Dataset Information

Association of lifecourse socioeconomic status with chronic inflammation and type 2 diabetes risk: the Whitehall II prospective cohort study.

ABSTRACT:

Background

Socioeconomic adversity in early life has been hypothesized to "program" a vulnerable phenotype with exaggerated inflammatory responses, so increasing the risk of developing type 2 diabetes in adulthood. The aim of this study is to test this hypothesis by assessing the extent to which the association between lifecourse socioeconomic status and type 2 diabetes incidence is explained by chronic inflammation.

Methods and findings

We use data from the British Whitehall II study, a prospective occupational cohort of adults established in 1985. The inflammatory markers C-reactive protein and interleukin-6 were measured repeatedly and type 2 diabetes incidence (new cases) was monitored over an 18-year follow-up (from 1991-1993 until 2007-2009). Our analytical sample consisted of 6,387 non-diabetic participants (1,818 women), of whom 731 (207 women) developed type 2 diabetes over the follow-up. Cumulative exposure to low socioeconomic status from childhood to middle age was associated with an increased risk of developing type 2 diabetes in adulthood (hazard ratio [HR]?=?1.96, 95% confidence interval: 1.48-2.58 for low cumulative lifecourse socioeconomic score and HR?=?1.55, 95% confidence interval: 1.26-1.91 for low-low socioeconomic trajectory). 25% of the excess risk associated with cumulative socioeconomic adversity across the lifecourse and 32% of the excess risk associated with low-low socioeconomic trajectory was attributable to chronically elevated inflammation (95% confidence intervals 16%-58%).

Conclusions

In the present study, chronic inflammation explained a substantial part of the association between lifecourse socioeconomic disadvantage and type 2 diabetes. Further studies should be performed to confirm these findings in population-based samples, as the Whitehall II cohort is not representative of the general population, and to examine the extent to which social inequalities attributable to chronic inflammation are reversible.

SUBMITTER: Stringhini S

PROVIDER: S-EPMC3699448 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Association of lifecourse socioeconomic status with chronic inflammation and type 2 diabetes risk: the Whitehall II prospective cohort study.

Stringhini Silvia S Batty G David GD Bovet Pascal P Shipley Martin J MJ Marmot Michael G MG Kumari Meena M Tabak Adam G AG Kivimäki Mika M

PLoS medicine 20130702 7

<h4>Background</h4>Socioeconomic adversity in early life has been hypothesized to "program" a vulnerable phenotype with exaggerated inflammatory responses, so increasing the risk of developing type 2 diabetes in adulthood. The aim of this study is to test this hypothesis by assessing the extent to which the association between lifecourse socioeconomic status and type 2 diabetes incidence is explained by chronic inflammation.<h4>Methods and findings</h4>We use data from the British Whitehall II s ...[more]

PMID: 23843750

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Project description:Background & aimsLow-grade inflammation appears to play an etiological role in cognitive decline. However the association between an inflammatory dietary pattern and cognitive decline has not been investigated. We aimed to investigate dietary patterns associated with inflammation and whether such diet is associated with cognitive decline.MethodsWe analyzed 5083 participants (28.7% women) from the Whitehall II cohort study. Diet and serum interleukin-6 (IL-6) were assessed in 1991-1993 and 1997-1999. We used reduced rank regression methods to determine a dietary pattern associated with elevated IL-6. Cognitive tests were performed in 1997-1999 and repeated in 2002-2004 and 2007-2009. The association between dietary pattern and cognitive decline between ages 45 and 79 was assessed using linear mixed models.ResultsWe identified an inflammatory dietary pattern characterized by higher intake of red meat, processed meat, peas and legumes, and fried food, and lower intake of whole grains which correlated with elevated IL-6 both in 1991-1993 and 1997-1999. A greater decline in reasoning was seen in participants in the highest tertile of adherence to the inflammatory dietary pattern (-0.37 SD; 95% confidence interval [CI] -0.40, -0.34) compared to those in the lowest tertile (-0.31; 95% CI -0.34, -0.28) after adjustment for age, sex, ethnicity, occupational status, education, and total energy intake (p for interaction across tertiles = 0.01). This association remained significant after multivariable adjustment. Similarly for global cognition, the inflammatory dietary pattern was associated with faster cognitive decline after multivariable adjustment (p for interaction across tertiles = 0.04). Associations were stronger in younger participants (<56 years), reducing the possibility of reverse causation.ConclusionsOur study found that a dietary pattern characterized as higher intake of red and processed meat, peas, legumes and fried food, and lower intake of whole grains was associated with higher inflammatory markers and accelerated cognitive decline at older ages. This supports the case for further research.

