In This Chapter
5o much is being discovered every day in T1DM that I could write this whole book on that aspect rather than limiting it to a chapter of ten items. It's a very exciting time! I'll even go so far as to predict that you'll see your child cured of T1DM in your lifetime.
1 In the area of prevention and diagnosis, T1DM is being broken down into subgroups based on new findings in genetics. New substances are being found in patients' blood that suggest the diagnosis much earlier.
1 In the area of monitoring, new tests are being developed to show much earlier responses to treatment. New devices are coming on the market for testing the blood glucose continuously and painlessly.
1 In the area of complications, doctors' understanding of the mechanism of complications is expanding. They're getting down to the details of the transition from normal tissue to damaged tissue, and new substances are being found in the blood that point to the earliest development of complications.
Perhaps the most work is focused on finding a way to reverse the loss of beta cells that make insulin in T1DM. Doctors and researchers are taking all kinds of approaches, from restoring the beta cells with injections of fresh beta cells from an outside source to trying to get various cells to transform themselves into beta cells. The trouble is that these new cells are still subject to the destructive effects of the same substances in the body that destroyed the beta cells in the first place, so new drugs are being offered to overcome that difficulty. Another approach is to eliminate all the immunologic cells in the child's body by irradiation and then to restore them with new cells that may not kill the beta cells that produce insulin.
In this chapter, I provide you with ten of the latest discoveries in T1DM. Knowing that you're most interested in a cure, I discuss the most likely directions from which that cure will come. Not every approach will bear fruit, but you only need one to work in order for your child to be free of his least desired role: a person with T1DM. (See Appendix B for a list of resources that can help you keep up with the latest discoveries.)
Doctors are well on the way to major advances in type 1 diabetes prevention and treatment. It's definitely a good move for you to keep your child as well controlled as possible (or to do the same for yourself if you're the patient). After all, you want your child's body to be in perfect condition when the cure becomes available.
In 1988, two scientists at UCLA were studying genes involved in brain development and function, and they discovered the genes that caused the production of glutamic acid decarboxylase (GAD). GAD is an enzyme that leads to the production of an important neurotransmitter, a chemical that transmits information from one nerve to another. At the time, it wasn't known that GAD is also made in the beta cells of the pancreas — the same cells that produce and store insulin.
One of the original investigators then read a report about a connection between autoimmunity to an unknown protein in insulin-producing cells and diabetes. Somehow he realized that the protein was probably GAD, so he went to work to prove his hypothesis.
First he found that patients with T1DM had high levels of GAD autoantibody. Then he discovered that mice prone to develop T1DM could be protected from the disease by receiving small amounts of GAD. He and his colleagues then created a vaccine using GAD that could slow the development of T1DM even after the immune response had begun.
The next step was trying the GAD vaccine on humans, which happened in a study in which neither patient nor doctor knew whether the patient was getting GAD vaccine or a placebo. The result was that the GAD vaccine preserved insulin production without any adverse effects. The vaccine is called Diamyd and may prove to be very valuable in protecting high-risk children from developing T1DM. See Chapter 2 for more about GAD.
The Possible Prevention of Type 1 Diabetes with Oral Insulin
The Diabetes Prevention Trials in 2002 showed that oral insulin could delay or prevent the onset of T1DM. Now a much larger study is underway (it began in February 2007 and will end in seven or eight years) based on the theory that oral insulin quiets the immune system. It's set up as follows:
1 Half the patients get oral insulin in a capsule. 1 The other half get a placebo.
1 Neither the patient nor the doctor knows what's in the capsule.
The patients in this study are relatives of patients with known T1DM. Those who may develop diabetes are found to have positive tests for autoantibod-ies against insulin and another substance called glutamate decarboxylate. If autoantibodies are found, they're asked to enroll in the study.
The study will follow the patients to see if and when they develop T1DM. If nothing else, the participants will know that they may develop T1DM much earlier than they normally would know.
If oral insulin works as the researchers hope, those who get it in their capsules will get T1DM later or not at all compared to those who get the placebo capsules.
The Possible Prevention of Type 1 Diabetes with Intranasal Insulin
The basis of this treatment is the theory that exposing the mucous membranes of the nose to insulin will act like a virus to stimulate protective immune cells. These protective cells will counteract the damaging cells that destroy the beta cells that produce and store insulin (or so researchers hope).
The patients in the study will be relatives of people with T1DM who are found to have positive autoantibodies against insulin or GAD and therefore have a greater chance of developing T1DM than those who don't have the antibodies. Some patients will get insulin, and some will get a placebo, but neither the patients nor the doctors will know who got what until the study ends.
In this study, 264 people are scheduled to be enrolled by 2007, and it isn't due for completion until 2012. The patients will be studied for the development of
T1DM as well as evaluated for the development of more evidence of immunity. (This study is taking place in Australia, so it's a long way to go if you're interested.)
Another study of intranasal insulin called Pre-POINT will involve giving the insulin to children at high risk of T1DM (because they have relatives with T1DM) even before they've developed antibodies.
The Diabetes Control and Complications Trial (DCCT) published in 1993 revealed that tight control of the blood glucose could prevent complications of T1DM. Here it is about 15 years later, and most patients with T1DM still don't meet the targets of glucose control shown to be necessary by the DCCT.
