Ruth A. Hackett

Loneliness and stress-related inflammatory and neuroendocrine responses in older men and women.

Loneliness is a predictor of mortality and increased cardiovascular morbidity. Inflammation is a potential pathway through which loneliness might impact health. The aim of the study was to investigate the relationship between loneliness and inflammatory interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra) and monocyte chemotactic protein-1 (MCP-1) responses to standardized mental stress. A secondary purpose was to evaluate whether individual variations in cortisol responses influenced the hypothesised relationship between loneliness and inflammation. Saliva samples and blood were taken from 524 healthy middle-aged men and women from the Whitehall II cohort at baseline, immediately after the stress tasks and 45min later. Loneliness was measured using the revised UCLA loneliness scale. Greater loneliness was associated with larger IL-6 (p=0.044) and IL-1Ra (p=0.006) responses to psychological stress and higher MCP-1 (p<0.001) levels in women, independently of age, grade of employment, body mass index and smoking status. No associations were observed in men. Cortisol responsivity was inversely related to loneliness in women, with the odds of being a cortisol responder decreasing with increased loneliness independently of covariates (p=0.008). The impact of loneliness on health in women may be mediated in part through dysregulation of inflammatory and neuroendocrine systems.

Disruption of multisystem responses to stress in type 2 diabetes: Investigating the dynamics of allostatic load

Significance Our observations provide evidence to link epidemiological studies implicating stress-related processes with biological dysfunction in type 2 diabetes. The patterns of cardiovascular, inflammatory, neuroendocrine, and cholesterol responses exemplify the disturbances of reactivity and recovery predicted by the allostatic load model, including prolonged responses to stress due to delayed shutdown of physiological reactivity, and inadequate (blunted) responses resulting in compensatory hyperactivity in other mediating pathways. Chronic allostatic load may be a mechanism through which stress exposures contribute to diabetes risk, while also being implicated in the adverse health consequences of diabetes such as coronary heart disease and cognitive decline. Psychological stress-related processes are thought to contribute to the development and progression of type 2 diabetes, but the biological mechanisms involved are poorly understood. Here, we tested the notion that people with type 2 diabetes experience chronic allostatic load, manifest as dynamic disturbances in reactivity to and recovery from stress across multiple (cardiovascular, neuroendocrine, inflammatory, metabolic) biological systems, coupled with heightened experience of chronic life stress. We carried out an experimental comparison of 140 men and women aged 50–75 y with type 2 diabetes and 280 nondiabetic individuals matched on age, sex, and income. We monitored blood pressure (BP) and heart rate, salivary cortisol, plasma interleukin (IL)-6, and total cholesterol in response to standardized mental stress, and assessed salivary cortisol over the day. People with type 2 diabetes showed impaired poststress recovery in systolic and diastolic BP, heart rate and cholesterol, and blunted stress reactivity in systolic BP, cortisol, cholesterol, and IL-6. Cortisol and IL-6 concentrations were elevated, and cortisol measured over the day was higher in the type 2 diabetes group. Diabetic persons reported greater depressive and hostile symptoms and greater stress experience than did healthy controls. Type 2 diabetes is characterized by disruption of stress-related processes across multiple biological systems and increased exposure to life stress. Chronic allostatic load provides a unifying perspective with implications for etiology and patient management.

Association of Diurnal Patterns in Salivary Cortisol With Type 2 Diabetes in the Whitehall II Study

