-99), phase 7 (2003-04), and phase 9 (2007-09). Therefore, the phase 3 examination is the baseline for the analyses we report here. We included participants free of type 2 diabetes at phase 3 and followed them for incident diabetes up to phase 9. Additional questionnaire only phases also assessed diabetes status at phase 4 (1995-96), phase 6 (2001), and phase 8 (2006).

Socioeconomic statusSocioeconomic status was based on participants’ occupational position at phase 3 and categorised into high (administrative), intermediate (professional/executive), and low (clerical/support). This measure is a comprehensive marker of socioeconomic circumstances and is related to education, salary, social status, and level of responsibility at work.24 25

Diabetes risk factors and risk markersHealth behaviours were assessed at phases 1, 3, 5, and 7. Current smoking was self reported and classified as yes/no. Alcohol consumption was assessed by using questions on the number of alcoholic drinks consumed in the previous week, then converted to number of alcohol units consumed per week and categorised as “abstainers” (0 units/week), “moderate drinkers” (1-21/1-14 units/week for men/women), or “heavy drinkers” (=21/=14 units/week for men/women).26

Overall diet was assessed by calculating a score of adherence to healthy dietary guidelines provided by the alternative healthy eating index.27 28 This index was based on intake levels of vegetables, fruit, nuts, and soy, white to red meat ratio, total fibre, trans fat, polyunsaturated to saturated fatty acids ratio, long term multivitamin use, and alcohol consumption.28 The score was then trichotomised on the basis of tertiles. As the alternative healthy eating index was not available for phase 1, a diet score was calculated by using information on fruit and vegetable intake and the type of bread and milk most commonly consumed, as described previously.23

Physical activity was assessed by using questions on the frequency and duration of participation in moderate or vigorous physical activity at phases 1 and 3. At phases 5 and 7, the questionnaire included 20 items on frequency and duration of participation in different physical activities that were used to calculate hours per week at each intensity level.29 Participants were classified as “active” (=2.5 hours/week of moderate or =1 hour/week of vigorous physical activity), “inactive” (=1 hour/week of moderate and =1 hour/week of vigorous physical activity), or “moderately active” (if not active or inactive).

Height and weight were measured at phases 1, 3, 5, and 7 by following standard procedures. Body mass index was then calculated and categorised in three groups (normal, <25; overweight, 25-29; obese, =30) on the basis of WHO recommendation.30

Biological risk markers related to type 2 diabetes were drawn from phases 1, 3, 5, and 7 and categorised into high and low risk groups.31 32 High triglycerides were defined as =1.7mmol/L and low high density lipoprotein cholesterol as <1.0 mmol/L in men and <1.2 mmol/L in women. High systolic blood pressure was defined as =140 mm Hg. At phase 1, high density lipoprotein cholesterol measurements were available for only 1208 participants and triglycerides for only 1758. We predicted missing high density lipoprotein cholesterol data by using data on apolipoprotein A I, as described previously.33 Cumulative exposure to high triglycerides concentrations between phases 1 and 3 could not be assessed.

Ethnicity was drawn from phase 1 and categorised as white/non-white. Family history of type 2 diabetes (parents and siblings) was self reported at phases 1 and 2 and categorised as yes/no.

Incident type 2 diabetesVenous blood was taken after a requested minimum five hour fast before participants had a standard 75 g two hour oral glucose tolerance test at study phases 3, 5, 7, and 9. Glucose samples were drawn into fluoride monovette tubes and centrifuged on site within one hour. Blood glucose was measured by using the glucose oxidase method, as previously described.34 At each phase, diabetes was defined by WHO criteria based on fasting glucose =7.0 mmol/L or two hour glucose =11.1 mmol/L.35 Participants reporting diabetes diagnosed by a doctor or use of antidiabetic drugs were classified as having diabetes regardless of their oral glucose tolerance test results. The date of diagnosis of diabetes was assigned according to the interval method as the midpoint between the first visit with a diagnosis of diabetes and the last visit without diabetes.34

Statistical analysisWe applied multivariate imputation based on sex, age, ethnicity, socioeconomic status, health behaviours, body mass index, and biological markers at the preceding phase to impute missing values on health behaviours, body mass index, or biological risk markers at phases 3, 5, and 7. Twenty per cent of the participants had at least one value imputed at one of the follow-ups.

