The cycle of frequent hypoglycemia, illustrating the impact of impaired counterregulation that exists in diabetes. Sleep, with reduced cognition and sympathetic output, and other behavioral factors contribute. Frequent hypoglycemic episodes, whether daytime or nighttime, can lead to impaired sympathoadrenal responses, symptom loss, and hypoglycemia unawareness, and eventually, may lead to severe hypoglycemia. Figure adapted from Fanelli et al.[16] Copyright John Wiley & Sons Limited. Reproduced with permission.