CONTEXT The hypothalamic pituitary-adrenal axis is thought to play a role in Type 2 Diabetes (T2D). However, the evidence for an association between diurnal cortisol patterns and T2D is equivocal. OBJECTIVE The aim was to examine the association of cortisol patterns throughout the day with T2D status in a community-dwelling population. DESIGN This was a cross-sectional study of T2D status and salivary cortisol from phase 7 (2002-2004) of the Whitehall II study, United Kingdom. SETTING The occupational cohort was originally recruited in 1985-1988. PARTICIPANTS Three-thousand, five-hundred eight white men and women including 238 participants with T2D aged 50-74 years with complete information on cortisol secretion participated. OUTCOME MEASURES We measured diurnal cortisol (nmol/L) patterns from six saliva samples obtained over the course of a normal day: at waking, +30 min, +2.5, +8, +12 hours, and bedtime. The cortisol awakening response and slope in diurnal secretion were calculated. RESULTS T2D status was associated with a flatter slope in cortisol decline across the day (b = 0.004; confidence interval [CI], 0.001-0.007; P = .014) and greater bedtime cortisol (b = 0.063; CI, 0.010-0.117; P = 0.020) independent of a wide range of covariates measured at the time of cortisol assessment. There was no association between morning cortisol, the cortisol awakening response, and T2D (P > .05). CONCLUSIONS In this nonclinical population, T2D was associated with a flatter slope in cortisol levels across the day and raised bedtime cortisol values.

Diurnal Cortisol Patterns, Future Diabetes, and Impaired Glucose Metabolism in the Whitehall II Cohort Study

CONTEXT The hypothalamic pituitary-adrenal axis is thought to play a role in type 2 diabetes (T2D). However, evidence for an association between cortisol and future glucose disturbance is sparse. OBJECTIVE The aim was to examine the association of diurnal cortisol secretion with future T2D and impaired glucose metabolism in a community-dwelling population. DESIGN This is a prospective cohort study of salivary cortisol measured at the 2002-2004 clinical examination of the Whitehall II study, United Kingdom. We measured cortisol (nmol/l) from six saliva samples obtained over the course of a day: at waking, +30 minutes, +2.5 hours, +8 hours, +12 hours, and bedtime. Participants who were normoglycemic in 2002-2004 (phase 7) were reexamined in 2012-2013 (phase 11). SETTING The occupational cohort was originally recruited in 1985-1988. PARTICIPANTS A total of 3270 men and women with an average age of 60.85 years at phase 7 (2002-2004). OUTCOME MEASURES Incident T2D and impaired fasting glucose in 2012-2013 were measured. RESULTS Raised evening cortisol at phase 7 was predictive of new-onset T2D at phase 11 (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.01-1.37) with a trend for a flatter slope in participants with incident T2D (odds ratio, 1.15; 95% CI, 0.99-1.33). When expanding this analysis to a broader category of glucose disturbance we found that a flattened diurnal cortisol slope at phase 7 was predictive of future impaired fasting glucose or T2D at phase 11 (OR, 1.12; 95% CI, 1.02-1.22), as was high bedtime cortisol (OR, 1.10; 95% CI, 1.01-1.20). CONCLUSIONS In this nonclinical population, alterations in diurnal cortisol patterns were predictive of future glucose disturbance.

Type 2 diabetes mellitus and psychological stress — a modifiable risk factor

Psychological stress is common in many physical illnesses and is increasingly recognized as a risk factor for disease onset and progression. An emerging body of literature suggests that stress has a role in the aetiology of type 2 diabetes mellitus (T2DM) both as a predictor of new onset T2DM and as a prognostic factor in people with existing T2DM. Here, we review the evidence linking T2DM and psychological stress. We highlight the physiological responses to stress that are probably related to T2DM, drawing on evidence from animal work, large epidemiological studies and human laboratory trials. We discuss population and clinical studies linking psychological and social stress factors with T2DM, and give an overview of intervention studies that have attempted to modify psychological or social factors to improve outcomes in people with T2DM.

Blunted glucocorticoid and mineralocorticoid sensitivity to stress in people with diabetes

Highlights • Impaired stress responsivity in type 2 diabetes is associated with a lack of mineralocorticoid and glucocorticoid sensitivity.• Corticosteroid sensitivity in type 2 diabetes correlates to HbA1c.• Type 2 diabetes participants showed blunted response to stress in inflammatory cytokines.

