Hypothalamic-pituitary-adrenal activity in type 2 diabetes mellitus: role of autonomic imbalance

Iacopo Chiodini, Sergio Di Lembo, Valentina Morelli, Paolo Epaminonda, Francesca Coletti, Benedetta Masserini, Alfredo Scillitani, Maura Arosio, Guido Adda

Research output: Contribution to journalArticle

Abstract

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 μg/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 μg/dL, P <.05; post-dexamethasone suppression cortisol, 1.2 ± 0.4 vs 0.8 ± 0.6 μg/dL, P <.05, respectively) and group B (UFC, 26.3 ± 11.0 μg/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 (β = -0.40, P = .004) and tended to be associated with the lying-to-standing test (β = -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.

Original languageEnglish
Pages (from-to)1135-1140
Number of pages6
JournalMetabolism
Volume55
Issue number8
DOIs
Publication statusPublished - Aug 2006

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Type 2 Diabetes Mellitus
Hydrocortisone
Hypothalamus
Adrenocorticotropic Hormone
Dexamethasone
Respiration
Orthostatic Hypotension
Cushing Syndrome
Diabetic Neuropathies
Glycosylated Hemoglobin A
Observational Studies
Body Mass Index
Regression Analysis
Serum

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Hypothalamic-pituitary-adrenal activity in type 2 diabetes mellitus : role of autonomic imbalance. / Chiodini, Iacopo; Di Lembo, Sergio; Morelli, Valentina; Epaminonda, Paolo; Coletti, Francesca; Masserini, Benedetta; Scillitani, Alfredo; Arosio, Maura; Adda, Guido.

In: Metabolism, Vol. 55, No. 8, 08.2006, p. 1135-1140.

Research output: Contribution to journalArticle

Chiodini, Iacopo ; Di Lembo, Sergio ; Morelli, Valentina ; Epaminonda, Paolo ; Coletti, Francesca ; Masserini, Benedetta ; Scillitani, Alfredo ; Arosio, Maura ; Adda, Guido. / Hypothalamic-pituitary-adrenal activity in type 2 diabetes mellitus : role of autonomic imbalance. In: Metabolism. 2006 ; Vol. 55, No. 8. pp. 1135-1140.
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AU - Epaminonda, Paolo

AU - Coletti, Francesca

AU - Masserini, Benedetta

AU - Scillitani, Alfredo

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AU - Adda, Guido

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N2 - 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 μg/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 μg/dL, P <.05; post-dexamethasone suppression cortisol, 1.2 ± 0.4 vs 0.8 ± 0.6 μg/dL, P <.05, respectively) and group B (UFC, 26.3 ± 11.0 μg/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 (β = -0.40, P = .004) and tended to be associated with the lying-to-standing test (β = -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.

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