title: Chronic administration of an angiotensin II receptor antagonist resets the hypothalamic-pituitary-adrenal (HPA) axis and improves the affect of patients with diabetes mellitus type 2: preliminary results.
abstract: Diabetes mellitus type 2 (DM type 2) is associated with depressive symptomatology and intermittent hyperfunction of the hypothalamic-pituitary-adrenal (HPA) axis. DM type 2 is also accompanied by increased tissue levels of angiotensin II (Ang II), which stimulates the HPA axis through the Ang II type 1 receptors (AT1). We investigated the effect of candesartan, an angiotensin receptor blocker (ARB) that crosses the blood brain barrier, on the activity of the HPA axis and on the affect of 17 patients with DM type 2, aged 40-65 years, who were treated with 4 mg/day candesartan per os for at least 3 months. Before and after candesartan administration, a corticotropin-releasing hormone (CRH) stimulation test and psychological tests were performed. In response to hCRH, time-integrated secretion of ACTH was not altered by candesartan administration, however, the cortisol response was decreased significantly compared to baseline (mean +/- SEM, 2327 +/- 148.3 vs. 1943 +/- 131.9 microg/dl, P = 0.005) suggesting reduced sensitivity of the adrenals to ACTH. In parallel, there was a significant improvement in interpersonal sensitivity (0.91 +/- 0.16 vs. 0.70 +/- 0.15, P = 0.027) and depression scores (0.96 +/- 0.15 vs. 0.71 +/- 0.10, P = 0.026). We suggest that candesartan resets the HPA axis of patients with DM type 2 and improves their affect.
authors.affiliation: First Department of Pediatrics, Athens University Medical School, Athens, Greece. pavlatoum@yahoo.gr
authors.forename: Maria G
authors.initials: MG
authors.lastname: Pavlatou
authors.forename: George
authors.initials: G
authors.lastname: Mastorakos
authors.forename: Ioannis
authors.initials: I
authors.lastname: Lekakis
authors.forename: Stavros
authors.initials: S
authors.lastname: Liatis
authors.forename: Georgia
authors.initials: G
authors.lastname: Vamvakou
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Zoumakis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papassotiriou
authors.forename: Andreas D
authors.initials: AD
authors.lastname: Rabavilas
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Katsilambros
authors.forename: George P
authors.initials: GP
authors.lastname: Chrousos
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000339:Affect / Q000187:drug effects*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000378:metabolism; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000378:metabolism; D001713:Biphenyl Compounds; D001812:Blood-Brain Barrier / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010912:Pituitary-Adrenal Function Tests; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D011569:Psychiatric Status Rating Scales; D013777:Tetrazoles / Q000008:administration & dosage* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; C081643:candesartan; D006854:Hydrocortisone