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The objective of this study was to follow the development of microalbuminuria and nerve conduction velocity under continuous i.v. insulin therapy over a limited period of 4 months. For this purpose, 8 labile type I diabetics were selected (age 33 +/- 8 years, duration of diabetes 16 +/- 9 years) and treated conventionally with two insulin injections daily over 4 months. Afterwards, the same patients were treated with continuous i.v. insulin infusion and finally again with two injections daily over 4 months each. This procedure allowed each diabetic to serve as his own control. HbA1, microalbuminuria, nerve conduction velocity and relative refractory period of the ulnar nerve were checked at monthly intervals. During the continuous i.v. infusion over 4 months, blood sugar values were significantly lower, glucosuria had disappeared almost completely and the glycosylated hemoglobin had fallen to near normal values. The mean rate of albumin excretion was 16 +/- 5 micrograms/min at rest and 76 +/- 26 micrograms/min during exercise (normal: 3.9 +/- 0.4 and 4.8 +/- 1.2 microgram/min, respectively) and did not change significantly. Nerve conduction velocity in the ulnar nerve rose significantly under i.v. insulin therapy from 47.9 +/- 0.6 m/sec to 52 +/- 0.6 m/sec. Similarly, the relative refractory period of the same nerve fell significantly from 3.7 +/- 0.2 to 1.9 +/- 0.1 msec (i.e. to within normal range). It is concluded that functional disturbances of peripheral nerve can regress by improved blood sugar control with continuous i.v. insulin infusion over 4 months. On the other hand, incipient microangiopathy measured as microalbuminuria remains unchanged over the same period of time. If an improvement is at all possible, considerably longer periods of euglycemia are likely to be necessary.

In view of the importance of knowing exactly how much insulin is required by diabetics who are difficult to control with subcutaneous insulin, an insulin infusion program has been tried in such patients. The apparatus, which was produced by Siemens as a prototype, works according to the following simple and flexible principle: During the day a basal rate of insulin is continuously infused. During the three main meals an additional rectangular insulin infusion is initiated by turning a knob. After an hour the apparatus switches automatically back to the basal ratio. We have used this machine in 13 patients who are fully mobile. 11 of them showed an almost ideal blood sugar profile after 4 days. After switching back to subcutaneous insulin 8 of these 11 patients did better than before but not as well as on the insulin infusion program.

11 labile diabetics were well controlled after 2 days of an i.v., open-loop insulin infusion program consisting of constant, empirically determined, basal infusion rates (mean: 1.1 U/h) and superimposed rectangular one-hour insulin infusions between 2 and 8 U/h during the main meals. The steering unit switches automatically back to the basal infusion rate after one hour. An almost optimal blood sugar profile was already obtained on the third day of the infusion program. We believe that such a flexible, open-loop insulin infusion program would render long-term optimal blood sugar control in "labile" diabetics possible if the technological development ever allows implantation of the infusion pumps.