Pathogenesis and prevention of the dawn phenomenon in diabetic patients treated with CSII

The mechanism of the dawn phenomenon was studied in 12 C-peptide-negative type I diabetic patients (age 30 +/- 2 yr) treated with continuous subcutaneous insulin infusion. During constant basal infusion, nocturnal glycemia remained constant until 4 a.m., but began to rise thereafter in 10/12 patients, with the mean rise from 4.6 +/- 0.4 mmol/L to 6.1 +/- 0.7 mmol/L (P less than 0.01) by 8 a.m. In these patients the rate of glucose production (Ra, 2.14 +/- 0.04 mg/kg/min, 3-H3-glucose infusion) exceeded the rate of utilization (Rd, 1.89 +/- 0.03 mg/kg/min, P less than 0.02). When the patients were restudied after the infusion rate was increased by 49 +/- 7%, Ra fell to 1.75 +/- 0.03 mg/kg/min (P less than 0.01) and the dawn phenomenon was abolished. However, both Ra and Rd remained higher in the diabetic subjects (P less than 0.05) than in eight healthy control subjects, in whom Ra (1.66 +/- 0.02 mg/kg/min) was equal to Rd with glycemia remaining unchanged. Peripheral free insulin levels in the diabetic patients were similar during constant (12.3 +/- 0.5 mU/L) and increased infusion rate (11.3 +/- 0.4 mU/L), and higher than those of the control subjects (5.2 +/- 0.2 mU/L, P less than 0.05). A diurnal rise in serum cortisol levels occurred 1 h earlier in the diabetic than in the control subjects, and Ra was directly proportional to serum cortisol concentration (r = 0.61, P less than 0.01). Serum growth hormone levels were also slightly higher in the diabetic than the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)