The use of human ultralente is limited by great intraindividual variability in overnight plasma insulin profiles

Our objective was to investigate the usefulness of human ultralente insulin as basal substitution overnight in patients with Type 1 diabetes treated w ith multiple insulin injection therapy by evaluating the free insulin and g lucose profiles, the day-to-day variability and the impact of the time of i njection. Methods: Ten patients with Type 1 diabetes and with good metaboli c control (mean HbAlc 6.0%), treated with regular human insulin before brea kfast, lunch and dinner and human ultralente (Ultratard(R)) before dinner o r at bedtime, were studied. Plasma profiles of blood glucose and free insul in were measured on three occasions from 16.00 h until noon the next day. O n two of these occasions Ultratard(R) was injected before dinner and once i t was injected at bedtime in randomized order. Results: Injection of regula r insulin before dinner resulted in a high insulin peak during the evening but no insulin peak was found that could be attributed to ultralente. The p lasma concentration of free insulin at 03.00 h was 11.0+/-1.9 mU/L and it s lowly decreased to 6.4+/-1.4 at 12.00 h after administration of ultralente at 17.00 h. There were no differences in the mean plasma insulin profiles c ompared to the other occasion when insulin was given at 17.00 h or at 22.00 h. On the other hand, the intra-individual day-to-day variability of mean insulin concentration during the night was considerable, often exceeding 50 %. No differences were noted in the mean blood glucose profiles between the three occasions. Conclusion: Human ultralente insulin gives an insulin pro file suitable for overnight substitution, but the great day-to-day variabil ity limits its usefulness. It can be injected before dinner or at bedtime w ithout any change in the insulin profile during the night.