Executive functioning and diabetes: The role of anxious arousal and inflammation
Introduction
Emotional stress is a risk factor for poor physical health. Indeed, high anxiety is associated with diabetes incidence (Li et al., 2008). A better understanding of the association between anxiety and blood glucose is important given that approximately 347 million people worldwide have diabetes, which has imposed a growing economic strain on health care systems (Zhang et al., 2010). Moreover, approximately 90% of all diabetes is type 2, which can be prevented or delayed via lifestyle changes (e.g., physical activity, diet; Tuomilehto and Wolf, 1987, WHO, 2014) that are more difficult to achieve when stressed or anxious (Stults-Kolehmainen and Sinha, 2014). Therefore, a further understanding of the association between anxiety and blood glucose is needed to improve interventions. The present study draws from the psychoneuroimmunology literature to examine how cognitive processes and immune functioning underlie the association between anxious arousal and glycated hemoglobin (HbA1c), a well-known biomarker used to estimate blood glucose during the preceding 2–3 months.
The executive function of inhibition (also known as attentional control or inhibitory control) is associated with the experience of stressful emotions such as anxiety. Inhibition is the ability to refrain from responding or attending to tempting/distracting information, objects, thoughts, or activities. Indeed, those who have low inhibition are more likely to attend to anxious thoughts, and have greater difficulty shifting their attention away from such thoughts, than those with high inhibition (DeGutis et al., 2015, Joormann and Gotlib, 2010, Schmeichel and Tang, 2015). Others have argued that better inhibition is associated with less anxiety via the ability to flexibly and adaptively respond to one’s environment using optimal coping strategies (e.g., Martel et al., 2007). Indeed, inflexibility in thinking is associated with increased anxiety (e.g., Britton et al., 2010), which may explain why those with better inhibition report less anxiety than those with poor inhibition. The neurovisceral integration model (e.g., Thayer and Lane, 2009) also indicates that those with poor inhibition are less physiologically capable of responding and adapting to their environment in comparison to those with better inhibition. As a result, those with poor inhibition are more likely to have a pre-attentive bias to threat information than those with better inhibition due to an inability to flexibly respond, and are more likely to report increased arousal due to this bias (Thayer and Friedman, 2004). Therefore, both cognitive and physiological processes may link poor inhibition with increased anxiety. High anxiety is associated with poor overall physical health in adults (Needham et al., 2015), which is notable given that those with low inhibition as children exhibit poor physical health outcomes in adulthood (Moffitt et al., 2011).
The underlying mechanisms linking low inhibition and poor health have not been adequately studied. In addition to increased anxiety (Schmeichel and Tang, 2015), low inhibition is also a risk factor for poor diabetes management because of an inability to consistently adhere to and complete diabetes management tasks (Wasserman et al., 2015). Therefore, it is important to generate a further understanding of how inhibition is linked to diabetes to improve prevention and intervention efforts.
Inflammation may play an important role in linking inhibition and diabetes. Those with high stress demonstrate a greater inflammatory response than individuals who are less stressed at the moderate effect size level (i.e., r = 0.42 to 0.57; Fagundes et al., 2013). Anxiety, as well as stress more generally, leads to inflammation via activation of nuclear factor-kappa B (NF-KB). Activation of NF-KB increases production of pro-inflammatory cytokines such as interleukin-6 (Bierhaus et al., 2003). Further, chronic inflammation is a reliable predictor of diabetes onset at the small effect size level (i.e., r = 0.28–0.33; Chen et al., 2009, Perticone et al., 2008, Weng et al., 2010), as well as morbidity and mortality with small to moderate effect sizes typically identified (i.e., r = 0.10–0.40; Kiecolt-Glaser et al., 2010). In addition to inflammation being a predictor of diabetes onset, diabetes progression is associated with increased inflammation over time (Stehouwer et al., 2002). Chronic elevated inflammation is associated with increased risk of heart disease (OR = 1.45; Hansson, 2005), a major complication of diabetes (Grundy et al., 1999). Indicators of anxious arousal (e.g., racing heart, chest pain) are stronger predictors of inflammation than cognitive anxiety (e.g., fearful of dying or losing control) at the small effects size level (r = 0.12; Duivis et al., 2013), possibly due to activation of the sympathetic nervous system (Janig, 2014).
As low inhibition is associated with high anxious arousal at the medium effect size level (r = 0.38; DeGutis et al., 2015), low inhibition may also be associated with high inflammation; however, it is unclear if inhibition is associated with inflammation in the general population as the literature has primarily been focused on the natural decline of cognitive skills and increase in inflammation near the end of human life (Magaki et al., 2007, Simen et al., 2011). Furthermore, inhibition is typically combined with other cognitive abilities in statistical analyses, limiting the ability to understand the unique effects of inhibition (Marsland et al., 2015). Specifically, indicators of executive functioning (i.e., working memory, cognitive flexibility, and inhibition) are often combined into a latent construct of executive functioning as opposed to being evaluated as individual predictors of targeted outcomes. Accordingly, it is important to determine if inhibition is associated with diabetes through anxious arousal and inflammation.
We expected that low inhibition would be associated with high anxious arousal and, in turn, high inflammation. It was predicted that the serial pathway from anxious arousal to inflammation would explain the association between inhibition and diabetes incidence (i.e., serial mediation). Furthermore, we expected that this pathway would remain significant above and beyond other indicators of cognitive abilities (i.e., performance on digit span, backwards counting, and number series measures).
Section snippets
Participants and procedure
Data were obtained from the Midlife Development in the United States (MIDUS) study in which mental and physical health outcomes were examined among a nationally representative sample of middle aged adults. Data from two time points were utilized in the present study. Specifically, measures of cognitive ability described below were completed during a baseline visit. All other measures were completed at the follow-up visit, which occurred an average of 23.39 months (SD = 14.28) after participants
Results
Descriptive statistics are presented in Table 1 and bivariate correlations are presented in Table 2. As expected, better inhibition was associated with less anxious arousal, IL-6, diabetes incidence, and HbA1c. Moreover, all indicators of cognitive ability were significantly positively associated. Furthermore, in line with hypotheses, higher anxious arousal was associated with greater IL-6. As expected, higher IL-6 was associated with a greater likelihood of diabetes incidence and higher HbA1c.
Discussion
Our findings indicate that those with better inhibition evidence lower anxious arousal, IL-6, and HbA1c, in addition to a lower likelihood of meeting criteria for diabetes, than those with poor inhibition. Additionally, those with higher anxious arousal had higher IL-6. As expected, higher IL-6 was associated with higher HbA1c and likelihood of diabetes incidence. In the full model (see Fig. 1), poor inhibition was associated with increased diabetes incidence through the serial pathway from
Conclusions
Consistent with theoretical models linking inhibition, stress, and health, poor inhibition is associated with increased diabetes incidence through the serial pathway from high anxious arousal to high inflammation. These findings have important implications for the prevention and treatment of diabetes by identifying underlying mechanisms contributing to elevated blood glucose.
Contributors
K.W.M was involved in data analysis and manuscript writing for the present study. A.S.L, T.E.L., D.C.D, C.J.H, and C.P.F. provided critical feedback and edited the manuscript.
Role of the funding source
Data collection for the present study was funded by the National Institute on Aging (P01-AG020166). Preparation of the manuscript was supported by a grant from the National Heart, Lung, and Blood Institute (1R01HL127260-01) to C.P.F.
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