Studies on the pathogenesis of the dawn phenomenon in insulin-dependent diabetic patients

To assess the role of hormonal factors in the pathogenesis of the dawn phenomenon, nocturnal (9:00 PM to 9 AM) concentrations of blood glucose, free insulin, and counterregulatory hormones were determined in eight insulin-dependent diabetic patients under feedback-controlled and continuous insulin infusions after previous blood glucose normalization. Under feedback control, mean insulin requirements, necessary for maintenance of euglycemia rose significantly in the early morning (11:00 PM to 3 AM: 8.4 +/- 1.4; 5 AM to 9 AM: 12.6 +/- 1.5 mU/kg/h; P less than 0.01). Mean free-insulin concentrations did not increase simultaneously. Correspondingly, mean insulin-clearance rates under continuous insulin infusion were higher in the morning (11:00 AM to 3 AM: 359 +/- 58; 5 AM to 9 AM: 459 +/- 72 mL/min/m2; P less than 0.05). Increases of insulin clearance rates were most marked (greater than 15%) in patients whose blood glucose rose during continuous insulin administration. Glucagon and norepinephrine concentrations were stable throughout both parts of the study. Cortisol and growth hormone exhibited the known nocturnal rhythms. Epinephrine levels were at the lower limit of detection at night and rose to normal basal concentrations at 9:00 AM. We conclude that increases of insulin clearance rates may be an important factor for the development of the dawn phenomenon while the role of most counter-regulatory hormones is still uncertain.