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.
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.
Pavlatou
Maria G
MG
First Department of Pediatrics, Athens University Medical School, Athens, Greece. pavlatoum@yahoo.gr
Mastorakos
George
G
Lekakis
Ioannis
I
Liatis
Stavros
S
Vamvakou
Georgia
G
Zoumakis
Emmanuel
E
Papassotiriou
Ioannis
I
Rabavilas
Andreas D
AD
Katsilambros
Nikolaos
N
Chrousos
George P
GP
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
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