Awakening and counterregulatory response to hypoglycemia during early and late sleep

Nocturnal hypoglycemia represents an important problem for diabetic patients, which has been primarily attributed to an attenuated hormonal counterregulation during sleep. So far, hypoglycemia counterregulation has been exclusively examined during early nocturnal sleep, although early sleep differs markedly in sleep stage architecture from late sleep. Here, we investigated whether awakening and counterregulatory responses differ between early and late sleep.

Sixteen healthy subjects were tested on three occasions. On two nights, a linear fall in plasma glucose to a nadir of 2.2 mmol/l within 60 min was induced by insulin infusion. On one night, this was done immediately after sleep onset and on the other night after approximately 3.5 h of sleep. In a further control night, no hypoglycemia was induced.

During early sleep, 10 subjects awoke in response to hypoglycemia, whereas no subject awoke during the corresponding interval of the control night (P < 0.004). During late sleep, all subjects awoke upon hypoglycemia, and four subjects awoke spontaneously during the corresponding control interval (P < 0.001). The pattern indicates that the frequency of awakenings caused by hypoglycemia is similar for early and late sleep. Increases in epinephrine, norepinephrine, ACTH, cortisol, and growth hormone were distinctly weaker during late than early hypoglycemia (all P < 0.05).

Diminished hormonal counterregulation during late 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.