OBJECTIVE: The purpose of this study was to assess the efficacy of an insulin priming dose with a continuous insulin infusion versus two continuous infusions without a priming dose. RESEARCH DESIGN AND METHODS: This prospective randomized protocol used three insulin therapy methods: 1) load group using a priming dose of 0.07 units of regular insulin per kg body weight followed by a dose of 0.07 unit x kg(-1) x h(-1) i.v. in 12 patients with diabetic ketoacidosis (DKA); 2) no load group using an infusion of regular insulin of 0.07 unit . kg body weight(-1) x h(-1) without a loading dose in 12 patients with DKA, and 3) twice no load group using an infusion of regular insulin of 0.14 x kg(-1) x h(-1) without a loading dose in 13 patients with DKA. Outcome was based on the effects of insulin therapy on biochemical and hormonal changes during treatment and recovery of DKA. RESULTS: The load group reached a peak in free insulin value (460 microU/ml) within 5 min and plateaued at 88 microU/ml in 60 min. The twice no load group reached a peak (200 microU/ml) at 45 min. The no load group reached a peak (60 microU/ml) in 60-120 min. Five patients in the no load group required supplemental insulin doses to decrease initial glucose levels by 10%; patients in the twice no load and load groups did not. Except for these differences, times to reach glucose <or=250 mg/dl, pH >or=7.3, and HCO(3)(-) >or=15 mEq/l did not differ significantly among the three groups. CONCLUSIONS: A priming dose in low-dose insulin therapy in patients with DKA is unnecessary if an adequate dose of regular insulin of 0.14 unit x kg body weight(-1) x h(-1) (about 10 units/h in a 70-kg patient) is given.