Acceleration of Insulin Action by Hyaluronidase During Closed-Loop Therapy

To investigate the effect of rHuPH20, an adjuvant that accelerates the dispersion and absorption of subcutaneously injected or infused drugs, on mitigating post-prandial blood glucose excursions when injected separately or co-formulated with insulin during closed-loop therapy for youth and young adults with type 1 diabetes. Closed-loop control will be achieved using external subcutaneous real-time continuous glucose monitoring and continuous subcutaneous insulin infusion along with a computerized algorithm to link these two processes. Specific Aim 1: To examine whether co-formulation rHuPH20 with analog insulin (INS-PH20)or, alternately, pre-administration of rHuPH20 (PH20-preRx) at the time of infusion set placement prior to initiation of closed-loop (CL) insulin delivery will reduce peak-postprandial glucose concentrations and total glucose area under the curve of the meal excursions in short term inpatient experiments. Specific Aim 2: To investigate whether accelerated insulin absorption by rHuPH20, delivered as described above, will also result in a reduction of late-post-prandial hyperinsulinemia and late post-prandial hypoglycemia during CL insulin delivery. Specific Aim 3: To compare the insulin accelerator effect of INS-PH20 to that of PH20-preRx, based on post prandial glucose excursions during closed-loop therapy We hypothesize that; utilization of PH20 either as a separate injection (PH20-preRx) or in a co-formulation with insulin (INS-PH20) during CL therapy will reduce peak-postprandial glucose concentrations and total glucose under the curve of the meal excursion as compared to CL control without any intervention, and we propose that the use of PH20-preRx and INS-PH20 will be well tolerated when delivered in youth and young adults in a closed-loop setting.