Hyperactivity of the hypothalamic-pituitary-adrenal axis in patients with type 2 diabetes and relations with insulin resistance and chronic complications.
OBJECTIVE
Connection between abdominal obesity, type 2 diabetes, and the hypothalamic-pituitary-adrenal (HPA) axis activity remains unclear. The aim of this study was to measure HPA axis activity in 121 type 2 diabetics, in 29 obese subjects, and 19 control subjects.


METHODS
Physical examination, anthropometric measures, psychological questionnaire, psychiatric interview, neurological and ophthalmologic examination were performed. Biochemical parameters, urinary free cortisol levels (UFC), cortisol and ACTH levels at 8 and 16 h, cortisol levels after overnight suppression with 1 mg dexamethasone followed by ACTH test in 30 and 60 min were measured. Groups were stratified in relation to obesity, body fat distribution, and chronic complications.


RESULTS
UFC and postdexamethasone cortisol were significantly increased in diabetic patients compared with both obese subjects (p < 0.01) and control group (p < 0.05), regardless to diabetic complications and obesity. Postdexamethasone cortisol was correlated with waist circumference. ACTH-induced cortisol levels were significantly higher in all type 2 diabetic patients. An independent association was found between AUC cortisol in ACTH test and insulin resistance. Multiple regression analysis showed that waist circumference was independently associated with sex, fasting plasma insulin, morning cortisol, and AUC of cortisol in ACTH test (R(2) = 0.334,p < 0.0000).


CONCLUSIONS
In type 2 diabetic patients, the HPA axis is clearly hyperactive as evident in increased urinary free cortisol, diminished cortisol suppression after dexamethasone and increased ACTH-induced cortisol levels. Abdominal obesity and the presence of chronic complications increased the HPA axis hyperactivity in type 2 diabetes. Augmentation of positive feedback is associated with insulin resistance and negative feedback with abdominal obesity.
Department of Internal Medicine, Division of Endocrinology, University Hospital Osijek, Huttlerova 4, 31000 Osijek, Croatia. prpic-krizevac.ivana@kbco.hr
Ivana
I
Prpić-Križevac
Silvija
S
Canecki-Varžić
Ines
I
Bilić-Ćurčić
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D002908:Chronic Disease; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000503:physiopathology*
D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone