Sequence of events during development of the dawn phenomenon in insulin-dependent diabetes mellitus.

During constant insulin infusion (0.15 mU X kg-1 X min-1) from 12 PM to 8 AM in 10 IDDM patients previously rendered euglycemic (Biostator), plasma glucose (5.4 +/- 0.2 mmol/L at 12 PM) increased by 3:30 AM and reached 12.1 +/- 1.6 mmol/L at 8 AM (P less than 0.001). Glucose production also increased at 3:30 AM; hyperglycemia, glucose utilization did not increase until after 5 AM. Plasma growth hormone (12 PM to 4 AM), cortisol (after 3:30 AM), noradrenaline (after 1:30 AM), and adrenaline (after 3:30 AM) but not glucagon increased significantly overnight, although plasma adrenaline and noradrenaline remained at subthreshold levels. Insulin clearance increased (approximately 25%, P less than 0.05) but only after 7 AM, resulting in a 4 mU/L decrease in plasma insulin. A significant correlation was found between increases in plasma glucose and increases in glucose production (r = 0.74, P less than 0.05) which in turn were significantly correlated with nocturnal peaks in plasma growth hormone (r = 0.66, P less than 0.05). From the sequence of events observed, we conclude that the Dawn Phenomenon in IDDM begins earlier than is currently thought (approximately 3:30 AM), that it is due to both accelerated glucose production and impaired glucose utilization, and that nocturnal increases in sympathetic nervous system activity and/or growth hormone secretion, but not changes in secretion of cortisol, adrenaline and glucagon or changes in insulin clearance, may be of pathogenetic importance.