Diabetes Forecast May 2004

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FOR TYPE 1

Research Profile

Hypoglycemia Unawareness
Can Beta Blockers Help?
by Terri Kordella

"Hypoglycemia unawareness is a vicious cycle," says Christian Meyer, MD.	Christian Meyer, MD Occupation Director, Clinical Research Center, Carl T. Hayden VA Medical Center, Phoenix Associate Professor of Clinical Medicine University of Arizona Professional Focus Glucose metabolism, hypoglycemia Outside Interests Travel, tennis, skiing Research Funding ADA Career Development Award

Have you ever experienced low blood glucose that seemed to strike out of the blue? No shakiness, no dizziness, no heart palpitations, no sweating or hunger, just wham, one minute you're feeling fine and the next you can't think straight, you're wobbly on your feet, and you're slurring your speech?

That's a condition called "hypoglycemia unawareness," and it's a complication of diabetes, usually of type 1. The more frequent or severe your episodes of low blood glucose (hypoglycemia), the more likely you are to develop hypoglycemia unawareness.

The symptoms of hypoglycemia occur when your body releases hormones called catecholamines. However, if you have diabetes, and you experience frequent episodes of hypoglycemia, something can go awry with this natural warning system.

"It may be that the body loses sensitivity to catecholamines," says Christian Meyer, MD, director of the Clinical Research Center at the Carl T. Hayden VA Medical Center and associate professor of Clinical Medicine at the University of Arizona and recipient of an American Diabetes Association career development award. Meyer is using his Association funding to explore a potential treatment for hypoglycemia unawareness that would help the body become more sensitive to catecholamines.

Old Drug, New Use?

Meyer's study involves propranolol (Inderal), a blood pressure medication in a class of drugs called beta blockers. Meyer chose this drug to study because beta blockers have been shown to increase sensitivity to catecholamines in people who have congestive heart failure.

Thirty people with type 1 diabetes and hypoglycemia unawareness will participate in the study. First, the researchers will measure exactly how severe hypoglycemia awareness is in all participants. To this end, participants will come to the research center for an over-night stay, when their blood glucose will be stabilized. The next day they will receive an IV infusion of insulin and varying rates of glucose to lower their blood glucose in steps, each step lasting 45 minutes, until finally the participants' blood glucose is 42 mg/dl. During the study, the participants will complete questionnaires about their symptoms to determine the exact blood glucose level at which they recognize hypoglycemia.

If you've ever had a low of 42 mg/dl, this might seem frightening, particularly if you're used to having symptoms. But Meyer anticipates that most participants won't feel many symptoms because of their hypoglycemia unawareness.

Next, 15 of the participants will be assigned to take the beta blocker for four months. The other 15 participants will take a placebo (dummy pill). Neither the participants nor the researchers will know who is taking which pill.

After four months, the participants will stop taking pills for four days. Then they will return to the research center to retake the incremental blood glucose-lowering test. The participants will again fill out questionnaires as their blood glucose is lowered to determine the level at which they recognize hypoglycemia.

"Once all participants have completed the entire study, we'll find out who took the beta blocker and who took placebo, and see whether the people who took the beta blocker experienced symptoms of hypoglycemia earlier," Meyer explains.

If so, that would indicate that the beta blocker increased sensitivity to hypoglycemia.

"Hypoglycemia unawareness is a vicious cycle. The more you experience hypoglycemia, the more likely you are to develop hypoglycemia unawareness, which in turn leads to more frequent hypoglycemia," says Meyer. "But it can be reversible. If you experience warning symptoms early enough during the development of hypoglycemia, you can treat it before it becomes more severe. The fewer episodes of hypoglycemia you have and the less severe they are, the earlier you'll recognize them. My idea is to improve the recognition of hypoglycemia by restoring the sensitivity to catecholamines using a beta blocker, and break the cycle."