Differences between nighttime and daytime hypoglycemia counterregulation in healthy humans

Disturbances in hormonal counterregulation may be the main reason why many type 1 diabetic patients are asymptomatic during nighttime hypoglycemia. While it is known that sleep attenuates counterregulatory responses to hypoglycemia, the influence of the time of day on hormonal counterregulation regulation remains obscure. We induced hypoglycemia at 2 different time intervals, ie, in the morning and in the early night, in healthy subjects staying awake throughout the experiments. As compared with the morning hypoglycemia, epinephrine response during early nighttime hypoglycemia was markedly enhanced (P < .001). Baseline corticotropin (ACTH) and cortisol levels were higher in the morning than during nighttime (P < .001 for both). However, the increase of both hormones was stronger at nighttime (P = .045 and P < .001, respectively), so that at the end of the hypoglycemic clamp, levels at nighttime were comparable to morning levels. In the morning, the increase in glucagon levels was more pronounced than during nighttime (P = .019), but given that baseline glucagon levels were distinctly higher at nighttime than in the morning (P = .003), at the end of the clamps, levels of this hormone remained still higher at nighttime than in the morning (P = .017). The increase in growth hormone during hypoglycemia did not differ between morning and nighttime (P = .728). Data shows that several components of hormonal counterregulation against hypoglycemia are influenced by the time of day. Especially, the markedly enhanced epinephrine response to early nighttime hypoglycemia could be clinically important, because this neuroendocrine response is known to play a crucial role in mediating the awareness of and metabolic defensive mechanism against hypoglycemia.