Doctors In-Depth: Breath Test For Diabetes

Here's the 6 On Health report from Thursday, March 6, 2008. KFDM.com wants to continue to bring you the most complete health news online.



The following is Q&A with Pietro Galassetti, M.D., Ph.D., about a new breath test for diabetes patients to check their blood sugar levels.



What happens in the body during a hypoglycemic attack?...

Dr. Galassetti:  Your blood sugar is very jealously controlled. Your body knows the blood sugar must be really tightly controlled. When you have changes in sugar, both high and low -- when it's low we call it hypoglycemia, and if you go about half your normal level, that may be enough to make you feel very, very uncomfortable -- sweaty and dizzy. If you go a little below, you eventually lose consciousness, get an epileptic crisis or even worse. That is for the low part. For the high part, if you go above 100, which is your average, if you go about 200/300, you are not going to feel anything immediately, but that level is enough to do a little bit of damage in your arteries. That damage, if it last for years and years like in a diabetic, would build up enough to give you cardiovascular problems throughout your body. If you go much higher than that, like several 100's, like 500/600, then you may have actually ketoacidosis and you can even go into a coma from too much sugar. That is normally very unusual, even in the diabetic, but it is also how diabetes is diagnosed -- when it's initially uncontrolled because somebody doesn't know and they get a very extreme level of blood sugar and go into a coma -- then they are diagnosed. In the normal life of a diabetic, comas are very unusual because even with bad control, they never go down.

So the key for them is to always keep it at this level?

Dr. Galassetti:  Exactly. In a non-diabetic person, the body does it for you and you will be amazed how tight it is. When you eat a meal, your glucose will go from 100, which is your regular concentration, to about 150/160. Then your body makes insulin, brings it back down and within a couple of hours it's back to normal. The changes are very small -- within 40 to 50 percent. In the diabetic, this doesn't exist so they will eat the same meal and they may go up to 300/400 which, of course, is very dangerous in the long run.

Can you explain what methylnitrate is?

Dr. Galassetti: Methylnitrate is a compound -- it's a gas that exists in the atmosphere in small concentrations. It's one of the many gases that exist in the atmosphere. Normally, it is formed in the atmosphere through the reaction with nitrate oxide and some oxidated radicals. These are difficult words and I do not understand them that much myself -- I'm not a chemist. But probably most people have heard about free radicals, these bad things that hurt your body and are counteracted against by antioxidants. What happens when there is some of this oxidation, same as what happens to free radicals, some of these gases like methylnitrate form inside your body. When you have high blood sugar, some of this oxidation increases in the wrong way. That is one of the main ways high blood sugar, hyperglycemia, slowly hurts your body in the long run. This little increase in oxidation, free radicals, results in formation of methylnitrate, this gas inside your blood stream. So we have a slight increase in the methylnitrate and when the blood flows through your lungs, a little bit of this methylnitrate goes out with your breath and we can pick it up with our technique.

Tell me a little about how you are able to pick methylnitrate up in the breath.

Dr. Galassetti: Once again, it's not me -- I am a clinical investigator who is studying diabetes, but we had the good fortune here to be able to collaborate with one of the best chemical laboratories in the world - the atmospheric gas laboratory directed by Dr. Sherwood Rowland and Don Blake here at UCI. They set up this incredible machinery to pick up concentrations of gases as low as ten parts per quadril units, it's a concentration so small it's hard to imagine. This means is that in a single breath, they can measure hundreds of different gases. When I went to med school they taught me that there is about ten gases in the breath. They tell me there is 1000 because it depends on how low you can go in the concentration. So they can measure those gases and we can create the metabolic condition so those gases become meaningful.  The collaboration between the two groups has gilded these very interesting observations.

When a diabetic goes into one of these attacks, methylnitrate goes up?

Dr. Galassetti: Yes. The study was done in children born with diabetes. The children come to the laboratory in the morning. We didn't tell them to control their blood sugars. We told them as they always do to try to keep the glucose as best they can, but what it means is it will be all over the place.  Some children came in with normal blood sugar, 100. Some children came in with values of 400, which is extremely high.  We had them come in and there were several hours, of course, the children that had high blood sugar, we gave them insulin and corrected the blood sugar -- gradually bringing it back down to 100. We kept the children who had normal blood sugar at a normal level. What happened is we also simultaneously collected the breath gases in a container like this. This is a specially built canister that is vacuumed inside and electric polished. You simply breathe into this tube and it will collect your breath. That is how we do our gas analysis down in the laboratory. We collected these gas samples and then we measured simultaneously the sugar in their blood and the gas content. We saw that the children who had high blood sugar had a very high level of methylnitrate in their breath. As we gradually corrected the blood sugar, the methylnitrate in their breath came down. The children who had normal blood sugar, had low methylnitrate, remained constant for the three or four hours of the experiment. So that meant that the two factors were correlated. That doesn't mean that we can use one to predict the other, but we can definitely use one as part of the final equation to estimate one from the other.