Project description:BackgroundDifferences in morbidity and mortality between socioeconomic groups constitute one of the most consistent findings of epidemiologic research. However, research on social inequalities in health has yet to provide a comprehensive understanding of the mechanisms underlying this association. In recent analysis, we showed health behaviours, assessed longitudinally over the follow-up, to explain a major proportion of the association of socioeconomic status (SES) with mortality in the British Whitehall II study. However, whether health behaviours are equally important mediators of the SES-mortality association in different cultural settings remains unknown. In the present paper, we examine this issue in Whitehall II and another prospective European cohort, the French GAZEL study.Methods and findingsWe included 9,771 participants from the Whitehall II study and 17,760 from the GAZEL study. Over the follow-up (mean 19.5 y in Whitehall II and 16.5 y in GAZEL), health behaviours (smoking, alcohol consumption, diet, and physical activity), were assessed longitudinally. Occupation (in the main analysis), education, and income (supplementary analysis) were the markers of SES. The socioeconomic gradient in smoking was greater (p<0.001) in Whitehall II (odds ratio [OR] = 3.68, 95% confidence interval [CI] 3.11-4.36) than in GAZEL (OR = 1.33, 95% CI 1.18-1.49); this was also true for unhealthy diet (OR = 7.42, 95% CI 5.19-10.60 in Whitehall II and OR = 1.31, 95% CI 1.15-1.49 in GAZEL, p<0.001). Socioeconomic differences in mortality were similar in the two cohorts, a hazard ratio of 1.62 (95% CI 1.28-2.05) in Whitehall II and 1.94 in GAZEL (95% CI 1.58-2.39) for lowest versus highest occupational position. Health behaviours attenuated the association of SES with mortality by 75% (95% CI 44%-149%) in Whitehall II but only by 19% (95% CI 13%-29%) in GAZEL. Analysis using education and income yielded similar results.ConclusionsHealth behaviours were strong predictors of mortality in both cohorts but their association with SES was remarkably different. Thus, health behaviours are likely to be major contributors of socioeconomic differences in health only in contexts with a marked social characterisation of health behaviours. Please see later in the article for the Editors' Summary.

Project description:ObjectiveTo 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.DesignProspective 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.SettingCivil service departments in London (Whitehall II study).Participants7237 adults without diabetes (mean age 49.4 years; 2196 women).Main outcome measuresIncidence of type 2 diabetes and contribution of risk factors to its association with socioeconomic status.ResultsOver 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).ConclusionsModifiable 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.

Project description:ObjectivesTo assess the performance of a panel of common single nucleotide polymorphisms (genotypes) associated with type 2 diabetes in distinguishing incident cases of future type 2 diabetes (discrimination), and to examine the effect of adding genetic information to previously validated non-genetic (phenotype based) models developed to estimate the absolute risk of type 2 diabetes.DesignWorkplace based prospective cohort study with three 5 yearly medical screenings.Participants5535 initially healthy people (mean age 49 years; 33% women), of whom 302 developed new onset type 2 diabetes over 10 years.Outcome measuresNon-genetic variables included in two established risk models-the Cambridge type 2 diabetes risk score (age, sex, drug treatment, family history of type 2 diabetes, body mass index, smoking status) and the Framingham offspring study type 2 diabetes risk score (age, sex, parental history of type 2 diabetes, body mass index, high density lipoprotein cholesterol, triglycerides, fasting glucose)-and 20 single nucleotide polymorphisms associated with susceptibility to type 2 diabetes. Cases of incident type 2 diabetes were defined on the basis of a standard oral glucose tolerance test, self report of a doctor's diagnosis, or the use of anti-diabetic drugs.ResultsA genetic score based on the number of risk alleles carried (range 0-40; area under receiver operating characteristics curve 0.54, 95% confidence interval 0.50 to 0.58) and a genetic risk function in which carriage of risk alleles was weighted according to the summary odds ratios of their effect from meta-analyses of genetic studies (area under receiver operating characteristics curve 0.55, 0.51 to 0.59) did not effectively discriminate cases of diabetes. The Cambridge risk score (area under curve 0.72, 0.69 to 0.76) and the Framingham offspring risk score (area under curve 0.78, 0.75 to 0.82) led to better discrimination of cases than did genotype based tests. Adding genetic information to phenotype based risk models did not improve discrimination and provided only a small improvement in model calibration and a modest net reclassification improvement of about 5% when added to the Cambridge risk score but not when added to the Framingham offspring risk score.ConclusionThe phenotype based risk models provided greater discrimination for type 2 diabetes than did models based on 20 common independently inherited diabetes risk alleles. The addition of genotypes to phenotype based risk models produced only minimal improvement in accuracy of risk estimation assessed by recalibration and, at best, a minor net reclassification improvement. The major translational application of the currently known common, small effect genetic variants influencing susceptibility to type 2 diabetes is likely to come from the insight they provide on causes of disease and potential therapeutic targets.

Dataset Information

Association of lifecourse socioeconomic status with chronic inflammation and type 2 diabetes risk: the Whitehall II prospective cohort study.

Background

Methods and findings

Conclusions

Publications

Association of lifecourse socioeconomic status with chronic inflammation and type 2 diabetes risk: the Whitehall II prospective cohort study.

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