Insulin Dose and Metabolic Regulation

The primary efficacy end-point was the total daily dose of insulin required to achieve euglycemia, which was defined as a daily mean pre-prandial blood glucose concentration of ≤ 7.8 mmol/L (140 mg/dL). The secondary efficacy end-points including EE and RQ, as measured by indirect calorimetry performed one day before treatment day, day 7 and after 12 weeks. Oxygen consumption and carbon dioxide production were measured to calculate the EE and RQ. According to the Weir equation, EE was calculated without using urinary urea nitrogen levels [14 (link)]. Protein oxidation was determined from 24-h urinary nitrogen excretion, and the carbohydrate and lipid oxidation rates were determined from the non-protein RQ. EE and RQ were assessed at the steady state, which was defined as the 10-min time period during which the average minute-by-minute changes in oxygen consumption and carbon dioxide production were < 10% and the average RQ change was < 5% [16 (link)]. The average RQ and EE at the steady state were measured at each 10-min recording period.
The exploratory end-points included the changes in daily urinary glucose excretion, 3β-hydroxybutyrate, acetoacetate concentrations, body weight, systolic blood pressure, and diastolic blood pressure.