Closer to a Cure

Link to Harvard Science article re: diabetes cure trial
Full article below:

Initial human trial of Type 1 diabetes treatment begun

Tuberculosis vaccine proved promising in mice

March 13, 2008

Emily Parker
Massachusetts General Hospital

Scientists at the Massachusetts General Hospital (MGH) have initiated a phase 1 clinical trial to reverse type 1 diabetes. The trial is exploring whether the promising results from the laboratory of Denise Faustman, Associate Professor of Medicine at Harvard Medical School, can be applied in human diabetes.

A phase 1 trial is usually designed to determine the safety, side effects, and dosage range of a treatment, rather than its usefulness. If the proposed treatment is found to be safe, then researchers may initiate a phase II trial, to test for efficacy, in a relatively small group of subjects.

In previous studies Faustman has demonstrated that mice can be cured of a form of diabetes closely resembling type 1 in humans. Those studies used Bacillus Calmette-Guerin (BCG), a common tuberculosis vaccine, to deplete the abnormal immune cells that attack and destroy the insulin producing cells of the pancreas. The first step in the human study, which is currently enrolling volunteers, is to determine whether the same strategy using BCG vaccination can be used to modify the abnormal autoimmune cells present in type 1, or so-called "juvenile onset" diabetes.

David M. Nathan, MD, director of the MGH Diabetes Center, who is leading the human study at MGH, cautions that this “this is the very first step in what is likely to be a long process in achieving a cure. We first need to determine whether the abnormal autoimmune cells that underlie type 1 diabetes can be knocked out with BCG vaccination, as occurred in the mouse studies.”

“We are pleased to be starting human clinical trials,” Faustman said. “Human trials take time, but we are making the step from curing diabetes in mice to determining whether it will work in men and women with diabetes.”

Type 1 diabetes, which usually begins during childhood or adolescence, is triggered when the immune system attacks and destroys the insulin-producing cells in the pancreas. In the absence of insulin, which is necessary for sugar and other nutrients to enter cells, blood sugar levels rise and can cause a variety of severe complications, including kidney failure, loss of vision, amputations, heart disease, and strokes.

The risk for developing complications is closely linked to the elevated blood sugar levels over time. If blood sugar levels are well controlled, the onset of long-term complications can be delayed, and sometimes largely avoided. However, the intensive, on-going therapy required to maintain near-normal sugar levels places life-long demands on the patient, including frequent blood sugar monitoring and at least 3 daily injections of insulin or use of an insulin pump, along with restrictive diets. Insulin doses must be adjusted based on blood sugar levels, dietary factors, and anticipated exercise. Thus, a cure for diabetes has been highly sought after and has attracted much research interest.

The clinical trial is using the BCG vaccine because it causes a low-grade inflammatory reaction, which in the mouse model of autoimmune diabetes lead to the destruction of the abnormal autoimmune cells. It is a particularly attractive candidate vaccine because it has been used safely for nearly 80 years as a tuberculosis vaccine.

The Phase I trial is being supported largely through direct and fund raising support from the Iacocca Foundation, and through support from other donors and the Massachusetts General Hospital. The Iacocca Foundation was founded by Lee Iacocca and his family in 1984 to fund innovative approaches to a potential cure for diabetes.

Prospective trial participants should contact the MGH Diabetes Center at 617-726-1847.

Very High A1c

Allie had a quarterly checkup yesterday. Her A1c (a test which measures the average blood glucose level over a 3-month period) had gone up astronomically. It was 9.7! If you have a child with type 1 diabetes, you cringed when you read that number, which is what I did in the doctor's office.

I knew that Allie hadn't been keeping a close check on her sugar, and that she has an unhealthy habit of skipping lunch at school, then "grazing" the rest of the day, evening, and night. The doc said something has to change (obviously), because Allie's no longer in the "safe" zone and skyrocketed right through the "unsafe" zone and nearly touched the "danger" zone with her A1c number.

What that means, basically, is that her blood sugar has been consistently high enough to start damaging her kidneys, eyes, and heart and that she's more in danger of going into ketoacidosis which can be fatal. I think she was upset enough in the doctor's office that she will take this seriously and start doing what she needs to be doing to stay healthy.

This disease sucks. I hate that Allie has to go through this; that anyone has to go through this. It's heartbreaking. It's a loss of freedom. WHERE IS THAT CURE?

Symptoms and Diagnosis of Type 1 Diabetes

I've started this blog not only because my daughter has Type 1 Diabetes, but so that hopefully some of this information will be helpful to someone. If you have surfed into this blog because you searched for symptoms you or your child may be having, read on.

Some of the symptoms of type 1 diabetes:

excessive hunger
excessive thirst
frequent urination
sweet or fruity smelling breath
weight loss
vomiting
nausea
abdominal pain
fatigue

Before my daughter, Allie, was diagnosed on October 18, 2006, she had been having some of those symptoms, but not all. She was 12 and sooooo incredibly active with skating (skateboarding), running around, jumping on her pogo stick, etc., that I think she burned up a lot of the sugar that had been accumulating in her blood and her symptoms weren't too dramatic.

It all started with having to pee constantly. We couldn't get through a soccer match without her needing to go. Then on the drive home from the game, she'd have to go. Then once again when we got home. I didn't think too much of it initially. We had just moved back to Arizona from Virginia and it was HOT and so she was drinking a lot of water....

Allie had also lost nine pounds, but I didn't know that until she was weighed in at the doctor's.