As no differences related to sex or ethnicity were apparent in the association between socioeconomic status and incidence of type 2 diabetes (hazard ratio 1.85, 95% confidence interval 1.45 to 2.45, among men and 1.71, 1.16 to 2.43, among women, P for interaction=0.80; 1.89, 1.49 to 2.41, among white people and 1.59, 0.85 to 2.95, among non-white people, P for interaction=0.98), we pooled data for the two sexes and the two ethnic groups and adjusted analyses for sex and ethnicity. We used Cox regression to examine the association of socioeconomic status, health behaviours, body mass index, and biological risk markers with incident diabetes. As tests did not suggest departure from a linear trend (P for departure from a linear trend=0.20), we used socioeconomic status as a continuous three level variable. Sensitivity analysis using socioeconomic status as a categorical variable yielded similar results (supplementary table G). We squared the hazard ratio associated with a unit change in socioeconomic status to yield the hazard ratio for lowest versus highest category of socioeconomic status.

We firstly adjusted Cox regression models for age, sex, ethnicity, and family history of diabetes (model 1 or reference model 1). We then entered health behaviours and body mass index first individually and then simultaneously into model 1. Model 2 included adjustment for all health behaviours, and model 3 (or reference model 2 for further model comparisons) included adjustment for all health behaviours and body mass index. Subsequently, we entered the biological markers individually into model 3, and we finally entered all risk factors/markers simultaneously into a full multivariable model (model 4).

We determined the contribution of each risk factor/marker in explaining the association between socioeconomic status and type 2 diabetes by calculating the percentage attenuation in the ß coefficient for socioeconomic status after inclusion of the risk factor in question in the reference model: “100×(ßref model-ßref model+risk factor(s))/(ßref model)”. We calculated a 95% confidence interval around the percentage attenuation by using a bootstrap method with 1000 re-samplings. We repeated the analyses for the role of risk factors/markers in the association between socioeconomic status and type 2 diabetes three times using different assessments. Firstly, we entered risk factors/markers as assessed at the baseline of the study (phase 3). Secondly, we assessed them longitudinally over the follow-up (phases 3, 5, and 7) and entered them in the Cox regressions as time dependent variables. Thirdly, we extended this model to assess long term exposure to the risk factors/markers. We assessed this by adjusting, at each follow-up period, for the risk factors/markers at the current phase plus at the previous phase (two phases capturing an exposure period of approximately five years). Thus, for the follow-up period between phases 3 and 5, we entered risk factors/markers assessed at phase 3 into the model together with the risk factors/markers assessed at phase 1. For the follow-up period between phases 5 and 7, were entered risk factors/markers collected at phases 3 and 5 simultaneously, and for the follow-up period between phases 7 and 9, we entered risk factors/markers from phases 5 and 7 together. We tested the proportional hazard assumptions for Cox regression models by using Schoenfeld residuals and found them not to be violated (all P values =0.05). We used the statistical software Stata 11.1 and SAS 9.2 (%BOOT and %BOOTCI macros) for analyses.

ResultsOf the 8815 participants who took part in the phase 3 examination (that is, the baseline of the analyses reported here), we excluded 1578 for one or more of the following reasons: prevalent type 2 diabetes at phase 3 (n=162), missing follow-up on type 2 diabetes status (n=588), and missing data on risk factors/markers at phase 1 (n=1392). The final sample consisted of 7237 participants (2196 women). Excluded participants were more likely to belong to the low socioeconomic status group and were slightly older than those included in the analyses (P<0.001).