Psychosocial Factors in Diabetes and Cardiovascular Risk

Type 2 diabetes is a chronic disease that is increasing in prevalence globally. Cardiovascular disease is a major cause of mortality and morbidity in diabetes, and lifestyle and clinical risk factors do not fully account for the link between the conditions. This article provides an overview of the evidence concerning the role of psychosocial stress factors in diabetes risk, as well as in cardiovascular complications in people with existing diabetes. Several types of psychosocial factors are discussed including depression, other types of emotional distress, exposure to stressful conditions, and personality traits. The potential behavioral and biological pathways linking psychosocial factors to diabetes are presented and implications for patient care are highlighted.

Optimism moderates psychophysiological responses to stress in older people with Type 2 diabetes

Abstract Optimism is thought to be beneficial for health, and these effects may be mediated through modifications in psychophysiological stress reactivity. Type 2 diabetes (T2D) is associated with reduced cardiovascular responses to stress and heightened cortisol over the day. This study assessed the relationships between optimism, stress responsivity, and daily cortisol output in people with T2D. A total of 140 participants with T2D were exposed to laboratory stress. Heart rate (HR), systolic (SBP), diastolic blood pressure (DBP), and cortisol were measured throughout the session. Cortisol output over the day was also assessed. Optimism and self‐reported health were measured using the revised Life Orientation Test and the Short Form Health Survey. Optimism was associated with heightened SBP and DBP stress reactivity (ps < .047) and lower daily cortisol output (p = .04). Optimism was not related to HR, cortisol stress responses, or the cortisol awakening response (ps > .180). Low optimism was related to poorer self‐reported physical and mental health (ps < .01). Optimism could have a protective role in modulating stress‐related autonomic and neuroendocrine dysregulation in people with T2D.

Hostility and Physiological Responses to Acute Stress in People With Type 2 Diabetes

Objective Hostility is associated with cardiovascular mortality and morbidity, and one of the mechanisms may involve heightened reactivity to mental stress. However, little research has been conducted in populations at high risk for cardiovascular disease. The aim of the present study was to assess the relationship between hostility and acute stress responsivity in individuals with Type 2 diabetes. Methods A total of 140 individuals (median age [standard deviation] 63.71 [7.00] years) with Type 2 diabetes took part in laboratory-based experimental stress testing. Systolic blood pressure, diastolic blood pressure, heart rate, plasma interleukin-6 (IL-6), and salivary cortisol were assessed at baseline, during two stress tasks, and 45 and 75 minutes later. Cynical hostility was assessed using the Cook Medley Cynical Hostility Scale. Results Participants with greater hostility scores had heightened increases in IL-6 induced by the acute stress tasks (B = 0.082, p = .002), independent of age, sex, body mass index, smoking, household income, time of testing, medication, and baseline IL-6. Hostility was inversely associated with cortisol output poststress (B = −0.017, p = .002), independent of covariates. No associations between hostility and blood pressure or heart rate responses were observed. Conclusions Hostile individuals with Type 2 diabetes may be susceptible to stress-induced increases in inflammation. Further research is needed to understand if such changes increase the risk of cardiovascular disease in this population.

Objectively assessed physical activity, adiposity, and inflammatory markers in people with type 2 diabetes

Objective Inflammatory processes may play an important role in the development of acute coronary syndromes in people with type 2 diabetes; thus, strategies to control inflammation are of clinical importance. We examined the cross-sectional association between objectively assessed physical activity and inflammatory markers in a sample of people with type 2 diabetes. Methods Participants were 71 men and 41 women (mean age=63.9±7 years), without a history of cardiovascular disease, drawn from primary care clinics. Physical activity was objectively measured using waist-worn accelerometers (Actigraph GT3X) during waking hours for seven consecutive days. Results We observed inverse associations between moderate-to-vigorous physical activity (per 10 min) with plasma interleukin-6 (B=−0.035, 95% CI −0.056 to −0.015), interleukin-1ra (B=−0.033, 95% CI −0.051 to −0.015), and monocyte chemotactic protein-1 (B=−0.011, 95% CI −0.021 to 0.000). These associations largely persisted in multivariable adjusted models, although body mass index considerably attenuated the effect estimate. Conclusions These data demonstrate an inverse association between physical activity and inflammatory markers in people with type 2 diabetes.