Hypothalamic-pituitary-adrenal activity in type 2 diabetes mellitus: role of autonomic imbalance.
Symptomatic diabetic neuropathy has been found to be associated with hypothalamus-pituitary-adrenal (HPA) axis hyperfunction, but no data are available about HPA activity in diabetic patients with asymptomatic autonomic imbalance. To evaluate HPA axis activity in patients with type 2 diabetes mellitus (T2DM) in relation to the presence or the absence of subclinical parasympathetic or sympathetic neuronal dysfunction, we performed an observational study on 59 consecutive type 2 diabetic patients without chronic complications and/or symptoms of neuropathy or hypercortisolism. The following were measured: serum cortisol at 08:00 am and at midnight (F8 and F24, respectively), post-dexamethasone suppression cortisol, 24-hour urinary free cortisol (UFC), and morning corticotropin (ACTH). Deep-breathing (DB) and LS (LS) autonomic tests were performed to assess the parasympathetic function; postural hypotension test was performed to evaluate sympathetic activity. Patients were subdivided into 4 groups: subjects with parasympathetic failure (group A), sympathetic failure (group B), both para- and sympathetic failure (group C), and without autonomic failure (group D). Hypothalamus-pituitary-adrenal activity was increased in group A compared with group D (UFC, 48.6 +/- 21.4 vs 21.6 +/- 9.8 microg/24 h, P < .0001; ACTH, 27.0 +/- 8.6 vs 15.7 +/- 5.7 pg/dL, P < .01; F8, 20.4 +/- 4.5 vs 13.6 +/- 3.8 microg/dL, P < .05; post-dexamethasone suppression cortisol, 1.2 +/- 0.4 vs 0.8 +/- 0.6 microg/dL, P < .05, respectively) and group B (UFC, 26.3 +/- 11.0 microg/24 h, P < .0001; ACTH, 19.9 +/- 8.0 pg/dL, P < .05). Regression analysis showed that UFC levels were significantly associated with the deep-breathing test (beta = -0.40, P = .004) and tended to be associated with the lying-to-standing test (beta = -0.26, P = .065), whereas body mass index, glycated hemoglobin, and duration of disease were not. Type 2 diabetic patients with asymptomatic parasympathetic derangement have increased activity of HPA axis, related to the degree of the neuronal dysfunction.
Chiodini
Iacopo
I
Department of Endocrinology, San Giuseppe-Fatebenefratelli Hospital, A.Fa.R., 20123 Milan, Italy. ichiodini@katamail.com
Di Lembo
Sergio
S
Morelli
Valentina
V
Epaminonda
Paolo
P
Coletti
Francesca
F
Masserini
Benedetta
B
Scillitani
Alfredo
A
Arosio
Maura
M
Adda
Guido
G
D000305:Adrenal Cortex Hormones / Q000097:blood; D000328:Adult; D000368:Aged; D001342:Autonomic Nervous System Diseases / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D003907:Dexamethasone; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007024:Hypotension, Orthostatic / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010907:Pituitary Hormones / Q000097:blood; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D012129:Respiratory Function Tests
D000305:Adrenal Cortex Hormones; D010907:Pituitary Hormones; D003907:Dexamethasone; D006854:Hydrocortisone