Table 1? shows baseline characteristics of the participants included in the analysis. During the mean 14.2 years follow-up, 818 incident cases type 2 diabetes were identified on the basis of a 75 g oral glucose tolerance test (n=425; 52%), use of antidiabetic drugs (n=188; 23%), or diagnosis by a physician (n=205; 25%). Participants in the lowest socioeconomic category had an almost twofold higher incidence of type 2 diabetes than those in the highest category (10.9 v 5.6 per 1000 person years). The prevalences of smoking, unhealthy diet, physical inactivity, obesity, high triglyceride concentration, and low high density lipoprotein cholesterol were higher in the lowest compared with the highest socioeconomic group (P<0.001), whereas heavy drinking was more common in the highest socioeconomic group (P<0.001). Socioeconomic status was unrelated to high blood pressure (P=0.72).

View this table:View PopupView InlineTable 1 Study participants’ characteristics at phase 3 (baseline) and incidence of diabetes over 17.7 years of follow-up by socioeconomic status. Values are numbers (percentages) unless stated otherwise

Table 2? shows results for the association between risk factors/markers for diabetes and incidence of type 2 diabetes. Unhealthy behaviours were related to an increased risk of developing type 2 diabetes over the follow-up. As anticipated, the associations of overweight (hazard ratio 1.92, 95% confidence interval 1.64 to 2.25) and obesity (4.79, 3.96 to 5.80) with incidence of type 2 diabetes were particularly strong. Hypertension and adverse lipid categories were also associated with type 2 diabetes, as was family history of diabetes.

View this table:View PopupView InlineTable 2 Association of health behaviours and other risk factors assessed at baseline (phase 3) with type 2 diabetes incidence (n=7237)

Table 3? shows results for the association between socioeconomic status and incidence of type 2 diabetes, as well as the contribution of health behaviours, body mass index, and biological risk markers assessed at phase 3 to this association. The hazard ratio for the lowest versus the highest socioeconomic status was 1.86 (1.48 to 2.32). This was attenuated by 17% when we controlled for health behaviours at baseline and by 18% when we controlled for body mass index. Overall, health behaviours and body mass index attenuated the association between socioeconomic status and type 2 diabetes by 33% (-1% to 78%). Adjustment for baseline biological risk markers (entered as continuous variables in the model) lowered the association by an additional 12%. In total, 45% (17% to 105%) of the socioeconomic gradient in type 2 diabetes was explained.

View this table:View PopupView InlineTable 3 Contribution of baseline risk factors/markers (phase 3) in explaining social inequalities in type 2 diabetes incidence (n=7237)

In table 4? shows the results when the risk factors/markers were assessed repeatedly over the follow-up. The first column shows that with longitudinal assessment over the follow-up, health behaviours and body mass index in combination explained 36% (22% to 64%) of the association between socioeconomic status and type 2 diabetes. This proportion increased to 45% (28% to 77%) when we additionally took blood lipids and systolic blood pressure into account. The right side of table 4? shows results of simultaneous adjustment for long term exposure to the risk factors/markers and their changes over time. In this model, health behaviours attenuated the socioeconomic status coefficient by 24% and body mass index alone by 23%; the total percentage attenuation due to health behaviours and body mass index was 45% (28% to 75%). Blood lipids and blood pressure contributed to an additional 8%, and in the final fully adjusted model 53% (29% to 88%) of the association between socioeconomic status and type 2 diabetes was explained.

View this table:View PopupView InlineTable 4 Contribution of repeatedly measured risk factors/markers in explaining social inequalities in type 2 diabetes incidence (n=7237)

Sensitivity analysesWe repeated all analyses in subgroups including only participants with complete data, only those who were free from coronary heart disease at baseline, and only white participants, as well as including adjustment for waist circumference and body mass index assessed at age 25. These yielded similar results to those reported in the main analysis (results available on request).

We repeated all analyses for men and women separately (supplementary tables A to D). Although results did not materially differ between the sexes, modifiable risk factors tended to explain a larger proportion of the socioeconomic gradient in type 2 diabetes in women than in men (attenuation for the model accounting for long term exposure to the risk factors: 42% in men and 81% in women, P for difference between the two estimations=0.43).

