Increased secretory activity of the hypothalamo-pituitary-adrenocortical (HPA) axis during early night-time sleep in patients with type 1 diabetes

Objectives: Both type 1 and type 2 diabetes mellitus are associated with increased secretory activity of the hypothalamo-pituitary-adrenocortical (HPA) axis which plays an important role in modulating sleep and alertness maintenance. However, HPA secretory activity during sleep has not been assessed in type 1 diabetic patients so far. This was examined in the present experiments.

Methods: 14 patients with type 1 diabetes and 14 healthy control subjects were tested after one adaptation night. Sleep was monitored by polysomnography, and circulating glucose, insulin, ACTH, and cortisol concentrations were measured in 30-min intervals. In the diabetic patients, spontaneous hypoglycemia (<3.86 mmol/l) was carefully avoided by glucose infusion whenever necessary.

Results: During the entire night plasma glucose (P=0.027) and serum insulin (P=0.026) levels were higher in diabetic patients than in healthy control subjects. Total sleep time (TST) did not differ between both groups (404 vs. 395min; P=0.925). However, diabetic patients spent significantly more time in sleep stage 2 than healthy subjects during both the first (60 vs. 46% of total sleep time; P=0.035) and the second (56 vs.43%; P=0.041) half of the night. In addition, diabetic patients tended to spend less time in slow wave sleep during the first half of the night (18 vs. 27%, P=0.093). Plasma ACTH levels were significantly higher (AUC: 1021 vs. 694 pg/ml; P=0.010) and serum cortisol levels tended to be higher (AUC: 463 vs. 270µg/dl; P=0.072) in the diabetic than in the healthy control subjects during the first half of the night, whereas no such differences were observed in the second half of the night (P>0.26).

Conclusions: Data indicate increased HPA secretory activity in type 1 diabetic patients during the first half of night sleep along with a tendency towards lighter sleep. It remains to be elucidated whether the increased HPA axis activity results from impaired sleep quality or vice versa. Also, the role of hyperglycemia and hyperinsulinemia remains to be clarified in this context.