Stress increases the risk of type 2 diabetes onset in women: A 12-year longitudinal study using causal modelling

<div><p>Background</p><p>Type 2 diabetes is associated with significant morbidity and mortality. Modifiable risk factors have been found to contribute up to 60% of type 2 diabetes risk. However, type 2 diabetes continues to rise despite implementation of interventions based on traditional risk factors. There is a clear need to identify additional risk factors for chronic disease prevention. The aim of this study was to examine the relationship between perceived stress and type 2 diabetes onset, and partition the estimates into direct and indirect effects.</p><p>Methods and findings</p><p>Women born in 1946–1951 (n = 12,844) completed surveys for the Australian Longitudinal Study on Women’s Health in 1998, 2001, 2004, 2007 and 2010. The total causal effect was estimated using logistic regression and marginal structural modelling. Controlled direct effects were estimated through conditioning in the regression model. A graded association was found between perceived stress and all mediators in the multivariate time lag analyses. A significant association was found between hypertension, as well as physical activity and body mass index, and diabetes, but not smoking or diet quality. Moderate/high stress levels were associated with a 2.3-fold increase in the odds of diabetes three years later, for the total estimated effect. Results were only slightly attenuated when the direct and indirect effects of perceived stress on diabetes were partitioned, with the mediators only explaining 10–20% of the excess variation in diabetes.</p><p>Conclusions</p><p>Perceived stress is a strong risk factor for type 2 diabetes. The majority of the effect estimate of stress on diabetes risk is not mediated by the traditional risk factors of hypertension, physical activity, smoking, diet quality, and body mass index. This gives a new pathway for diabetes prevention trials and clinical practice.</p></div

Comparison of sociodemographic characteristics between women with incident type 2 diabetes compared with women without a diagnosis of type 2 diabetes over the observation period.

<p>Comparison of sociodemographic characteristics between women with incident type 2 diabetes compared with women without a diagnosis of type 2 diabetes over the observation period.</p

Longitudinal associations between the hypothesised mediators and type 2 diabetes, using a time lag approach.

<p>Each analysis is adjusted for the potential confounders of SES (measured by educational attainment) and age, as well as secular trends (time by survey). The aim here is to identify the relationship between each mediator and the outcome of type 2 diabetes. The combined effect of all the mediators is modelled in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172126#pone.0172126.t004" target="_blank">Table 4</a>.</p

Longitudinal associations between perceived stress and hypothesised mediators using a time lag approach.

<p>Each analysis is adjusted for the potential confounders of SES (measured by educational attainment) and age, as well as secular trends (time by survey).</p

Total causal effects of perceived stress on type 2 diabetes using a time lag approach (assuming physical activity as a time varying mediator).^a^,^b

<p>Total causal effects of perceived stress on type 2 diabetes using a time lag approach (assuming physical activity as a time varying mediator).<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172126#t004fn001" target="_blank">^a</a>^,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172126#t004fn002" target="_blank">^b</a></p

Simplified Directed Acyclic Graph showing hypothesised causal mechanism between perceived stress and type 2 diabetes taking into account potential confounders and mediators.

<p>According to the DAG, perceived stress (measured at Survey 2) may be mediated through physical activity, diet quality (or BMI instead of diet), hypertension and smoking status and confounded by age and socioeconomic status (i.e. highest educational qualification).</p