What might this breath test mean for a diabetic down the road?

Dr. Galassetti: Two things -- one thing could mean in terms of the affect of high blood sugar in their health, methylnitrate may be one of the mechanisms by which high blood sugar actually determines its deleterious affect, which we know some of the mechanisms are still not completely clear. So methylnitrate is probably one of the metabolites that hurts your arteries in the long run and eventually results in the cardiovascular complication of diabetes. From our point of view, on the bright side, this might be a very useful tool for us to follow and although it may not be the only method we would use -- we would most likely use an equation incorporating several gas profiles. But methylnitrate would definitely be one of the gases we will incorporate in our predicted models. The idea is they will let us calculate glucose in the blood without having to draw the blood -- just estimating from the breath.

Is this something a patient might be able to have themselves and use at home?

Dr. Galassetti:  That's our hope. It's very hard to predict when this will happen but the whole point of the sub studies is not just for academic interest -- that would be selfish of us. The whole point is to improve the technique to the point that this measurement would be performed in much smaller, less expensive and less complicated devices. Ideally, the devices would be available to the patients at the pharmacy or doctor's office or their own home, just like they have hand held units now to check their blood sugar. Hopefully, instead of pricking their own blood, they will be able to blow into this device and measure their glucose concentrations and ideally, not only their glucose concentrations -- unlike other techniques that are being developed right now that only focus on blood sugar. The flexibility of our technique, because we measure so many hundreds of possible gases, is that we may be able to track other variables that are very relevant to diabetic patients and to patients subject to a lot of different conditions. This includes possibly insulin -- there are very promising preliminary results that allow us to calculate insulin as well in the breath -- possibly lipids, cholesterol and other variables. This is all very preliminary but down the road, and I hope this will be five to ten years but this is a guess at this point, we will be able to provide hand held devices available to everybody.

So it might even help people with other diseases?

Dr. Galassetti: Absolutely. Because of the series of studies we have started -- methylnitrate which is diabetes, that is what we focus on. But we have simultaneously different studies on this technique and one of them is actually the detection of pulmonary infections in patients with cystic fibrosis, for example. We already published a paper a couple years back in that field. We are trying to develop for example, signatures of gases produced by cells in culture -- white blood cells, your immune cells, in culture actually produce gases and we are looking at that. We are trying to find out whether the cells undergo some alterations, or have gas profiles we may pick to identify for particular conditions. Potentially, the range of applications is very broad and hopefully we will be able to apply this to many diseases -- hopefully tumors for example. That is another possibility -- but once again very preliminary, but it's very possible -- and a number of other diseases as well.

Overall, what would you say is the most significant part of your study?

Dr. Galassetti: Ideally, the whole purpose of our series of experiments is to transform this technique, which is now very expensive and complicated, into something that will be eventually done with a lightweight and inexpensive device available to patients both with diabetes and possibly with other conditions. But being able to predict exactly how long it will take to go from our status to the actual development of this device is very difficult at this point. I hope it will be within five to ten years, but this is, of course, a guess at this stage and we don't know how that might work.

Aside from just the pain of having to prick your finger all the time, what are the other benefits for a diabetic taking a breath test as opposed to actual blood?

Dr. Galassetti:  The prick is not very painful, but doing it five times a day all your life becomes very obnoxious -- what happens is the area of skin around your forefingers actually hardens. So it's not a matter of preventing a little amount of pain, which is preventable, but with the long term changes in your skin which is very unpleasant. Even if that were not the case, one of the main advantages may be for people who do not have diabetes but are tested for screening purposes, and who refuse to be screened because of the invasiveness of blood draws. It's true for glucose, for insulin testing, for pre-diabetes, the diagnosis and so on. For the broad spectrum, screening tests, screening programs -- school based, community based -- this is an ideal technique because we will need to diagnose the condition. Then it won't hurt for people who test themselves even four, five, ten time a day. The easier the technique, the more likely is that they will do it. It is controlled and you improve dramatically. Ideally, you would want to know where the blood sugar is at any moment of your life. That is impossible to do in realistic terms but the more you do it, the easier it would be to achieve ultimate control. There have been major studies conducted on positive patients and the two things that are very related -- the better your glucose control throughout the day, the less your chances are of cardiovascular complications in the long run. That is one essential thing -- keep your glucose as close as possible to normal values and you will prevent all your bad complications. Diabetes is not going to kill you today or tomorrow -- that is why it's a silent killer -- it will hurt you very slowly and then catch up with you 30 or 40 years down the road with a stroke or a heart attack or renal insufficiency and so on. All this can be prevented but it's really related to how well you can control your glucose on a daily basis. So that is how you can improve your control and make it easier and more accessible.

Pietro Galassetti, MD

University of California, Irvine

Orange, CA

pgalasse@uci.edu