Russell, Steven Jon, PhD
Closed-loop, microdose glucagon administration for the automated prevention and treatment of hypoglycemia
General Research Subject: Both Type 1 And Type 2 Diabetes
Focus: Clinical Therapeutics/New Technology\Glucose Monitoring and Sensing, Clinical Therapeutics/New Technology\Insulin Delivery Systems, Clinical Therapeutics/New Technology\Other Drug Delivery Systems
Type of Grant: ADA-Novo Nordisk Award in Hypoglycemia in Diabetes
Project Start Date: July 1, 2012
Project End Date: June 30, 2015
Diabetes Type: Type 1 diabetes
Good blood sugar control is very important to avoid complication from diabetes, but it is difficult to achieve without low blood sugars (hypoglycemia). One approach to this problem is the development automatic systems that stop the flow of insulin if the blood sugar falls to low, but these won't be able to prevent hypoglycemia, just reduce its severity. We have shown that very low doses of glucagon given automatically by a system that uses a continuous glucose monitor to measure the blood sugar is very effective in preventing hypoglycemia. So far, it has been tested only in a system that also automatically controls the flow of insulin, but that sort of system won't be approved for sale some time. A system that automatically gives glucagon to prevent hypoglycemia could also be used by a person who controls their own insulin, and could be available much sooner.
We plan to do a set of experiments to test the idea, in which volunteers will wear an automatic glucagon dosing system for two weeks. Each day they will fill the system with glucagon or a salt-water solution. Neither the doctors running the trial or the volunteers will know which solution is in the system. A continuous glucose monitor will measure how often the volunteers have low blood sugars and any side-effects on days with or without glucagon. The results of this study will show whether automatic glucagon delivery can reduce hypoglycemia and whether any problems that occur are caused by the glucagon.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
This project addresses the ever-present risk of hypoglycemia (low blood sugar) for people with diabetes who take insulin. We will test a system that estimates the blood sugar every five minutes around the clock using a continuous glucose monitor and automatically gives tiny doses of glucagon through an insulin pump as needed to prevent hypoglycemia. During the study subjects will go about their daily activities and take insulin as usual for two weeks. Each day participants in the study will fill the pump reservoir of the experimental system with either glucagon or a placebo (a solution without any glucagon) from a coded vial. During half of the study days the system will give glucagon and during the other half no glucagon will be given. Neither the participants nor the researchers will know which days are which until the end of the study. At the end of the study the number of episodes of low blood sugar and the amount of time with low blood sugar will be compared between days with glucagon in the system and days with placebo. The results will show whether automatic administration of small doses of glucagon reduces hypoglycemia and to what degree.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
Tight blood sugar control is important to prevent the complications of diabetes, but it is very difficult to achieve. One of the main limiting factors is the risk and fear of hypoglycemia. This project will determine whether automatic administration of glucagon to prevent low blood sugar is effective. If the system is successful in reducing hypoglycemia, it could be developed into a commercial system. A patient might have a pump with two reservoirs, one with insulin and one with glucagon. They would control the dosing of insulin and the glucagon dosing would be automatic, given by the system to protect them from low blood sugar. Because it is automatic, the system would provide additional safety at night and for people who cannot sense when they are low. The automatic system for glucagon dosing is the same as used in a full bionic pancreas that gives both insulin and glucagon, which is currently being tested in volunteers admitted to the hospital. Although the full bionic pancreas system isn't ready for testing at home during normal daily activities, this project will allow us to test the glucagon part of the system. The automatic system for giving glucagon alone might become available before the full bionic pancreas. The results from this project may also suggest ways in which the glucagon part of the full bionic pancreas could be improved, which would make the first generation of that system more effective.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
I became involved in the development of automated systems to improve blood sugar control because I wanted something better for my patients and my friends who either have type 1 diabetes or have children with diabetes. It is my hope that a cure or prevention for type 1 diabetes will be found soon, but in the meantime I believe that automated blood sugar control is the next best thing and can dramatically reduce both the complications of diabetes and the risk of hypoglycemia.
In what direction do you see the future of diabetes research going?
Two major goals of type 1 diabetes research are prevention and/or effective treatment of the autoimmune attack on the insulin producing cells of the pancreas and work towards better management of blood sugar and prevention of complications. Our work falls in the second category. In the near term, I see great progress on the management front, with progressively more automation of blood sugar control leading to far fewer problems associated with hypoglycemia and a much smaller risk of complications than is the case now. In the medium to long term I see the current, early progress on regulating the immune attack on the islets leading to preservation of islet function. Until those therapies are perfected there will likely be a period when they are combined with the bionic pancreas to achieve near normal blood sugar control. Eventually, we'll understand the immune attack well enough and can block it effectively enough that the bionic pancreas won’t be needed in most cases, or will only be needed around the time of diagnosis until the immune therapies have time to work.
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