Glycerol Prevents Insulin Precipitation and Interruption of Flow in an Implantable Insulin Infusion Pump

Insulin precipitation is a major obstacle to the use of implantable insulin infusion pumps. In one such pump (Infusaid, Infusaid Corporation, Norwood, Massachusetts), unprotected insulin precipitated and occluded nine pumps implanted in normal dogs within 43 days. In contrast, two similar pumps containing insulin mixed with 80% glycerol functioned normally for more than 250 days. In human studies, a similar mixture allowed insulin to be delivered to nine diabetic subjects for more than 6 mo in each case; total fluid flow rates from the pump were essentially unchanged after 460 patients-weeks of insulin infusion. A possible drawback of the mixture is a time- and temperature-dependent propensity to cause the formation of soluble, higher-molecular-weight insulin polymers, which apparently have lower biologic activity. Formation of such polymers and maintenance of biologic activity were largely prevented by the addition of phosphate buffer at neutral pH.