Natasha Bergmann

The appraisal of chronic stress and the development of the metabolic syndrome: a systematic review of prospective cohort studies.

Chronic psychosocial stress has been proposed as a risk factor for the development of the metabolic syndrome (MES). This review gives a systematic overview of prospective cohort studies investigating chronic psychosocial stress as a risk factor for incident MES and the individual elements of MES. Thirty-nine studies were included. An association between chronic psychosocial stress and the development of MES was generally supported. Regarding the four elements of MES: i) weight gain: the prospective studies supported etiological roles for relationship stress, perceived stress, and distress, while the studies on work-related stress (WS) showed conflicting results; ii) dyslipidemi: too few studies on psychosocial stress as a risk factor for dyslipidemia were available to draw a conclusion; however, a trend toward a positive association was present; iii) type 2 diabetes mellitus (DM2): prospective studies supported perceived stress and distress as risk factors for the development of DM2 among men, but not among women, while WS was generally not supported as a risk factor among neither men nor women; iv) hypertension: marital stress and perceived stress might have an influence on blood pressure (BP), while no association was found regarding distress. Evaluating WS the results were equivocal and indicated that different types of WS affected the BP differently between men and women. In conclusion, a longitudinal association between chronic psychosocial stress and the development of MES seems present. However, the number of studies with sufficient quality is limited and the design of the studies is substantially heterogeneous.

Diabetes and obesity treatment based on dual incretin receptor activation: ‘twincretins’

The gut incretin hormones glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) are secreted after meal ingestion and work in concert to promote postprandial insulin secretion and regulate glucagon secretion. GLP‐1 also slows gastric emptying and suppresses appetite, whereas GIP seems to affect lipid metabolism. The introduction of selective GLP‐1 receptor (GLP‐1R) agonists for the treatment of type 2 diabetes and obesity has increased the scientific and clinical interest in incretins. Combining the body weight‐lowering and glucose‐lowering effects of GLP‐1 with a more potent improvement of β cell function through additional GIP action could potentially offer a more effective treatment of diabetes and obesity, with fewer adverse effects than selective GLP‐1R agonists; therefore, new drugs designed to co‐activate both the GIP receptor (GIPR) and the GLP‐1R simultaneously are under development. In the present review, we address advances in the field of GIPR and GLP‐1R co‐agonism and review in vitro studies, animal studies and human trials involving co‐administration of the two incretins, as well as results from a recently developed GIPR/GLP‐1R co‐agonist, and highlight promising areas and challenges within the field of incretin dual agonists.

The Effect of Daily Self-Measurement of Pressure Pain Sensitivity Followed by Acupressure on Depression and Quality of Life versus Treatment as Usual in Ischemic Heart Disease: A Randomized Clinical Trial

Background Depressive symptoms and reduced quality of life (QOL) are parts of the chronic stress syndrome and predictive of adverse outcome in patients with ischemic heart disease (IHD). Chronic stress is associated with increased sensitivity for pain, which can be measured by algometry as Pressure Pain Sensitivity (PPS) on the sternum. Aim To evaluate if stress focus by self-measurement of PPS, followed by stress reducing actions including acupressure, can decrease depressive symptoms and increase psychological well-being in people with stable IHD. Design Observer blinded randomized clinical trial over 3 months of either intervention or treatment as usual (TAU). Statistical analysis: Intention to treat. Methods Two hundred and thirteen participants with IHD were included: 106 to active treatment and 107 to TAU. Drop-out: 20 and 12, respectively. The active intervention included self-measurement of PPS twice daily followed by acupressure as mandatory action, aiming at a reduction in PPS. Primary endpoint: change in depressive symptoms as measured by Major depression inventory (MDI). Other endpoints: changes in PPS, Well-being (WHO-5) and mental and physical QOL (SF-36). Results At 3 months PPS decreased 28%, to 58, in active and 11%, to 72, in TAU, p<0.001. MDI decreased 22%, to 6.5, in active group vs. 12%, to 8.3 in TAU, p = 0.040. WHO-5 increased to 71.0 and 64.8, active group and TAU, p = 0.015. SF-36 mental score sum increased to 55.3 and 53.3, active and TAU, p = 0.08. Conclusions PPS measurements followed by acupressure reduce PPS, depressive symptoms and increase QOL in patients with stable IHD. Trial Registration ClinicalTrials.gov NCT01513824

Pressure pain sensitivity: a new method of stress measurement in patients with ischemic heart disease.

