Insulin secretion rates after glucose loading were calculated from peripheral venous IRI concentrations considering half life and distribution space of exogenous insulin in normal men and dogs. The coefficients of multiple linear regression analysis between insulin secretion rates and plasma glucose (level and order and rate of change) were used as algorithm parameters in glucose-controlled insulin infusions. These were carried out in each dog based on individual estimations before the induction of diabetes but in the diabetic patients based on values derived from a group of normal subjects. Using this formula, nearly normal patterns of glucose and of insulin were observed in diabetic men and dogs under basal conditions and after IV glucose loading but not after meals. This algorithm enables selection of the parameters prospectively. The effect of a parameter combination depends on insulin sensitivity and it should be appropriately adapted. In the diabetic patients there was no predictable influence of the brittle or stable characteristics of the disease nor of insulin antibodies on the glucose curves obtained with glucose controlled insulin infusions.

The profiles of blood glucose and of insulin dosage were compared between the first and second of 2 consecutive days of Biostator administration under constant conditions in 12 brittle type I diabetic inpatients. All blood glucose criteria and the daily insulin doses were reproducible between these 2 days for the entire group of patients. In nearly all patients, however, there were distinct but unsystematic differences between the 2 days in the diurnal patterns of insulin dose distribution. These differences could be ascribed to some stress reaction or inherent metabolic lability. It is concluded that, in these extremely labile diabetic patients, due to the insufficient short-term reproducibility of the outcome of an extracorporal artificial beta-cell, caution must be used when constant profiles are to be predicted from these doses for open-loop insulin delivery systems or for conventional subcutaneous injection therapy.

In 92 particularly unstable IDDM patients we have tried to avoid any gap in daily insulin supply by applying one out of four newly designed combinations of regular and depot insulin. The short-term effect after three weeks and the long-term effect after greater than or equal to 12 months (data from 30 patients only) of these new regimens were compared with those of the traditional regimen in a retrospective evaluation: Glycemia (level and excursions) was significantly improved both after three weeks of inpatient treatment and after greater than or equal to 12 additional months on outpatient regimen. Serum beta-LP and HbA1 showed slight decrease during long-term follow-up. The majority of the patients reported improved well-being under conditions of daily life. However, the glycemia achieved was still far from the permanent euglycemia aimed at. For the avoidance of any gap in insulin supply in labile diabetics four insulin injections are necessary in most cases. For this, individually tailored combinations of regular and depot insulin must be drawn up carefully together with the patients to avoid a " strait -jacket" system which would not work under conditions of daily life.

Twenty unselected unstable type I diabetic inpatients whose blood glucose control was insufficient employing three daily s.c. injections of regular insulin supplemented by intermediate acting insulin were subjected to a 48-hour treatment with the Biostator -GCIIS when both diet and muscular exercise were kept as close as possible to the conditions at home. The s.c. injection regimen was adjusted to the insulin dose pattern required by the artificial beta cell. There was significant metabolic improvement in 16 out of the 20 patients on discharge, in comparison to the pre-Biostator conditions. This improvement was still present when the patients were re-admitted after an average of seven months. It is concluded that in certain cases of unstable type I diabetes mellitus the metabolic re-arrangement based on intercalary days on an extracorporal artificial beta cell might be useful if the control constants are adapted to minimize the insulin requirement by the machine.