Duncan Talbot

Exploration of basal diurnal salivary cortisol profiles in middle-aged adults: Associations with sleep quality and metabolic parameters

The use of saliva samples is a practical and feasible method to explore basal diurnal cortisol profiles in free-living research. This study explores a number of psychological and physiological characteristics in relation to the observed pattern of salivary cortisol activity over a 12-h period with particular emphasis on sleep. Basal diurnal cortisol profiles were examined in a sample of 147 volunteers (mean age 46.21+/-7.18 years). Profiles were constructed for each volunteer and explored in terms of the area under the curve (AUC) of the cortisol-awakening response with samples obtained immediately upon waking (0, 15, 30 and 45 min post waking) and at 3, 6, 9 and 12h post waking to assess diurnal decline. Diurnal mean of cortisol was based on the mean of cortisol at time points 3, 6, 9 and 12h post waking. Psychological measures of perceived stress and sleep were collected with concurrent biological assessment of fasting plasma glucose, insulin, blood lipids and inflammatory markers. Blunted cortisol profiles, characterised by a reduced AUC, were observed in the majority (78%) of a middle-aged sample and were associated with significantly poorer sleep quality and significantly greater waist-hip ratio (WHR). Blunted cortisol profiles were further associated with a tendency to exhibit a less favourable metabolic profile. These findings suggest that reduced cortisol secretion post waking may serve as an additional marker of psychological and biological vulnerability to adverse health outcomes in middle-aged adults.

Assessment of a large panel of candidate biomarkers of ageing in the Newcastle 85+ study

Sensitive and specific biomarkers of ageing are needed to evaluate interventions to extend health span. However, there is growing evidence that information provided by candidate biomarkers may change with age itself. Little is yet known about the value of candidate biomarkers in those over 85 years, currently the fastest growing population sub-group in many countries. This study assessed a large panel of candidate biomarkers in a cohort of 85 years old by studying comparative associations with health status. Using a cross-sectional sample of 852 individuals aged 85, we performed uni- and multi-variable analyses of associations between 74 candidate biomarkers and 4 health-status measures: viz. multi-morbidity, cognitive impairment, disability and proximity to death as measured by mortality within 1.5 years. We defined as most informative any measures that were significantly associated with at least two of the health-status measures in multivariable analyses in this age group. 10 out of 74 tested candidates fulfilled this criterion, while several proposed biomarkers of ageing, notably inflammation and immune risk markers and telomere length, did not. As future data accrues on health outcomes within the cohort, it will become possible also to evaluate the predictive value of these and others of the candidate biomarkers.

Cortisol awakening rise in middle-aged women in relation to psychological stress

OBJECTIVES The cortisol awakening rise (CAR) is defined as cortisol secretory activity in the first 45-60 min immediately post-awakening. It has been suggested that psychological factors may disrupt the normal awakening rise. Recent research has shown that psychological stress may influence the magnitude of the CAR, however the findings have been mixed. This study examined the impact of stress on the CAR and the diurnal mean in a sample of middle-aged women. METHOD One hundred and eighteen healthy female participants who reported experiencing high or low stress were recruited. Salivary cortisol levels were measured immediately upon awakening (at 0, 15, 30, and 45 min) and at 3, 6, 9 and 12 h on two consecutive days. A number of metabolic and inflammatory biomarkers were also assessed together with measures of mood disturbance and health behaviour. RESULTS The magnitude of the CAR, assessed by the area under the response curve (AURC) estimate, was significantly lower in the high stress group compared to the low stress group indicating that participants who experienced high stress secreted lower levels of cortisol. The effect was largely accounted for by differences 30 min after waking. The diurnal mean was also lower for the high stress group. Although participants in the high stress group had a slightly worse inflammatory profile, only low-density lipoprotein levels were found to be significantly higher, compared to the low stress group. Lifestyle indicators and mood were also found to be significantly poorer in the high stress group. CONCLUSIONS The results suggest that psychological stress may be associated with a smaller cortisol awakening rise, a lower diurnal mean, poor lifestyle choices and high levels of psychological distress. These findings may have broader implications for future health risk and for an individuals ability to cope with imminent daily stressors and demands.