To examine whether our results are robust across different indicators of socioeconomic status, we repeated all analyses using education and income as alternative measures. Our findings of a major contribution of modifiable risk factors to socioeconomic differences in type 2 diabetes were consistent across the indicators of socioeconomic status (supplementary tables E and F). We also repeated the analysis using employment grade in six categories (supplementary table G). Again, the results were very similar to those in the main analysis based on employment grade in three categories.

Finally, we used three standard approaches to examine whether missing data on risk factors at baseline affected the findings. Firstly, we repeated the analysis using only three of the risk factors examined: smoking, alcohol consumption, and body mass index. These risk factors were available on a larger sample of the population (n=7750), allowing us to assess whether their role in explaining socioeconomic differences in type 2 diabetes in this larger sample was similar to that found in the smaller sample included in the main analysis. Regarding the model with baseline assessment of these risk factors, the contribution of smoking was 10% in the larger sample compared with 9% in the smaller sample. The contribution of alcohol consumption was 3% versus 3%, and that of body mass index was 20% versus 18%. Secondly, we used “inverse probability weighting” to correct the estimates for non-response.36 These analyses yielded similar results to those reported in the main analysis (supplementary table H). Thirdly, we used multiple multivariate imputation to replace missing values for risk factors at the study baseline (Stata ice/micombine procedures). Analyses on the imputed dataset (n=8232; 927 incident diabetes cases) yielded results virtually identical to those reported in the main analysis (results available on request).

DiscussionThis study aimed to quantify the contribution of health behaviours, body mass index, and biological risk markers to the association between socioeconomic status and the incidence of type 2 diabetes in a population of British civil servants followed up for a mean of 14.2 years. We found that health behaviours and body mass index explained 33% of socioeconomic differences in incidence of diabetes when they were assessed at study baseline, 36% when assessed repeatedly over the follow-up, and 45% when we additionally accounted for long term exposure. In these three assessments, body mass index was the most important single contributing factor. After we additionally took account of adverse lipid profile and systolic blood pressure, up to 53% of the association between socioeconomic status and type 2 diabetes was explained.

Strengths and weaknessesThis study has two major strengths. Firstly, it is to our knowledge the first to assess the effect of health behaviours and body mass index on socioeconomic differences in type 2 diabetes by using different assessments of current and long term exposure to these factors over the follow-up. This allowed us to examine the possibility that changes in these factors over the study period or a long term exposure might have yielded different results. Secondly, unlike previous studies, we provide a confidence interval around the percentage attenuation of the association between socioeconomic status and type 2 diabetes after inclusion of the risk factors examined. Adding a degree of precision to the estimates of the contribution of risk factors to social inequalities greatly helps with the interpretation of these findings.

This study also has some limitations. As the findings were from an occupational cohort, they may not fully apply to the general population, which also includes people not in paid employment. Despite a high response to the survey at the successive data collection phases, loss to follow-up accumulated over the extended time period, as is inevitable in long term prospective studies. We used an imputation procedure to replace missing values for the risk factors considered. Our sensitivity analyses showed that results from analyses using complete case data differed little from those using imputed data.

Comparison with previous studiesIn our study, participants in the lowest occupational group had a 1.86-fold greater risk of developing type 2 diabetes over the follow-up compared with those in the highest occupational group. This is slightly higher than the 1.31-fold increased risk of incident type 2 diabetes in the lowest category of socioeconomic status found in the most recent meta-analysis of cohort studies in high income countries.11 Health behaviours and body mass index explained about a third of socioeconomic differences in incidence of type 2 diabetes when assessed at baseline—this is consistent with previous reports on this and other cohorts10 21 22—but up to 45% when we accounted simultaneously for changes over time and long term exposure. The difference in contributions of risk factors when measured once compared with repeatedly was mainly due to an increased explanatory power of physical activity (from 1% to 10%) and body mass index (from 18% to 23%). Long term exposure to these risk factors may be captured better when it is assessed at multiple points in time rather than on just one occasion. Moreover, adjustment for the long term effect of body mass index may be important, as duration of exposure to obesity has been linked to increased risk of type 2 diabetes.37