Abstract Background. Chronic stress is prevalent in patients with ischemic heart disease (IHD) and worsens the long-term prognosis. Chronic stress is vaguely defined, but is associated with depressive symptoms, reduced psychological wellbeing, and reduced quality of life (QOL). Stress seems to induce hyperalgesia.The aim of the present study was to evaluate hyperalgesia by pressure pain sensitivity (PPS) in patients with IHD, and compare PPS to questionnaires measuring depressive symptoms, reduced psychological wellbeing, and QOL as markers of stress. Design. A cross-sectional study of 361 subjects with IHD. Methods. PPS was measured on the sternum, and compared to the questionnaires: Clinical stress symptoms score (CSS), Major Depression Inventory (MDI), WHO-5 Wellbeing Index, and SF-36 QOL score. Results. PPS correlated to CSS (r = 0.20, p < 0.001), MDI (r = 0.14, p = 0.02), SF-36 mental component summary score (MCS) (r = − 0.10, p = 0.049), SF-36 physical component summary score (PCS) (r = − 0.17, p = 0.001), and self-perceived stress level (r = 0.15, p = 0.006). CSS correlated similarly (r = 0.5–0.7, all p < 0.001). Comparing subjects within the lowest vs. highest tertiles of PPS and CSS, the mean MDI score was 4 vs. 15, WHO-5 was 77 vs. 53, SF-36 PCS was 53 vs. 43, and SF-36 MCS was 58 vs. 46; all p < 0.001. Conclusions. PPS reflected to a modest degree markers of chronic stress in IHD. PPS and CSS together might be useful as easy-to use tools for evaluating these markers in IHD patients.

Incidence rate of symptomatic painless thyroiditis presenting with thyrotoxicosis in Denmark as evaluated by consecutive thyroid scintigraphies

Abstract Background. Painless thyroiditis (PT) is a transient kind of thyrotoxicosis, with lack of uptake on a thyroid scintigraphy in a non-tender thyroid gland, elevated anti-TPO antibodies, no fever, no history of increased iodine intake, and a normal sedimentation rate. The prevalence of PT varies hugely in the literature. Objective. To establish the incidence rate of PT in Denmark as well as to describe the phenotype of PT in more detail. Methods. Tc-99m pertechnetate scintigraphies were performed over a period of 9.75 years on 6022 consecutive patients (2349 had a thyrotoxic episode), and were divided into high or normal (5528), reduced (300) or lack of uptake (194). Patient records were evaluated: 292 with reduced, and 186 with lack of uptake. As a control measure, 230 consecutive thyrotoxic patients were also analyzed. Results. Based on scintigraphies, 12 patients had PT, 10 with lack of uptake and two with reduced, corresponding to an incidence rate of 0.49/100,000 person years. It was predicted, that only one patient among the newly diagnosed consecutive thyrotoxic cohort had PT. This patient was identified. The prevalence of PT among thyrotoxic patients was 0.51% as evaluated by scintigraphy, and 0.43% among the biochemically thyrotoxic patient cohort. Twenty-five percent had more than one thyrotoxic episode, 75% had at least one subsequent hypothyroid episode, and 33% developed permanent hypothyroidism. Conclusions. PT presenting with symptomatic thyrotoxicosis is an extremely rare disease in Denmark. Symptomatic PT presents most often with no uptake on a Tc-99m pertechnetate scintigraphy. Clinical follow-up is essential.

Chronic psychological stress seems associated with elements of the metabolic syndrome in patients with ischaemic heart disease

Abstract Background and objectives: Chronic psychological stress, the metabolic syndrome (MS) and ischaemic heart disease (IHD) seem closely connected. In this study, we evaluate the association between chronic stress and elements of MS in patients with stable IHD. Design: Cross-sectional cohort study. Methods: Three hundred and fifty patients with stable IHD were included. Chronic stress was evaluated by the two questionnaires, Major Depression Inventory (MDI) and the psychological wellbeing index WHO-5, as well as by Pressure Pain Sensitivity (PPS), a physiological measure of hyperalgesia at the sternum known to be associated to elements of the chronic stress syndrome. Elements of MS were evaluated by dual-energy X-ray absorptiometry, body weight, HOMA-IR and blood lipids. Results: Depressive symptoms were associated with a high percentage of body fat (β = 0.179, p = .001), and high level of triglycerides (β = 0.150, p = .007). Low psychological wellbeing was associated with a high percentage of body fat (β = –0.165, p = .002) and low level of HDL cholesterol (β = 0.128, p = .024). Chronic stress measured by PPS was associated with a high percentage body fat (β = 0.327, p < .001), low body weight (β = –0.218, p < .001) and low HDL-cholesterol (β = –0.137, p = .013). Adjusting for several life style factors did not change these results. Conclusions: In patients with stable IHD, different measures of chronic psychological stress seem associated with a high percentage of body fat and adverse blood lipids independent of several lifestyle factors.