Self-Reported Sitting Time and Markers of Inflammation, Insulin Resistance, and Adiposity

BACKGROUND Sedentary behavior is emerging as an independent risk factor for chronic disease; however, potential mechanisms underpinning these observations are not well understood. PURPOSE This study aimed to investigate the association of self-reported weekday sitting time with biomarkers linked to chronic low-grade inflammation, insulin resistance, and adiposity. METHODS This study reports data from individuals attending a diabetes screening program, United Kingdom, 2004-2007; analysis was conducted in 2010. Sitting time and physical activity were measured using the International Physical Activity Questionnaire; biochemical outcomes included fasting and 2-hour postchallenge glucose, fasting insulin, C-reactive protein (CRP), leptin, adiponectin, and interleukin-6 (IL-6). RESULTS This study included 505 (female=46%; South-Asian ethnicity=19%, aged 59±10 years, BMI=29.5±4.7) individuals with valid sitting data. Increased sitting time was positively associated with fasting insulin, leptin, leptin/adiponectin ratio, CRP, and IL-6 in women, but not men, after adjustment for age, ethnicity, social deprivation, and smoking and medication status; interaction analysis revealed that the gender-specific differences were significant. The associations for women remained significant after additional adjustment for total moderate- to vigorous-intensity physical activity; however all associations were attenuated when further adjusted for BMI. There was no association between sitting time and glycemic status. CONCLUSIONS Total self-reported weekday sitting time was associated with biomarkers linked to chronic low-grade inflammation and poor metabolic health in women, but not men, independent of physical activity.

Sedentary Time and Markers of Chronic Low-Grade Inflammation in a High Risk Population

Background Sedentary behaviour has been identified as a distinct risk factor for several health outcomes. Nevertheless, little research has been conducted into the underlying mechanisms driving these observations. This study aimed to investigate the association of objectively measured sedentary time and breaks in sedentary time with markers of chronic low-grade inflammation and adiposity in a population at a high risk of type 2 diabetes mellitus. Methods This study reports data from an ongoing diabetes prevention programme conducted in Leicestershire, UK. High risk individuals were recruited from 10 primary care practices. Sedentary time (<25counts per 15s) was measured using Actigraph GT3X accelerometers (15s epochs). A break was considered as any interruption in sedentary time (≥25counts per 15s). Biochemical outcomes included interleukin-6 (IL-6), C-reactive protein (CRP), leptin, adiponectin and leptin:adiponectin ratio (LAR). A sensitivity analysis investigated whether results were affected by removing participants with a CRP level >10 mg/L, as this can be indicative of acute inflammation. Results 558 participants (age = 63.6±7.7years; male = 64.7%) had complete adipokine and accelerometer data. Following adjustment for various confounders, sedentary time was detrimentally associated with CRP (β = 0.176±0.057, p = 0.002), IL-6 (β = 0.242±0.056, p = <0.001), leptin (β = 0.146±0.043, p = <0.001) and LAR (β = 0.208±0.052, p = <0.001). Associations were attenuated after further adjustment for moderate-to-vigorous physical activity (MVPA) with only IL-6 (β = 0.231±0.073, p = 0.002) remaining significant; this result was unaffected after further adjustment for body mass index and glycosylated haemoglobin (HbA1c). Similarly, breaks in sedentary time were significantly inversely associated with IL-6 (β = −0.094±0.047, p = 0.045) and leptin (β = −0.075±0.037, p = 0.039); however, these associations were attenuated after adjustment for accelerometer derived variables. Excluding individuals with a CRP level >10 mg/L consistently attenuated the significant associations across all markers of inflammation. Conclusion These novel findings from a high risk population recruited through primary care suggest that sedentary behaviour may influence markers associated with inflammation, independent of MVPA, glycaemia and adiposity.

MARK-AGE biomarkers of ageing

Many candidate biomarkers of human ageing have been proposed in the scientific literature but in all cases their variability in cross-sectional studies is considerable, and therefore no single measurement has proven to serve a useful marker to determine, on its own, biological age. A plausible reason for this is the intrinsic multi-causal and multi-system nature of the ageing process. The recently completed MARK-AGE study was a large-scale integrated project supported by the European Commission. The major aim of this project was to conduct a population study comprising about 3200 subjects in order to identify a set of biomarkers of ageing which, as a combination of parameters with appropriate weighting, would measure biological age better than any marker in isolation.