Recent studies have suggested that social inequalities in type 2 diabetes might be larger in women than in men,38 39 whereas in our study the socioeconomic gradient in incidence of type 2 diabetes did not differ by sex. Our data came from an occupational cohort, which may result in the characteristics for men and women being more homogeneous than in the general population. Moreover, most studies reporting sex differences in the social patterning of type 2 diabetes were based on prevalence data,38 39 whereas our study examined incidence. However, in our study the modifiable risk factors examined tended to explain a larger proportion of the association between socioeconomic status and type 2 diabetes in women than in men, because of sex differences in the social patterning of these risk factors.

In contrast to our previously published paper on socioeconomic differences in mortality,23 the contribution of health behaviours to social inequalities in incidence of type 2 diabetes did not increase substantially when we used repeated assessments of the behaviours during the follow-up rather than using only one assessment at baseline. The effect of changes in unhealthy behaviours may be more pronounced on determinants of mortality than for type 2 diabetes. Alternatively, reverse causation could partly explain the larger proportion of socioeconomic differences explained with repeated versus baseline only assessment when the outcome is mortality instead of morbidity.40 In mortality analyses, changes in unhealthy behaviours may be elicited by non-fatal chronic diseases preceding death.

Meaning and implications of studyOf the modifiable risk factors examined, body mass index contributed the most and alone explained about 20% of socioeconomic differences. The major role of excess weight in the onset of type 2 diabetes is well established.41 As weight gain is strongly socially patterned, the finding that obesity also plays a major role in shaping social inequalities in type 2 diabetes is not surprising. In contrast, with only 8% and 1% attenuation of the association between socioeconomic status and type 2 diabetes (8% and 10% when we assessed long term exposure), the effects of diet and physical activity were smaller than one would expect given that these behaviours were also strongly socially patterned. We might have underestimated their effect relative to that of body mass index because this is measured with greater precision than questionnaire based diet and physical activity assessment.42 43

Although smoking was associated with incidence of type 2 diabetes and was strongly socially patterned, its contribution to socioeconomic differences in type 2 diabetes was modest. The role of alcohol consumption was also negligible. This is probably because participants in the highest category of socioeconomic status were more likely to be heavy drinkers than were those in the lowest category, a finding also observed in other occupational cohorts.44 We found that dyslipidaemia (high triglycerides in particular) explained an additional 10% of socioeconomic differences in incidence of type 2 diabetes. In contrast, the contribution of hypertension was almost null, consistent with equal distribution of elevated blood pressure across socioeconomic groups and the lack of socioeconomic inequalities in prescription of antihypertensive drugs in the United Kingdom.45 The treatment of high triglycerides and low high density lipoprotein cholesterol is not a primary aim in clinical practice; these biomarkers are unlikely to affect the social patterning of diabetes.46

The fact that unhealthy behaviours and body mass index explained up to 45% of the socioeconomic gradient in type 2 diabetes in this population in early old age has important public health implications. Type 2 diabetes can be delayed or prevented among people at high risk who make intensive lifestyle modifications.47 48 Further efforts should be made to promote and enable the adoption of healthy lifestyles among the disadvantaged fractions of society. Targeting diabetogenic lipid profiles might additionally be considered,49 as in our study dyslipidaemia (high triglycerides in particular) explained an additional 10% of socioeconomic differences in incidence of type 2 diabetes. However, the extent to which altered concentrations of triglycerides are a consequence of increased adiposity or insulin resistance or are an independent risk factor for the development of type 2 diabetes remains unclear.50 51 Moreover, clinical implications should take into account the fact that drugs that directly target triglycerides and high density lipoprotein cholesterol are associated with a slight increase in blood glucose concentrations, an unwanted side effect for people at high risk of diabetes,52 and are less effective than expected.53

