Use of Pramlintide in Artificial Pancreas Systems May Improve T1D Glucose Control at Mealtimes

Artificial pancreas systems will enable people with T1D to achieve tighter blood glucose control avoiding both highs and dangerous lows, thereby significantly reducing the risk of the disease’s devastating complications. Artificial Pancreas researchers using insulin-only approaches observe that blood glucose levels often overshoot target levels because of the delay in insulin absorption when delivered subcutaneously. Dr. Stuart Weinzimer and his group at Yale University hypothesized that pramlintide, a synthetic form of the natural beta cell hormone amylin that delays stomach emptying and consequently delays the rise of blood glucose after eating as well as suppresses glucagon production in the pancreas, would improve blood glucose control at mealtimes by allowing insulin to keep up with the rate at which glucose from a meal appears in the blood. The group studied eight people with T1D over two days on a closed-loop artificial pancreas system in the hospital setting. No insulin boluses were given before meals. The researchers measured the rise in blood sugar from the beginning of the meal to the highest reading with and without premeal injections of pramlintide. Those who received pramlintide injections were found to have a significantly slower time to reach maximum blood glucose levels and the extent of the blood glucose increases was significantly reduced compared to no pramlintide injection. The group found that pramlintide’s effects on blood sugar increases were particularly evident at lunch and dinner, in association with higher premeal insulin concentrations at those mealtimes compared with at breakfast.

Ramifications for Individuals with T1D:

While more research is needed, these results suggest that pramlintide can delay the appearance of glucose in the blood after a meal and its use may be a feasible approach to improve glucose control in an artificial pancreas system. While these studies evaluated manual injections at mealtimes this method of delivery would reduce the convenience anticipated from a closed loop system. Consequently, if these studies continue to show significant promise it will be important to identify strategies to incorporate pramlintide into an artificial pancreas system using dual chambered pump delivery, co-formulation, or delayed release preparations.

JDRF Involvement:

JDRF partially funded this research through a grant to Dr. Stuart Weinzimer at Yale University. Dr. Weinzimer is a member of the JDRF Artificial Pancreas Consortium.

Investigators and Institutions:

Weinzimer SA, Sherr JL, Cengiz E, Kim G, Ruiz JL, Carria L, Voskanyan G, Roy A, Tamborlane WV.
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA. stuart.weinzimer@yale.edu

Reference:

Weinzimer SA, Sherr JL, Cengiz E, Kim G, Ruiz JL, Carria L, Voskanyan G, Roy A, Tamborlane WV. 2012. Effect of pramlintide on prandial glycemic excursions during closed-loop control in adolescents and young adults with type 1 diabetes. Diabetes Care 35(10):1994-9.