Seaquist, Elizabeth Rachel, MD
Hypoglycemia unawareness in patients with type 1 diabetes: pilot study of naltrexone therapy
General Research Subject: Type 1 Diabetes
Focus: Clinical Therapeutics/New Technology\Pharmacologic Treatment of Diabetes or its Complications, Complications\Hypoglycemia, Complications\Neuropathy
Type of Grant: Distinguished Clinical Scientist
Project Start Date: July 1, 2009
Project End Date: June 30, 2013
Hypoglycemia unawareness is a serious consequence of recurrent hypoglycemia that causes patients to lose their ability to detect low blood sugars until they are too confused to help themselves. Helping patients overcome this problem is difficult. Recently, subjects with type 1 diabetes and hypoglycemia unawareness were found to display brain activation patterns during hypoglycemia that resemble the activation patterns seen following the administration of an addictive substance such as cocaine; raising the possibility that hypoglycemia may be perceived as rewarding and not a stress to patients with hypoglycemia unawareness. If so, therapies applied to the treatment of addictions like naltrexone might provide a novel treatment approach.
In this project we will test the hypothesis that naltrexone therapy in subjects with type 1 diabetes and hypoglycemia unawareness will reduce the number of reduce the number of hypoglycemic events, improve recognition of hypoglycemia, and normalize the brain activation patterns seen during hypoglycemia. Our specific aim is to perform a randomized double blind trial of four weeks of naltrexone or placebo therapy in twenty subjects with type 1 diabetes and hypoglycemia unawareness and compare the outcome measures collected before treatment with those collected at the end of the treatment period. This work is significant because it will investigate a novel treatment approach to the serious problem of hypoglycemia unawareness in type 1 diabetes.
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 area of hypoglycemia, which is the factor that limits the intensity with which glycemic control can be applied to reduce the microvascular complications of diabetes. Neuroimaging data now suggest that recurrent hypoglycemia may alter brain function so that hypoglycemia is no longer perceived as a threat and may be experienced as rewarding. A similar change in function is seen in patients with substance abuse upon exposure to addicting drugs. These patients have been successfully treated with naltrexone and the purpose of this study is to determine if naltrexone can help with the treatment of hypoglycemia unawareness.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
If this study shows that naltrexone is effective in treating hypoglycemia unawareness, it could ultimately be used to restore the sensation of the warning signs of hypoglycemia in patients with hypoglycemia unawareness. If such patients were able to sense their hypoglycemia, they could more safely manage their blood sugars and reduce their risk for developing the complications of diabetes.
Why is it important for you, personally, to become involved in diabetes research?
Diabetes is a devastating disease requires attention on a daily basis and holds out the possibility of developing serious complications over time. I became involved in diabetes research to develop new ways to prevent diabetes complications and to improve the lives of people with diabetes. As a clinician, it is very important to me that until there is a cure, my patients live long and well with their diabetes. All of my research to date has been focused on achieving this goal.
What role will this award play in your research efforts?
This award will significantly advance my research efforts because it will let me determine if a readily available drug can be successfully used to treat hypoglycemia unawareness, a condition that can seriously impact quality of life and complication risk. This award will also allow me to continue to mentor the next generation of diabetes researchers.
In what direction do you see the future of diabetes research going?
In the future, I believe more effort will be spent to understand the changes in integrative physiology that are responsible for the development of diabetes and its complications. With this understanding, new therapies can be developed. The impact of diabetes on cerebral function will also receive more attention since so many patients are now living healthy lives with diabetes into old age. Finally, I believe future research will also provide better strategies to achieve diabetes prevention.
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