Awakening and counterregulatory response to hypoglycemia during early and late sleep

Abstract

Nocturnal hypoglycemia represents an important problem for diabetic patients which has been attributed primarily to an attenuated hormonal counterregulation during sleep. So far hypoglycemia counterregulation has been examined exclusively during the early part of nocturnal sleep, although this markedly differs from late sleep. Here, we investigated whether awakening and counterregulatory responses differ between early and late sleep. Sixteen healthy subjects were tested on 3 different nocturnal conditions. On two nights a linear fall in plasma glucose to a nadir of 2.2 mmol/l within 60min was induced by insulin infusion. On one of the nights this was done after sleep onset as soon as the subject had reached stage 2 sleep (early sleep hypoglycemia), on the other night hypoglycemia was induced after about 3.5 hours of sleep (i.e., ˜3:00h; late sleep hypoglycemia). In a further control night no hypoglycemia was induced. During early sleep, 10 subjects awoke in response to hypoglycemia, while no subject awoke during the corresponding interval of the control night (P < 0.004). During late sleep all 16 subjects awoke upon hypoglycemia, and 4 subjects awoke spontaneously during the control interval (P < 0.001). The pattern indicates that the rate of awakenings caused by hypoglycemia is very similar for early and late sleep, although awakenings occur generally more often during late sleep (P =0.011 for time effect; P <0.001 for hypo effect). In contrast, the increase in most counterregulatory hormones, i.e. epinephrine, norepinephrine, ACTH, cortisol, and growth hormone, was distinctly weaker during the late than early hypoglycemia (all P <0.05). The diminished hormonal counterregulation during late nocturnal sleep could be one factor contributing to the clinically observed accumulation of hypoglycemic episodes in the later part of the night in patients with diabetes.