Remission of diabetes was attempted in 12 recent acute onset ketosis-prone juvenile diabetes after short term (5 +/- 1 days) but excellent blood glucose control by the external artificial beta-cell. The comparison group comrised patients undergoing traditional treatment (n = 28). Nine (75%) persistent (over 3-14 months of duration) although partial (oral drugs required) remissions were obtained in the former group as compared to 3 (11%) in the latter group (p less than 0.05). Cases which showed remissions after insulin infusion had a plasma insulin response to IV glucagon still present before insulin infusion, and a daily urinary C-peptide excretion significantly enhanced after (p less than 0.01). Urinary C-peptide/blood glucose remained improved during the remission period. Thus, early effective treatment by means of the artificial pancreas may break the vicious circle hyperglycaemia-insulin depletion-hyperglycaemia and lead to frequent and sustained remissions of juvenile diabetes.

With the artificial pancreas used by the authors, insulin was delivered through a venous infusion and the rate of delivery was adjusted according to data provided by a continuous blood glucose monitor. After different trials we selected control algorithms integrating two parameters: instantaneous blood glucose concentration and increasing or decreasing patterns of blood glucose. A constant basal insulin infusion rate was added and improved the control of glycaemic excursions. Different parameters concerning exogenous insulin homoeostasis were determined. The delay to reach an insulin effect was 18+/-2 min and was shortened by a priming-dose at the beginning of the infusion. The insulin effect remained for 28+/-2 min after the infusion had been stopped, but differences were noted in the morning (21+/-2 min), in the afternoon (32+/-2 min) and during the night (25+/-3 min). Insulin needs were evaluated during meals. Related to the amount of carbohydrates, the doses fell from 0.53 units/hr/g of carbohydrate for breakfast to 0.15 for dinner. From these data, it appears that the efficiency of exogenous insulin exhibits a circadian rhythm.

This work compares different routes of insulin infusion via portable pumps with chronically implanted catheters and evaluates the long-term feasibility of the technique. Six severely unstable (i.e., uncontrolled by optimized intensive insulin therapy) diabetic individuals (age range: 35 +/- 4 yr; duration: 11 +/- 2 yr) were selected. Promedos pumps (Siemens A. G., Erlangen, West Germany) were exclusively used because of their portability and long-life insulin reservoir (1-mo duration with U40 acidic Hoechst insulin). Each patient underwent three randomized 1-mo periods of insulin infusion: subcutaneous (s.c.), intravenous (i.v.), and intraperitoneal (i.p.) before the catheter was left indefinitely in one of these sites. Diabetic control was improved and insulin doses reduced whatever the route of infusion, although the s.c. route gave slightly higher values. These results did not deteriorate with time: mean blood glucose was 126 +/- 3 mg/dl and HbA1 was 8.3 +/- 0.6% after 10-18 mo of constant infusion versus 237 +/- 35 mg/dl and 10.0 +/- 0.8%, respectively, under conventional therapy. From a practical point of view, the i.p. route seems preferable since all s.c. catheters provoked local reactions after less than 1 mo and the two chronic i.v. catheters obstructed after 8 and 9 mo. All other incidents were minor and curable without removal of the catheters. All patients argued improvement of both diabetes and quality of life and no one has resigned so far. Thus, the i.p. infusion technique seems beneficial to unstable diabetic individuals and adaptable to long-term therapy, although intensive education and careful follow-up are necessary.

Circulating lymphocytes from 39 juvenile insulin dependent diabetics of recent onset were studied by six membrane marker techniques and mitogen stimulation. Well controlled (n = 14) were grouped separately from poorly controlled (n = 25) patients. The total lymphocyte counts were not different from 50 control subjects. The percentage of T-cells detected by erythrocyte rosettes and B-cells detected by erythrocytes--antibody--complement rosettes was significantly decreased only in poorly-controlled diabetics (64.1 +/- 1.3 and 9.7 +/- 1.8, vs 71.0 +/- 1.0 and 15.3 +/- 0.6 in controls). Cells bearing receptors for the Fc fragment of IgG immunoglobulins were decreased in both groups. Mitogen stimulation was not different from controls but was significantly lower in poorly controlled than in well controlled diabetics. Optimal blood glucose control for 5 +/- 2 days using an external artificial pancreas led to a rapid normalisation of membrane marker values and mitogen responsiveness of lymphocytes from previously poorly controlled diabetics. Separate in vitro experiments showed that glucose had an inhibitory effect on mitogen stimulation at concentrations greater than or equal to 8.3 mmol/l and on T- and B-lymphocyte numbers at concentrations greater than or equal to 55.6 mmol/l. DL 3-hydroxybutyrate tested at 17.1 and 34.2 mmol/l only depressed mitogen responsiveness. Such results suggest a rapidly reversible T-cell defect closely linked to the existing metabolic disturbances.

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