Oct 17, 2014 — Life with diabetes is hard enough but those who take medicine to control their symptoms can experience hypoglycemia, or low blood sugar, that if left untreated can lead to, seizures, coma or even death. While most diabetics experience warning symptoms, such as shakiness or hunger, 20% of type 1 diabetics do not, meaning they don’t know that they need to take action to raise their blood sugar to safe levels. Dr. Simon Fisher, co-director of the Diabetes and Metabolism Center at the University of Utah, describes hypoglycemia unawareness and his search for drugs to alleviate the problem. He also explains why support from nonprofit organizations such as JDRF, which supports his work, has become increasingly important in recent years.

Interview

Interviewer: Many diabetics experience dangerous fluctuations in blood sugar levels but the problem is compounded and what they don't even know it's happening. Dr. Simon Fisher explains his research to combat hypoglycemia unawareness work supported by the JDRF.

Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.

Interviewer: I'm talking with Dr. Simon Fisher Co-Director of the Diabetes and Metabolism Center at The University of Utah. Dr. Fisher before we get into the research I wanted to talk about the role of non-profit organizations. Your work is funded by the JDRF and I think we're becoming more familiar with other visible campaigns such as the ALS Ice Bucket Challenge. It seems that these organizations are becoming more prominent these days.

Dr. Fisher: As you know the National Institute of Health, our Federal Government, is under a lot of financial restraint and they're very selective of giving out money, and money's tight all around, so the actual rates of funding from the National Institute of Health has not grown in the pace that research is. So there's an incredibly important role and we rely on agencies to fund our research. So the JDRF focuses on Type I Diabetes based research. Everyone has their own interest, personal connections to family members who may have this disease, and I guess we're talking about diabetes, and it's very important for them to feel that they're doing something that is leading towards you know better treatments or a cure, and every agency has their own agenda so to speak that allows them to put money where they think it needs to go.

Interviewer: Your most recent grant from JDRF is supporting your research investigating complications associated with diabetes. So it stems from this paradoxical observation that diabetes causes high blood sugar levels but one of the major problems of diabetes is hypoglycemia, or low blood sugar, how does that happen?

Dr. Fisher: Because we're treating diabetes better and better and getting more and more aggressive and trying to get blood sugar down to normal or even below normal levels the incidence of hypoglycemia, that's low blood sugar, has now eclipsed that of high blood sugars in terms of hospital admissions. People are coming in now because we're treating them more and more aggressively. These low blood sugar reactions can be mild, I mean they happen every day, or every other day for people who have tightly controlled blood sugars.
The problem is as it happens more and more they run the risk of having neurological problems. Again, what happens is your ability to defend against this low blood sugar becomes impaired over time your brain runs almost exclusively on blood sugar so as your blood sugar drops your brain starts having problems functioning, sadly. You get, it can be as mild as a confused, a little disoriented, but it can cause people to pass out if your blood sugar gets low enough. It can cause people to have seizures if your blood sugars get low enough and a recent study we published shows that low blood sugar actually is fatal. If your blood sugar is low enough for long enough people die.

Interviewer: Wow. Now normally people know when they're becoming hypoglycemic, right? There are different warning signs that the body give you?

Dr. Fisher: Right so you can imagine as your blood sugar gets low and your brain stops functioning it's a flight or fight stress response. Your brain activates your adrenaline, your epinephrine, your norepinephrine, other hormones in your body help bring your blood sugar back up. What I'm studying in our laboratory is hypoglycemia unawareness. What happens is your body doesn't get these traditional warning signs, you don't get hungry. For example, you don't go, "Gee my blood sugar is low," and go get something to eat, go grab a glass of orange juice, etcetera
Nocturnal, that is night time; low blood sugar is particularly dangerous. People with diabetes and hypoglycemia unawareness don't wake up in the middle of the night. This leads to the unfortunate "dead in bed" syndrome, which is as horrible as it sounds.

Interviewer: Well obviously it's a very serious problem and your approach is to study it in an animal model.

Dr. Fisher: Right, that's the novel part about our research, is we've now created an animal model to investigate hypoglycemia unawareness. So the trick for many, many years is how do you get an animal model to respond hypoglycemia unawareness? In humans it's easy you say, "Do you recognize that your blood sugar is low?" And we lower their blood sugar and they say, "Yeah I feel horrible," and I go, "Okay you're aware of hypoglycemia."
For people with long standing diabetes if we lower their blood sugar into a low level and they say, "No I don't feel anything at all." They're by definition hypoglycemia unaware. You can't ask a rat...

Interviewer: No I guess not.

Dr. Fisher: ...if they're, how they're feeling. So what we've done is we've modeled this by saying, "What is going to help somebody if their blood sugar is low?" Basically they need to go and get food. So what we're doing is we're measuring how much food our rat takes when his blood sugar is low, and in our model now what we've done is we make the rats who are currently hypoglycemic, similar to patients that take insulin every day, and if their blood sugar gets you know low one day or the next day they're at high risk for hypoglycemia unawareness the next day and that's what happens in our rats.

Interviewer: So the rats who get food are aware, at least subconsciously aware of their hypoglycemic condition. The rats that don't eat are hypoglycemic unaware.

Dr. Fisher: Right, and so what the JDRF has, the goal of their research is to say, "Well what we can do to make people more aware?" So essentially what we're doing is a drug screen. We're giving many different kinds of drugs that act in the central nervous system to these rats, these rats that we've made hypoglycemia unaware, and then we're seeing which drug is really going to make them say, "Oh geez I feel horrible I've got to go eat," and any drug that can help them decide to go eat is a drug which is enhancing hypoglycemia awareness.

Interviewer: Now I noticed in your drug screen that you're screening through drugs that are already FDA approved for other conditions. Is there reason that you're taking that route instead of screening through new compounds for example?

Dr. Fisher: There are several reasons. One is, technically it's easier. These drugs are all FDA approved so we can just pull them off the shelf and you know throw them into rats and see if they work. Secondly, from a practical point of view if we want to get something to a patient as quick as possible if we find drugs that really show clear promise in rats we can jump immediately to clinical trials because these drugs are already FDA approved, we can accelerate the pace of research and get it into people sooner rather than later.

Interviewer: And what do you think is a realistic time frame of going through the screen and getting a drug to clinical trials.

Dr. Fisher: So obviously these studies need to be done in rats first then we'd probably do it in a large animal model then we could relatively quickly move into a human model. So that's why, again I'm trying to take my clinical experience and seeing people suffer out there with severe low blood sugars that were admitted to the hospital, they were driving their car, they passed out because their blood sugar was so low they crashed, they took away their license, and as a Diabetologist I want to get them back and functional and living a normal life. What I'm hoping is that my study will have a translational aspect so I can get drugs into humans that might benefit them so that they can live full, meaningful, and productive lives.

Announcer: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences Radio.


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