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.

Figure 1. Association of lifecourse socioeconomic status with two inflammatory markers and type 2 diabetes.

Lower SES is associated with higher CRP (A) and IL-6 levels (B) and with a greater type 2 diabetes risk (C) after adjustment for sex, age, and ethnicity. All p for linear trend between lifecourse SES and inflammatory markers or type 2 diabetes were <0.001. Cumulative SES score includes father's occupational position, participants' education, and participants' occupational position at phase 3. Each SES measure was a 3-level variable with values ranging from 0 (high) to 2 (low). A score was calculated by summing each SES measure (range 0–6). The final cumulative SES score was categorized as high (score = 0–2), middle (score = 3–5), and low (score = 6). Lifecourse SES trajectory refers to father's occupational position and participants' occupational position at phase 3. p-y, person-years; T2D, type 2 diabetes.

Figure 2. Contribution of smoking, physical activity, diet, BMI, CRP, and IL-6 to the association between lifecourse socioeconomic status and type 2 diabetes incidence.

The first bar shows explanatory factors for the associations of low cumulative SES score (ref. high cumulative SES score) (A) and adverse SES-trajectory (ref. high-high SES trajectory) (B) with type 2 diabetes (T2D). Inflammatory markers, in combination, explain 26% (95% CI 16%–46%) of the first association (A) and 34% (95% CI 20%–62%) of the latter association (B). All associations are adjusted for age, sex, ethnicity, family history of T2D, and prevalent conditions. Cumulative SES score includes father's occupational position, participants' education, and participants' occupational position at phase 3. Each SES measure was a 3-level variable with values ranging from 0 (high) to 2 (low). A score was calculated by summing each SES measure (range 0–6). The final cumulative SES score was categorized as high (score = 0–2), middle (score = 3–5), and low (score = 6). Lifecourse SES trajectory refers to father's occupational position and participants' occupational position at phase 3.

Figure 3. Simplified conceptual framework for the potential role of inflammatory processes in explaining social inequalities in type 2 diabetes.

Socioeconomic adversity over the lifetime is hypothesized to be associated with type 2 diabetes risk. Part of this association might be mediated by the elevated inflammatory states resulting from altered gene expression and/or unhealthy lifestyles, both related to socioeconomic adversity. Other factors (e.g., low birth weight) may also mediate part of the association between SES and type 2 diabetes (arrow A). Furthermore, SES is hypothesized to contribute to elevated inflammation because of comorbid conditions (arrow B).