ABSTRACT
PURPOSE: Impaired negative feedback and hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis characterizes type 2 diabetes mellitus (T2DM). The glucocorticoid receptor (GR) is a key mediator of HPA axis negative feedback; however, its role in linking hypercortisolemia and T2DM-associated hyperglycemia, hyperlipidemia and inflammation is not yet known. METHODS: In peripheral mononuclear cells (PBMC) from 31 T2DM patients and 24 healthy controls, we measured various GR-signaling parameters such as phosphorylated GR (pGR-S211), GRα/GRß gene expression and GC-sensitivity [using the basal and dexamethasone (DEX)-induced leucine zipper (GILZ) and FK506 binding-protein (FKBP5) mRNA levels as well as the basal interleukin (IL)-1ß protein levels]. Diurnal salivary cortisol curve parameters such as the cortisol awaking response (CAR) and area under the curve (AUCtotal and AUCi) as well as inflammatory and metabolic indices were also determined. RESULTS: T2DM patients exhibited diminished pGR-S211 protein content, increased GRß, decreased basal GILZ and FKBP5 mRNA levels and increased IL-1ß levels. Flattened DEX-induced GILZ and FKBP5 response curves and a flattened salivary cortisol profile characterized T2DM patients. Significant associations of GR measures and saliva cortisol curve parameters with biochemical and clinical characteristics were found. CONCLUSION: Our novel data implicate an insufficient GR signaling in PBMCs in T2DM patients and HPA axis dysfunction. The significant associations of GR-signaling parameters with inflammatory and metabolic indices implicate that GR may be the critical link between HPA axis dysfunction, hypercortisolemia and diabetes-associated metabolic disturbances. Our findings provide significant insights into the contribution of GR-mediated mechanisms in T2DM aetiopathology and therapy.
Subject(s)
Biomarkers/metabolism , Diabetes Mellitus, Type 2/complications , Hydrocortisone/blood , Inflammation/pathology , Metabolic Diseases/pathology , Receptors, Glucocorticoid/metabolism , Saliva/metabolism , Blood Glucose/analysis , Case-Control Studies , Female , Follow-Up Studies , Humans , Inflammation/etiology , Inflammation/metabolism , Male , Metabolic Diseases/etiology , Metabolic Diseases/metabolism , Middle Aged , PrognosisABSTRACT
Current hypertension guidelines advocate strategies encouraging healthy lifestyle behaviours. So far, there is a paucity of studies for the efficacy of such multifaceted programmes. The aim of this study is to investigate the efficacy of an 8-week health-promotion programme for lowering blood pressure (BP) in prehypertensive and hypertensive patients in the community. This was a quasi-experimental study using wait-list controls of 548 patients. The intervention group was administered with an 8-week health-promotion intervention. Measurements included home BP, smoking, body mass index (BMI), perceived stress, depression, anxiety and Health Locus of Control. After adjusting for confounders, the intervention group had a significant reduction in both systolic BP (SBP; mean -2.62 mm Hg, 95% confidence interval (CI): -1.29 to -3.96) and diastolic BP (DBP; mean -1.0, 95% CI: -0.93 to -1.9) compared with controls. In all, 14.9% of patients in the intervention group had >10 mm Hg reduction in SBP vs 4.4% in the control group (P<0.001, numbers needed to treat (NNT)=10). With regards to DBP, 21.7% of patients in the intervention group had >5 mm Hg reduction vs 12.5% in the control group (P=0.01, NNT=11). In terms of effect size, moderate-to-large improvements of BMI, perceived stress, anxiety, depression, external and chance Health Locus of Control were recorded. Changes in SBP and DBP were attributed to BMI and depressive symptom reductions, respectively. Comprehensive non-pharmaceutical programmes for BP management are strongly encouraged. Their long-term benefits on cardiovascular morbidity and mortality remain to be established by future research.
Subject(s)
Health Behavior , Health Promotion/methods , Healthy Lifestyle , Hypertension/therapy , Prehypertension/therapy , Risk Reduction Behavior , Self Care/methods , Stress, Psychological/therapy , Adolescent , Adult , Aged , Female , Greece , Humans , Hypertension/diagnosis , Hypertension/physiopathology , Hypertension/psychology , Male , Middle Aged , Prehypertension/diagnosis , Prehypertension/physiopathology , Prehypertension/psychology , Risk Factors , Stress, Psychological/diagnosis , Stress, Psychological/physiopathology , Stress, Psychological/psychology , Time Factors , Treatment Outcome , Young AdultABSTRACT
Erectile dysfunction (ED) is a complex disorder with various biopsychosocial implications leading the individual into a state of chronic stress that further worsens ED symptoms. The aim of this study is to investigate the effects of a 8-week stress management programme on erectile dysfunction (ED). A convenience sample of 31 newly diagnosed men with ED, aged between 20 and 55 years, was recruited during a period of 5 months to receive either tadalafil (12 patients) or tadalafil and the 8-week stress management programme. Both groups showed statistical significant improvement of both perceived stress and erectile function scores. Men practising stress management showed a statistical significant reduction in perceived stress score compared with men receiving tadalafil alone. No other statistical significant differences were noted between the two groups, although the stress management group showed a lower daily exposure to cortisol compared with the control group after 8 weeks. Finally, perceived stress and cortisol showed some interesting correlations with sexual function measurements. These findings provide important insight into the role of stress management, as part of the recommended biopsychosocial approach, in ED. Future studies should focus on randomised, controlled trials with larger samples and longer follow-up time.
