Restoration of Glucose Homeostasis in Insulin-dependent Diabetic Subjects: An Inducible Process

Abstract

To assess the change in glucose handling capability of diabetic patients regulated with an artificial β-cell, five insulin-dependent diabetic subjects were challenged with a 100-g glucose meal while on conventional (single or split mixed insulin injections) therapy and again after 72 h on an artificial β-cell unit. It was determined that while receiving conventional therapy, the diabetic patient's capacity to oxidize glucose was severely impaired. In addition, glucose storage was markedly reduced. After 72 h on the artificial β-cell unit, the diabetic patient's capacity to oxidize glucose following the ingestion of the glucose meal significantly exceeded that of the control group, and glucose storage returned to normal. Since the above study did not reveal the amount of time on the artificial β-cell required to restore the glucose processing capability of the diabetic patients to normal, their response to a mixed test meal ingested at noon was monitored while they were on conventional insulin therapy and during four consecutive days that they were on the artificial β-cell. This inquiry revealed a gradual increase in their capacity to oxidize carbohydrate in response to the test meal. In contrast, their ability to store carbohydrate was normalized within 24 h following initiation of artificial β-cell therapy. These studies clearly reveal that the conventionally treated diabetic patient's capacity to both oxidize and store carbohydrate is severely impaired. Both functions can be restored to normal by the use of the artificial β-cell for 48–72 h. Most importantly, the gradual improvement in carbohydrate oxidation with respect to the daily mixed meal challenge suggests that it is an “inducible” process which requires at least 2–3 days to accomplish. Since the ability to both oxidize and store incoming carbohydrate is essential for glucose homeostasis, these observations may have significant implications for the care of diabetic patients.