Association between pressure pain sensitivity and autonomic function as assessed by a tilt table test

Abstract Background. We tested the hypothesis that pressure sensitivity of the sternum (PPS) is associated with autonomic nervous system (ANS) function as assessed by tilt table test (TTT). in patients with stable ischemic heart disease. Objectives. (1) To evaluate an association between PPS and systolic blood pressure (SBP) and heart rate (HR) responses to TTT; and (2) to test the hypothesis that a reduction of resting PPS raises the PPS, SBP and HR responses to TTT response and lowers risk factors for ANS dysfunction (ANSD). Methods. Cross-sectional study: In 361 patients with stable ischemic heart disease we measured PPS, SBP, and HR during TTT. Intervention study: We reassessed subjects with persistent stress who concluded a stress intervention trial by a second TTT. Results. Cross-sectional study: Resting PPS and the PPS response to TTT were correlated (r = − 0.37). The PPS response to TTT was correlated with that of SBP (r = 0.44) and HR (r = 0.49), and with the number of risk factors for ANSD (r = − 0.21) (all p < 0.0001). Intervention study: A reduction in resting PPS was associated with an increment in PPS response to TTT (r = − 0.52, p < 0.0001). The greater this increment, the greater was the reduction in ANSD risk factors (r = − 0.23; p = 0.003). Conclusion. The results are consistent with the hypothesis that PPS at rest and in response to TTT reflects ANS function.

Diabetes and ischemic heart disease: double jeopardy with regard to depressive mood and reduced quality of life

The aim of this study was to test i) whether patients having diabetes and ischemic heart disease (IHD), i.e., patients suffering from two chronic diseases, demonstrate a higher degree of chronic stress when compared with patients suffering from IHD alone, and ii) whether suffering from the two chronic diseases results in an elevation in specific elements of the chronic stress concept. A total of 361 participants with IHD were included, of whom 47 suffered from concomitant diabetes. Stress was measured by pressure pain sensitivity (PPS) and by the following questionnaires: the Major Depression Inventory (MDI), the SF-36 Quality of Life questionnaire (SF-36 QOL), the WHO-5 Well-being Index, and the clinical stress signs (CSSs) scale. Participants with diabetes and IHD had a higher MDI score, a lower SF-36 physical component summary score, and a lower score of several sub-measurements of the SF-36 mental component score when compared with patients with IHD without diabetes. No significant differences were observed regarding stress measured by the PPS measure, the WHO-5 Well-being Index, or the number of CSSs. In conclusion, the combination of diabetes and IHD seems to be associated with increased depressive symptoms, lower overall physical QOL, and reduced mental QOL on several sub-elements of the questionnaire. This should be recognized in the management of patients with double diagnoses.

