title: Blunted glucocorticoid and mineralocorticoid sensitivity to stress in people with diabetes.
abstract: Psychological stress may contribute to type 2 diabetes but mechanisms are still poorly understood. In this study, we examined whether stress responsiveness is associated with glucocorticoid and mineralocorticoid sensitivity in a controlled experimental comparison of people with type 2 diabetes and non-diabetic participants. Thirty-seven diabetes patients and 37 healthy controls underwent psychophysiological stress testing. Glucocorticoid (GR) and mineralocorticoid sensitivity (MR) sensitivity were measured by dexamethasone- and prednisolone-inhibition of lipopolysaccharide (LPS)-induced interleukin (IL) 6 levels, respectively. Blood pressure (BP) and heart rate were monitored continuously, and we periodically assessed salivary cortisol, plasma IL-6 and monocyte chemotactic protein (MCP-1). Following stress, both glucocorticoid and mineralocorticoid sensitivity decreased among healthy controls, but did not change in people with diabetes. There was a main effect of group on dexamethasone (F(1,74)=6.852, p=0.013) and prednisolone (F(1,74)=7.295, p=0.010) sensitivity following stress at 45 min after tasks. People with diabetes showed blunted stress responsivity in systolic BP, diastolic BP, heart rate, IL-6, MCP-1, and impaired post-stress recovery in heart rate. People with Diabetes had higher cortisol levels as measured by the total amount excreted over the day and increased glucocorticoid sensitivity at baseline. Our study suggests that impaired stress responsivity in type-2 diabetes is in part due to a lack of stress-induced changes in mineralocorticoid and glucocorticoid sensitivity.
authors.affiliation: Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, Rm356a, London WC1E 6BR, UK. Electronic address: livia.a.carvalho@ucl.ac.uk.
authors.forename: Livia A
authors.initials: LA
authors.lastname: Carvalho
authors.affiliation: Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, Rm356a, London WC1E 6BR, UK.
authors.forename: Livia
authors.initials: L
authors.lastname: Urbanova
authors.affiliation: Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, Rm356a, London WC1E 6BR, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Hamer
authors.affiliation: Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, Rm356a, London WC1E 6BR, UK.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Hackett
authors.affiliation: Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, Rm356a, London WC1E 6BR, UK.
authors.forename: Antonio I
authors.initials: AI
authors.lastname: Lazzarino
authors.affiliation: Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, Rm356a, London WC1E 6BR, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Steptoe
mesh_terms: D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D018932:Chemokine CCL2 / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000503:physiopathology; D011239:Prednisolone / Q000494:pharmacology; D012463:Saliva / Q000737:chemistry; D013315:Stress, Psychological / Q000097:blood / Q000503:physiopathology*
chemical_list: D018932:Chemokine CCL2; D005938:Glucocorticoids; D015850:Interleukin-6; D003907:Dexamethasone; D011239:Prednisolone; D006854:Hydrocortisone
keywords: Acute stress; Auto-immune diseases; Cardiovascular; Corticosteroid sensitivity; Cytokines; HPA axis