Abstract
The ultimate goal of artificial beta cell systems is to control the patients' blood glucose over long periods of time. In view of the difficulties encountered in the development of a portable glucose sensor, a small (15×12×5 cm) and light (700 g) Pre-Programmable Insulin Infusion System was devised for long-term clinical use and applied to 7 diabetics who had to begin insulin therapy. With this system, a microcomputer could memorize the duration and rate of insulin infusion for 24 hr which were obtained by using our bedside-type artificial beta cell. The plasma glucose, immunoreactive insulin (IRI), immunoreactive glucagon (IRG) and immunoreactive Cpeptide response (CPR) to iv insulin by the system were compared in each patient with sc regular insulin given 3 times a day, or with sc intermediate-acting insulin injection once a day on 3 consecutive days. In each patient, the insulin dose per day was set to be the same.
The intravenous insulin provided by the system produced adequate homeostasis and IRI responses, which were almost identical to those of normal subjects. With sc intermediate-acting insulin injection (mean dose, 0.66 U/kg/day), the. IRI profile was monophasic and the IRI peak was found to be only 35μU/ml, indicating that this administration method supplemented only the basic insulin secretion, and marked postprandial hyperglycemia was noted. Although with sc regular insulin injections 3 times a day both the M value by Schlichtkrull and the MAGE index by Service were almost the same as in iv insulin infusion by the system, the number of hypoglycemic episodes amounted to 7 times in 7 patients.
The IRG levels tended to be lower when the plasma glucose response and IRI were normalized by the system than when insulin was injected subcutaneously.
In all 7 patients whose CPR was elevated when the plasma glucose concentration was high with sc intermediate-acting insulin injection, the CPR was kept in the lowest concentration during iv insulin infusion, indicating that the beta cell function was maintained in a resting state.
Thus, as an alternative to the artificial beta cell alone, a combination of an artificial beta cell with a Pre-Programmable Insulin Infusion System was shown to be capable of restoring the circadian blood glucose profiles of diabetics to within the physiological range. This combination is thought to be useful for the long-term treatment of ambulant diabetic patients.
