Relationship between type 2 diabetes mellitus and hypothalamic-pituitary-adrenal axis.

INTRODUCTION

Hypercortisolism often leads to impaired glucose tolerance or type 2 diabetes mellitus. On the other hand, changes in the regulation of hypothalamic-pituitary-adrenal axis become a matter of debate in patients with type 2 diabetes mellitus/metabolic syndrome.

PATIENTS, MATERIALS, AND METHODS: Authors assessed the hypothalamic-pituitary-adrenal axis activity and subclinical Cushing's syndrome occurrence in 50 patients with type 2 diabetes mellitus in comparison to 25 sex-, age-, and BMI-matched control nondiabetic subjects. 1 mg dexamethasone suppression test with NIH recommended cut-off level for adrenal incidentaloma (serum cortisol after suppression > 138 nmol/l) was used to postulate the diagnosis of subclinical hypercortisolism.

RESULTS

There were no significant differences in serum ACTH, DHEA-S, baseline serum cortisol as well as serum cortisol after suppression of 1 mg dexamethasone/subclinical Cushing's syndrome prevalence in both diabetic and control groups (18 vs. 24% respectively, p = 0.54) and there was no relation to the type of treatment (OAD vs. insulin) in group of diabetics. When divided according to age, diabetics older than 60 years suppressed their serum cortisol significantly worse than their age-related controls (99.3 vs. 85.5 nmol/l, p = 0.0001). Furthermore, diabetics did not show an age-related decrease in DHEA-S levels, whereas controls did (r = -0.302, p = 0.033; r = -0.596, p = 0.0017 respectively). Within the group of diabetics, a positive correlation between C-peptide levels and baseline serum cortisol/DHEA-S levels was detected as well (r = 0.445, p = 0.001 and r = 0.339, p = 0.017 respectively).

CONCLUSION

Our data show relatively high but comparable lack of cortisol suppression in both diabetic and control groups; however, we consider the subclinical Cushing's syndrome diagnose to be criteria dependent. There is no dependence of type of diabetes treatment (OAD vs. insulin) on HPA axis activity. Our results might indicate the possible role of cortisol in pathogenesis of type 2 diabetes mellitus in patients with metabolic syndrome as well as possible protective role of DHEA-S within the frame of secondary contraregulatory mechanisms aimed to improve insulin sensitivity and reduce the hyperinsulinemia.