The ovine corticotropin-releasing hormone-stimulation test in type I diabetic patients and controls: Suggestion of mild chronic hypercortisolism

Type 1 diabetes mellitus and major depressive disorder: evidence for a biological link

“…Diabetes is associated with a hypercortisolaemic state, characterised by elevated levels of circulating cortisol and increased 24 h levels of urinary free cortisol [84]. Disrupted control of adrenocorticotropic hormone (ACTH) release from pituitary corticotrophs and direct stimulation of corticotropin-releasing hormone of the adrenal gland with or without the release of ACTH leads to hyperactivation of the HPA in patients with diabetes [85]. Furthermore, the impairment of glucocorticoid-negative feedback sensitivity in patients with diabetes also results in increased activity of the HPA axis: following glucocorticoid administration, these patients exhibit a greater incidence of nonsuppression of pituitary-adrenal activity compared with non-diabetic individuals (43% vs 7%, respectively; p<0.01) [86].…”

High glucose activates pituitary proopiomelanocortin gene expression: possible role of free radical‐sensitive transcription factors

“…Indeed, plasma ACTH and cortisol levels are elevated in patients with untreated diabetes mellitus, suggesting that hyperglycemia is a metabolic stress [1][2][3]. Animal experiments using a diabetic rat model support the observation as well [4][5][6].…”

“…Roy et al reported the increase in plasma ACTH and plasma and urinary cortisol in diabetic patients [1][2][3]. In vivo experiments using the type 2 diabetic rat model showed similar effects [4][5][6], and Schwartz et al found a decrease in hypothalamic CRH expression despite the increase in ACTH and cortisol, suggesting the existence of unknown factor(s) stimulating the HPA axis at the pituitary level during high blood glucose [5].…”

Organization and Integration of the Endocrine System: The Arousal and Sleep Perspective

“…[91][92][93][94][95] Because increased gluconeogenesis is a characteristic feature of the stress response1,2 and glucocorticoids induce insulin resistance, [96] activation of the HPA axis may contribute to the poor control of diabetic patients with emotional stress or concurrent inflammatory and other disease. Indeed, mild, chronic activation of the HPA axis was recently demonstrated in patients with type 1 diabetes under moderate or poor glycemic control [97] and in patients with type 2 disease who had developed diabetic neuropathy. [98] Glucocorticoid-induced progressively increasing visceral adiposity directly causes further insulin resistance and deterioration of glycemic control of diabetes mellitus.…”

“…In addition to melancholic depression, a spectrum of other conditions may be associated with increased and prolonged activation of the HPA axis; these include anorexia nervosa and malnutrition, [135][136][137] obsessive-compulsive disorder, [138] panic anxiety, [139] excessive exercise, [72] chronic active alcoholism, [140] alcohol and narcotic withdrawal, [141,142] diabetes mellitus types 1 and [2,97,98] central (visceral) obesity, [92][93][94] childhood sexual abuse, [143] and, perhaps, hyperthyroidism [144] and the premenstrual tension syndrome. [145] It is of interest that anorexia nervosa and malnutrition are characterized by increased levels of cerebrospinal fluid NPY, which, together with the markedly decreased leptin levels, could provide an explanation why the HPA axis in these subjects is activated while the LC/NEsympathetic system shows clear evidence of profound hypoactivity.…”