Diabetic neuropathy is associated with increased activity of the hypothalamic-pituitary-adrenal axis

This study has sought to investigate whether diabetic neuropathy is a major determinant of the basal tone of the hypothalamic-pituitary-adrenal axis in diabetes mellitus. We have analyzed the changes in ACTH and cortisol by measuring hourly samples from 0800-1900 h in diabetic patients carefully characterized for the presence of neuropathy. The circadian variation for ACTH and cortisol was normal in these patients. However, integrated secretion (area under the curve) of both ACTH and cortisol was increased specifically in the 25 diabetic patients with symptomatic polyneuropathy (43 +/- 20 pmol/L and 3609 +/- 169 nmol/L, respectively) compared to 19 diabetic patients without neuropathy (30 +/- 10 pmol/L and 2800 +/- 690 nmol/L, respectively) (P < 0.02) and to 11 normal controls (26 +/- 10 pmol/L and 2694 +/- 476 nmol/L, respectively) (P < 0.007). These differences occurred independently of the type of diabetes and were significant for most individual time points. ACTH and cortisol concentrations correlated with most clinical and neurophysiological parameters of neuropathy (P < 0.05-0.001), but not with glycemic control, retinopathy, or proteinuria. Overall, these results suggest that diabetic neuropathy is associated with a specific and persistent increase in the activity of the hypothalamic-pituitary-adrenal axis.