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Dr. Nancy Bohannon is actively involved in diabetes research and operates a full-time private practice in Internal Medicine, specializing in Diabetes and Endocrinology. Recently Dr. Bohannon spoke to Scott King via telephone from her office in San Francisco about current protocols available for predicting and preventing Type 1 diabetes.
Scott King: Is there anything new on the diabetes prevention front? Is there anything exciting?
Dr. Bohannon: Yes, very exciting. We now are very able to predict Type I diabetes through islet cell antibodies, the GAD antibody and insulin antibodies. When we use these three tests for antibodies together, we really can get quite good at predicting Type I diabetes, but these are expensive research tests that are not appropriate to use on the entire population. However, first degree relatives of Type I diabetics-meaning mother, father, brother, sister, or child-are appropriate subjects for these protocols.
These protocols are being done by several people: Stuart Soeldner at UC Davis, George Eisenbarth, who has left Joslin and is now at the University of Colorado in Denver, and Noel Maclaren, who is at the University of Miami. They're all involved in these prediction studies, so if patients or their physicians make contact with these researchers, they can have the blood of their first degree relatives studied. The tests should then be repeated every year or two, depending on the age of the person, to see if these antibodies are developing.
Now, once the person has developed the antibodies, the study that needs to be done is not an oral glucose tolerance test but an intravenous glucose tolerance test which can be done in the doctor's office, if the doctor is used to doing them.
Scott King: So instead of drinking the glucose solution...
Dr. Bohannon: It's given intravenously, and then the blood is drawn at one minute, three minutes, and several times after the intravenous bolus and sent to have measurements of insulin taken. That reflects how quickly the pancreas is able to put out insulin. By measuring insulin and determining what's called the "k" value (which reflects the amount of insulin and how quickly it's coming out of the pancreas), they can determine whether this person is likely to develop Type I diabetes within the next six months to a year.
Now if it turns out that it looks like the person has in fact lost half or more of their Beta cell secretary capacity and they are really destined to become diabetic in the near future, then they can be entered into a protocol to try to prevent the development of diabetes. These are the exciting protocols.
Most people who get tested for these antibodies are going to be negative-less than 2% are going to be positive (that is, have significant amounts of antibodies). And of those, some people are positive for years and years and never develop diabetes. So the IV glucose tolerance test has to be done to see which of them would be likely to develop diabetes in the near future. We're talking about screening thousands of people to just get a handful of people who would be appropriate for the prevention protocols.
Prevention protocols have varied over the years. They started out with cyclosporin, immuran, plasmapheresis, prednisone, and other drugs that were really fairly toxic.
Scott King: These were to blunt the immune response that was destroying the islet cells?
Dr. Bohannon: Yes, either to blunt the immune response or in some other way remove the antibodies. But a lot of the people who are going to develop Type I diabetes are obviously going to be under the age of twenty, and many of them under the age of ten. You don't want to be giving these kids very toxic substances-and they didn't really work that well either.
The prevention protocols now are primarily involved with giving either oral nicotinamide (which has not been very successful) or prophylactic (preventative) insulin-actually giving these people insulin shots to rest their pancreas and try to protect it from the onslaught of antibodies.
So these people, generally children, are being given shots of insulin one or more times a day, depending upon which protocol they're in. They may actually have to go into the hospital for five to seven days on the Bio-Stator (the big "artificial pancreas") with IVs running in both arms to totally put their pancreas at rest. They can then be sent home on their usual diet and exercise program (not a special "diabetic" one) and are given insulin one to four times a day.
Scott King: Does that stop the immune response?
Dr. Bohannon: Taking insulin so far has been very promising. I don't think anybody who was predicted to develop diabetes within the next six months (who was caught early enough and started on the protocol) has yet developed diabetes.
Scott King: Do they keep taking insulin?
Dr. Bohannon: They keep taking insulin indefinitely. In one of the prevention protocols, they go back into the hospital every nine months to a year to be put on the artificial pancreas for five to seven days and then they are sent home again with insulin.
Some people may say, "If I have to take insulin, then that's as bad as being a diabetic." It sure is not, because they don't have to follow a specific diet plan or eat at certain times, and they don't have to follow an organized exercise program. They don't have to do anything except take the shots. They don't have to prick their finger and check their blood sugar. As far as I'm concerned, the shots are the least of any kind of a diabetic program-far harder is following the diet, the exercise programs, and doing the blood sugars. And so they're given small amounts of insulin, not enough to get hypoglycemic, but enough to supply at least about half of what the pancreas would normally be making. That way the pancreas doesn't have to work as hard.
Scott King: Why wouldn't the body continue to destroy the pancreas even though the patient is taking the insulin?
Dr. Bohannon: A lot of it is that the pancreas is not having to work as hard. Any organ that is working hard is going to be destroyed more rapidly by auto immune processes that are going on.
Scott King: Is taking insulin the only therapy available for preventing diabetes?
Dr. Bohannon: There are other prevention protocols in the world, such as using nicotinamide or azothiaprin, but the active ones in this country that are still accepting subjects are really centered on insulin. Dr. Maclaren in Miami is giving insulin by mouth for those patients who have islet cell, GAD, and insulin antibodies, but who have a normal IV glucose tolerance test.
His protocol is to give insulin by mouth, which sounds very strange because we all know that insulin is broken down in the gut and digested. It appears, based on some of the research he's done on rats, that exposure to insulin, even orally (and rats might be very different from humans), can somehow tie up or stop the antibody production.
Scott King: Now that's counter-intuitive, because as you've told us before, insulin is a protein-it's like a hamburger. It just gets digested.
Dr. Bohannon: As I say, rats may be different from humans. Dr. MacLaren hasn't had anything done on humans yet, but he's going to start this protocol in people who do not look like they're going to develop diabetes in the near future and see if he can prevent it.
Scott King: Do you recommend for relatives of your Type I patients to be tested?
Dr. Bohannon: I offer it to all of the first degree relatives of all my Type I patients. I offer the screening procedure to them, realizing that this is a research protocol and it may be six months or more before we get the results. This is not like a standard laboratory test. Now, you can get these tests done commercially, but they're not as reliable.
If you really want to get involved with this, I would recommend that you volunteer for a research protocol at one of the major centers. UC Davis is doing it, University of Florida is doing it, and now that Dr. Eisenbarth is in Denver now, he's doing it there. So there are several good centers scattered around the country. Individual doctors are unlikely to want to get involved for one or two patients, but people can certainly contact Dr. Soeldner at UC Davis and find out how he can go about collecting their blood.
If someone told me, "Look, you're going to get diabetes in six months. You can either wait until you get diabetes and have to follow a diet, exercise on schedule, take your shots, and check your blood sugars, or you could start taking insulin six months earlier and try to prevent it," boy, I'd take the insulin!
0 comments - Nov 1, 1992
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