She was also eating us out of house and home. She'd eat dinner, then have seconds, then come back to the table once everyone else was finished eating, and finish what was left. Then she'd complain later I never made enough food for dinner. I attributed it to puberty. She had always been a big eater, anyway.

Oddly, the thing that finally made me think something not good was going on was that Allie started having leg cramps in the middle of the night. They would wake her and she'd be lying there screaming. Two nights of that had me calling the doctor--finally. The peeing and hunger had been going on for probably about a month, but in every other way, she was fine. No fever, no loss of energy (I remember her coming in every day to tell me how many continuous jumps she had made on her pogo stick...over 1,000 at a time), so it never occurred to me that something was really, really wrong.

What was wrong was that her body's immune system was destroying the beta cells in her pancreas and her body was slowly losing it's ability to produce insulin and use glucose. Allie was slowly starving to death and I didn't even realize it.

Fortunately, our doctor suspected type 1 diabetes right away and had Allie give a urine sample. It was positive for sugar and ketones (key-tones). In a daze, I asked what that meant, although in my heart I knew Allie had diabetes--even though I didn't quite know what that meant in itself. That was when the doctor told me that sugar shouldn't be there at all, and ketones meant that she was burning fat instead of glucose for fuel and that her body was starving.
We went to the lab for more specific tests and they all came back positive for type 1 diabetes. Allie was admitted into Phoenix Children's Hospital (PCH) and we stayed for three days to learn how to physically survive this disease. I was completely unprepared for the emotional side of it all.

I remember Allie's face when the doctor called with the lab results. I was on the phone with the doc and Allie was standing across the kitchen island watching me. I'm sure my face gave her the answer. I looked at her and just nodded. Her eyes got wide and she smiled--not a happy smile, of course, but one of disbelief.

After hanging up the phone, I told Allie that we had to go pack and that we'd be in the hospital for a few days. I really didn't have any more information than that. She went to her room to pack and I called my husband, Todd, and asked him to come drive us. I was shaking so badly I knew I wouldn't be able to drive us to PCH. My world was disintegrating and I couldn't hold it together.

As Todd & I packed in our room, Allie knocked on our door. I opened it to find her there crying. I hugged her and asked what was wrong (other than the obvious). She asked if she would ever be able to eat cupcakes again (she's an fantastic baker). I half laughed, half cried, and told her that YES! she would be able to eat cupcakes again. I don't know how I knew that, but I felt it was true.

At the hospital later that day, we found out with certainty that Allie could indeed eat cupcakes again. We learned that she would be able to eat whatever she wanted, whenever she wanted, but that she had to count all the carbs in the food (and subtract the fiber since it doesn't affect blood sugar, even though it's a carbohydrate), and then use her insulin-to-carb ratio to calculate how much insulin it should take for her body to use the food she was to consume.

We also learned about correction factors for the inevitable times that her blood sugar would be too high and she would need to bring it back down to a safe level. We learned how to bring it back up with a "quick sugar," like glucose tablets or juice or non-diet soda when it dropped too low. We learned to use syringes and draw up the insulin properly. We learned about the different types of insulin and what they're for.

Allie uses Lantus to handle the small amounts of sugar released by the liver into the bloodstream 24/7. One shot of Lantus lasts about 24 hours. She uses NovoLog, a fast-acting insulin, for meals, snacks, and corrections. NovoLog lasts about 3 hours. We learned an amazing amount of information during our stay at PCH. Then it was time to go home.

I cried a lot at the hospital (Allie was fine with it all and so brave) and cried when it was time to go home. If you have children, you may have felt a small bit of panic at the thought of taking that little baby home and knowing she would be dependent on you to keep her safe. I felt that way taking Allie home with type 1 diabetes. I was scared to death.

I think we experienced her first low the evening after we arrived home. I can't remember the number, but it was pretty low, in the 60's I think. We treated it, it came up, she was fine. I hid in my closet and cried. I cried for our old life. I grieved for Allie's loss of freedom to just grab a snack and eat it without having to count the carbs, draw up insulin, give an injection then wonder if it would be the correct amount. My heart sank every time she left the house. I worried she would go low and pass out in a ditch somewhere, or that she'd go too high and die from ketoacidosis. I just wanted to keep her home all day, every day and stare at her. Of course I couldn't do that. Allie would never have allowed it.

As of this post, it's been a year and a half since Allie's diagnosis. She has handled it well all along and has maintained decent A1C's (a measure of blood sugar over a 3 month period). Having type 1 diabetes doesn't keep her from doing anything she wants to do. Sometimes I keep her from doing things she wants to do, because I'm not as comfortable with it as she is. For the most part, though, I don't hold her back. She's had some scary situations, like going so low at the mall with her friend that it wouldn't even register on her meter. That was almost a 911 situation. Then she had another one of those at the movies; we were all there together and she chugged her brother's root beer and her Icee. Allie's also had days on end that she couldn't get her blood sugar below 250 no matter how much insulin she injected. There have been those 600 days, too. Not fun.

Allie tried the insulin pump for a while, but found it too uncomfortable. I'm glad she tried it though; it changed her. I guess she had lost a little of her infectious zeal for a while after the diagnosis. The pump gave her her freedom to snack back. The Cozmo pump has a little bolus button on the side that we affectionally called "the snack button." We programmed the button to deliver enough insuilin to cover 5 grams of carbs per push. That made snacking sooooo easy! Having that freedom back brought that little spark back to Allie that had been missing. So, even though the pump sits unused on our pantry shelf now, that's okay. It served a great purpose even though in the long run it wasn't for her. Maybe someday she'll change her mind and use it again.