Pressure pain sensitivity

Introduction: the relationship between psychiatric symptoms and cancer has sparked a lot of interest in the scientific community. The available literature is mostly on the impact of cancer diagnosis. However, little is known about the patients psychological status before that. Studies in this area show that cancer patients often present depressive symptoms before the diagnosis of neoplastic disease, probably due to cytokine production by the tumors. Low concentrations of cytokines would be sufficient to change the patient’s emotional state. Case description: to alert clinicians to the possibility that psychiatric symptoms may be a signal of underlying cancer disease, especially in patients above 50 years without psychiatric history, we present the following case. A woman of 53 years, followed in the Portuguese Institute of Oncology of Coimbra since October 2009 for mixed adenocarcinoma of the lung (stage IB). Approximately 1 month later, in November 2009, she was referred to psychiatric consultation because of depressive symptoms and complains since 1 year before. She also reported history of thyroid goiter, emphysema, and depressive episode occurred 10 years begore. Since the cancer was diagnosed, depression has shown a fluctuating evolution. Various therapeutic settings were made, being currently medicated with venlafaxine 225 mg, trazodone 150 mg AC i.d., and lorazepam 2.5 mg i.d.. Comment: the emergence of psychiatric symptoms, especially in patients above 50 years, should alert the physician to the presence of a possible hidden cancer, especially in the case of patients without psychiatric history.Introduction: Stress has been hypothesized to be involved in obesity development. Apart from a direct pathway through cortisol, stress may indirectly facilitate obesity by influencing other lifestyle factors: stressed persons may consume more comfort foods, may have a more sedentary behaviour and may suffer from sleep problems. Methods: In 326 Belgian children (5-12y) of the ChiBS study, the longitudinal relation between stress and body composition was examined over two years. Stress was measured by salivary cortisol (4 samples/day, 2 days) and questionnaires concerning negative life events, problem behaviour and emotions. For body composition, BMI, waist-to-height and fat% estimation by air displacement were used. Furthermore, physical activity, screentime, food consumption, eating behaviour and sleep duration were measured as lifestyle factors. Cross-lagged analyses with Mplus and moderation by cortisol and lifestyle factors were tested. Results: Children with higher stress scores had a less healthy lifestyle. They had an unhealthier diet especially due to more sweet food consumption, performed more emotional eating, were less active and slept less. Two years later, these stressed children maintained the same unhealthy life style except that they were more physical active instead of less. Salivary cortisol and lifestyle were moderators in the stress-obesity relation: stressed children had also more overweight or a higher fat percentage, but only when they had an unhealthier lifestyle or higher cortisol. Discussion: These results confirm that stress can deteriorate lifestyle and cortisol homeostasis already in childhood and that these changes make them vulnerable to overweight. Consequently, obesity prevention should target both lifestyle and stress.

Pressure pain sensitivity: a new method of stress 2 measurement in patients with ischemic heart disease

Introduction: the relationship between psychiatric symptoms and cancer has sparked a lot of interest in the scientific community. The available literature is mostly on the impact of cancer diagnosis. However, little is known about the patients psychological status before that. Studies in this area show that cancer patients often present depressive symptoms before the diagnosis of neoplastic disease, probably due to cytokine production by the tumors. Low concentrations of cytokines would be sufficient to change the patient’s emotional state. Case description: to alert clinicians to the possibility that psychiatric symptoms may be a signal of underlying cancer disease, especially in patients above 50 years without psychiatric history, we present the following case. A woman of 53 years, followed in the Portuguese Institute of Oncology of Coimbra since October 2009 for mixed adenocarcinoma of the lung (stage IB). Approximately 1 month later, in November 2009, she was referred to psychiatric consultation because of depressive symptoms and complains since 1 year before. She also reported history of thyroid goiter, emphysema, and depressive episode occurred 10 years begore. Since the cancer was diagnosed, depression has shown a fluctuating evolution. Various therapeutic settings were made, being currently medicated with venlafaxine 225 mg, trazodone 150 mg AC i.d., and lorazepam 2.5 mg i.d.. Comment: the emergence of psychiatric symptoms, especially in patients above 50 years, should alert the physician to the presence of a possible hidden cancer, especially in the case of patients without psychiatric history.Introduction: Stress has been hypothesized to be involved in obesity development. Apart from a direct pathway through cortisol, stress may indirectly facilitate obesity by influencing other lifestyle factors: stressed persons may consume more comfort foods, may have a more sedentary behaviour and may suffer from sleep problems. Methods: In 326 Belgian children (5-12y) of the ChiBS study, the longitudinal relation between stress and body composition was examined over two years. Stress was measured by salivary cortisol (4 samples/day, 2 days) and questionnaires concerning negative life events, problem behaviour and emotions. For body composition, BMI, waist-to-height and fat% estimation by air displacement were used. Furthermore, physical activity, screentime, food consumption, eating behaviour and sleep duration were measured as lifestyle factors. Cross-lagged analyses with Mplus and moderation by cortisol and lifestyle factors were tested. Results: Children with higher stress scores had a less healthy lifestyle. They had an unhealthier diet especially due to more sweet food consumption, performed more emotional eating, were less active and slept less. Two years later, these stressed children maintained the same unhealthy life style except that they were more physical active instead of less. Salivary cortisol and lifestyle were moderators in the stress-obesity relation: stressed children had also more overweight or a higher fat percentage, but only when they had an unhealthier lifestyle or higher cortisol. Discussion: These results confirm that stress can deteriorate lifestyle and cortisol homeostasis already in childhood and that these changes make them vulnerable to overweight. Consequently, obesity prevention should target both lifestyle and stress.