Unanswered questionsSimilarly to previous findings on cardiovascular diseases in this cohort,54 55 about 50% of the socioeconomic gradient in type 2 diabetes remained unexplained after we had accounted for all major risk factors for the disease. Other potential mediators of the association between socioeconomic status and type 2 diabetes in adults are psychosocial factors and psychological states, such as chronic stressors and depression,13 56 exposure to adverse socioeconomic circumstances in utero or during childhood,57 or inadequate access to healthcare.13 However, studies that have assessed the contribution of psychosocial factors have found no evidence for an effect on social inequalities in diabetes,10 21 and medical care seems to contribute more to social inequalities in management of diabetes than to its onset.13 Although evidence suggests that exposure to adverse socioeconomic circumstances in early life or depression might play a role in social inequalities in type 2 diabetes,56 58 to our knowledge no study so far has investigated this question. Further investigations based on longitudinally assessed risk factors are therefore needed. Finally, as noted above, the extent to which unhealthy diet and low physical activity would contribute to the socioeconomic gradient in type 2 diabetes remains unknown until these risk factors are assessed with greater precision at the population level—for example, with objective measures.

ConclusionsHealth behaviours and body mass index explain almost half of the association between socioeconomic status and incidence of type 2 diabetes. Adverse blood lipids, which might be an intervention target for prevention of diabetes in the future, also contributed to social inequalities associated with type 2 diabetes. Given the increasing burden of type 2 diabetes and the observed increase in social inequalities in prevalence of type 2 diabetes,52 further efforts to tackle these factors are urgently needed.

What is already known on this topicThe burden of type 2 diabetes disproportionally affects the lower socioeconomic groups, but the reasons for its uneven distribution remain unclear

Lifestyle related risk factors are potentially important mediators of the association between socioeconomic status and type 2 diabetes

Previous studies have offered only a one-off measurement of these factors and have potentially underestimated their effect on social inequalities in incidence of type 2 diabetes

What this study addsHealth behaviours and body mass index, when assessed repeatedly over time, explained almost half of the association between socioeconomic status and incidence of type 2 diabetes

Adverse blood lipids, which might be an intervention target for prevention of diabetes in the future, also contributed to explaining the social inequalities in incident type 2 diabetes

NotesCite this as: BMJ 2012;345:e5452

FootnotesWe thank all of the participating civil service departments and their welfare, personnel, and establishment officers; the British Occupational Health and Safety Agency; the British Council of Civil Service Unions; all participating civil servants in the Whitehall II study; and all members of the Whitehall II Study Team. The Whitehall II Study Team comprises research scientists, statisticians, study coordinators, nurses, data managers, administrative assistants, and data entry staff, who make the study possible.

Contributors: SStringhini analysed the data and wrote the first and successive drafts of the paper. MK conceived the study. MK, AT, MS, and SSabia contributed to data analysis. All authors contributed to the interpretation of results and to the writing of the paper, critically revised each version of the manuscript, and approved the final version of the paper. S Stringhini is the guarantor.

Funding: SStringhini is supported by a postdoctoral fellowship awarded by the Swiss School of Public Health. MK is supported by the UK Medical Research Council (MRC), the US National Institutes of Health (NIH) (R01HL036310; R01AG034454), the EU New OSH ERA Research Programme, and an Economic and Social Research Council (ESRC) professorship. DB is a Wellcome Trust fellow. TA is supported by the National Heart, Lung, and Blood Institute (R01HL036310). SSabia is supported by a grant from the National Institute of Aging, NIH (R01AG034454). MS is supported by the British Heart Foundation. The Whitehall II study has been supported by grants from the MRC; the British Heart Foundation; the British Health and Safety Executive; the British Department of Health; the National Heart, Lung, and Blood Institute (R01HL036310); and the National Institute on Aging, NIH. The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology is funded as part of the joint UK research council call for lifelong health and wellbeing. The funding organisations or sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Ethical approval: This study was approved by the University College London ethics committee, and all participants provided written consent.

Data sharing: Whitehall II data are available to the scientific community. Please refer to the Whitehall II data sharing policy at www.ucl.ac.uk/whitehallII/data-sharing.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

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