Effect of consumption of soy isoflavones on behavioural, somatic and affective symptoms in women with premenstrual syndrome

Up to 80 % of the Western female population experience premenstrual syndrome (PMS). Long-term pharmacological therapy is unacceptable to most women, and is not warranted for moderate symptoms. Nutritional therapies are popular, but lack a clear evidence base. Anecdotal evidence suggests beneficial effects of soy isoflavones because of their influence on endogenous oestrogen and actions on specific tissues. The effect of isolated soya protein (ISP) containing 68 mg/d (aglycone equivalents) soy isoflavones (IF) on premenstrual symptom severity was studied in a seven-menstrual cycle, double-blind, placebo-controlled, crossover intervention study in twenty-three women with prospectively confirmed PMS aged 18-35 years and BMI 19-30 kg/m(2). ISP containing IF or milk protein placebo was consumed for two complete menstrual cycles. ISP containing IF (genistein, daidzein, equol) were measured in 24 h urine samples. After two cycles of ISP containing IF intervention, total symptoms (F(2,36) 8.20, P=0.000) and physical symptoms (F(2,36) 8.18, P=0.000) were significantly reduced compared with baseline after both active and placebo treatments, although differences between active and placebo treatment were non-significant. Specific premenstrual symptoms, headache (F(2,32) 4.10, P=0.026) and breast tenderness (F(2,32) 4.59, P=0.018), were reduced from baseline after soy IF, but not milk protein placebo. Cramps (F(2,32) 4.15, P=0.025) and swelling (F(2,32) 4.64, P=0.017) were significantly lower after active treatment compared with placebo. Concentrations of genistein and daidzein were increased following soy IF consumption, but equol production did not enhance symptom reduction. The present study showed that ISP containing IF may have potential to reduce specific premenstrual symptoms via non-classical actions.

Behavioral Neurocardiac Training in Hypertension A Randomized, Controlled Trial

It is not established whether behavioral interventions add benefit to pharmacological therapy for hypertension. We hypothesized that behavioral neurocardiac training (BNT) with heart rate variability biofeedback would reduce blood pressure further by modifying vagal heart rate modulation during reactivity and recovery from standardized cognitive tasks (“mental stress”). This randomized, controlled trial enrolled 65 patients with uncomplicated hypertension to BNT or active control (autogenic relaxation), with six 1-hour sessions over 2 months with home practice. Outcomes were analyzed with linear mixed models that adjusted for antihypertensive drugs. BNT reduced daytime and 24-hour systolic blood pressures (−2.4±0.9 mm Hg, P=0.009, and −2.1±0.9 mm Hg, P=0.03, respectively) and pulse pressures (−1.7±0.6 mm Hg, P=0.004, and −1.4±0.6 mm Hg, P=0.02, respectively). No effect was observed for controls (P>0.10 for all indices). BNT also increased RR-high-frequency power (0.15 to 0.40 Hz; P=0.01) and RR interval (P<0.001) during cognitive tasks. Among controls, high-frequency power was unchanged (P=0.29), and RR interval decreased (P=0.03). Neither intervention altered spontaneous baroreflex sensitivity (P>0.10). In contrast to relaxation therapy, BNT with heart rate variability biofeedback modestly lowers ambulatory blood pressure during wakefulness, and it augments tonic vagal heart rate modulation. It is unknown whether efficacy of this treatment can be improved with biofeedback of baroreflex gain. BNT, alone or as an adjunct to drug therapy, may represent a promising new intervention for hypertension.

The effect of increased ambulatory activity on markers of chronic low-grade inflammation: evidence from the PREPARE programme randomized controlled trial.

Diabet. Med. 27, 1256–1263 (2010)

Stress-related thinking predicts the cortisol awakening response and somatic symptoms in healthy adults.

OBJECTIVE Perseverative cognition (i.e., worry, stress-related thinking) may prolong stress-related physiological activation. However, its role within the context of the written emotional disclosure paradigm has not been examined. This study explored: (1) the effects of stress-related thinking on the cortisol awakening response and upper respiratory infection symptoms and; (2) the efficacy of two expressive writing interventions on these health outcomes. METHODS Participants were randomly assigned to write about their most stressful life experience (using the Guided Disclosure Protocol; n=39) or positive life experiences (n=42) or plans for the day (n=41) for 20 min on 3 consecutive days. Participants reported the extent to which they thought about their assigned writing topic during the study and in the past (event-related thought). Cortisol was measured at 0, 15, 30 and 45 min after awakening on 2 consecutive days at baseline and 4 weeks post-intervention. Upper respiratory infection (URI) symptoms were assessed at baseline, at 4 weeks and at 6 months. RESULTS Results showed that the writing interventions had no beneficial effects on any of the outcome measures. However, a significant interaction was found between event-related thought and condition on the cortisol awakening response at 1 month follow-up and URI symptoms at 6 months. Among participants who wrote about stressful/traumatic events, higher stress-related thinking during the study predicted increased cortisol levels and URI symptoms compared to participants who reported low stress-related thinking. DISCUSSION These findings are broadly consistent with Brosschot et al.s (2006) perseverative cognition hypothesis and highlight the importance of ruminative thinking in understanding stress-health processes.