The Juvenile Diabetes Research Foundation (JDRF) is funding a study of continuous glucose monitoring (CGM) to see if the technique leads to better control. The authors believe that CGM decreases anxiety about hypoglycemic attacks but may increase stress when the CGM doesn't agree with a finger stick. (The discrepancy in results occurs when there's a rapid fall or rise in the blood glucose.) The authors also are concerned that the amount of blood glucose data from CGM will overwhelm the patient and family.
CGM is also being used in a JDRF-funded study with an insulin pump wherein the pump responds to the CGM reading by supplying insulin to the patient. This is the closed-loop system that's the ultimate goal of treatment, a working "pancreas." So far the system has worked very well. It may be the temporary solution for T1DM until there's a way to replace and restore the beta cells destroyed in T1DM.
See Chapter 7 for details on home systems for continuous glucose monitoring and Chapter 11 for more about insulin pumps.
If this device pans out, you'll be looking in the mirror every time you want to know your blood glucose. Researchers at the University of Pittsburgh have developed plastic contact lenses that change color depending upon the amount of glucose in body fluids.
The glucose sensor could be embedded in regular contact lenses or worn as separate contact lenses for people without vision problems. It would change from red, indicating dangerously low blood glucose, to violet, indicating dangerously high blood glucose. A normal blood glucose level produces a green lens.
The device works by combining moisture from the tear ducts with molecules of boronic acid in the sensor to create fluorescence. A potential problem is the delay between the level of glucose in the blood and its reflection in tear ducts. This work is ongoing and may reach the market in the next few years.
Diabetic neuropathy causes pain and discomfort in the feet. Numerous drugs have been used in an attempt to reverse the neuropathy, but nothing has worked consistently until the introduction of SB-509. The drug currently called SB-509 has been found to cause the production of a protein called vascular endothelial growth factor, which helps to improve the structure and function of nerves.
In a study conducted by JDRF, SB-509 is being injected into both legs of patients who have T1DM and neuropathy three times over four months. Some people will receive the actual drug, and some will receive a placebo. The authors plan to look at pain intensity and nerve conduction velocity to look for recovery from neuropathy. They'll also look at the nerves under a microscope to see if repair of nerves damaged by T1DM is possible. The study began in 2006 and is scheduled to end in 2008.
Flip to Chapter 5 for details on diabetic neuropathy and other long-term complications that your child can avoid with tight control of T1DM.
T1DM results when the process of autoimmunity (immune damage directed back at the person rather than at an outside invader) destroys the beta cells that produce insulin. Two types of cells in the body are responsible for the immune destruction: T cells and B cells. T cells are the ones that actually attack and destroy the beta cells. B cells somehow promote the attack by the T cells.
When symptoms develop in T1DM, within three months of the diagnosis, up to 80 to 90 percent of beta cells are destroyed but 10 to 20 percent remain. The purpose of a study conducted by diabetes clinics throughout the country is to see whether it's possible to stop further loss of beta cells by giving a drug called rituximab to patients. Rituximab is to lower B cells.
The authors plan to measure whether the beta cells that are left when the drug is given at or before three months of T1DM continue to exist and produce insulin. They'll check hemoglobin A1c measurements and insulin doses. As of this writing, the results of this study are expected to be published very soon.
Another drug that's undergoing the same study is TRX4; the study is also being conducted by diabetes clinics throughout the country. The intention is to see if TRX4 can preserve or even improve beta cell function and reduce the amount of insulin that the patient has to take. Results should be available soon for this study as well.
One of the most exciting approaches that I've come across regarding T1DM is the work of Dr. Lijun Yang, an associate professor at the University of Florida College of Medicine. She's found that she can infuse a protein called recombinant Pdx1 into mice with T1DM and no beta cell function, and it both regenerates beta cells in their pancreas and turns liver cells into insulin-producing beta cells. The mice no longer have diabetes after this treatment, and the Pdx1 protein isn't toxic to the mice in substantial doses.
As of this writing, Dr. Yang is working on a study of humans with T1DM to see if she can accomplish the same thing in human volunteers. The patients will be given human Pdx1 protein. As of this writing, this study hasn't begun.
It remains to be seen whether the beta cells, however they're regenerated, will be subject to the immune rejection of the original beta cells that turned the patients into people with T1DM in the first place.
One approach to preventing further loss of insulin production in newly diagnosed patients with T1DM is suppression of the immune response that's destroying the beta cells. A group in Brazil took this treatment a little further, and their work was published in The Journal of the American Medical Association in April 2007.
The scientists began by obtaining stem cells, which are cells that haven't become any particular kind of cell like white blood cells or red blood cells, from each newly diagnosed patient with T1DM. (The stem cells were taken within six weeks of the patients' diagnoses.) The patients received a high dose of an immunosuppressive drug to prevent the immune response that's believed to cause the destruction of beta cells. Then the scientists gave the stem cells back to the respective patients.
Of the 15 patients who received this treatment, 14 became able to control their blood glucose without insulin for different lengths of time: one patient for 35 months, four patients for at least 21 months, seven patients for at least 6 months, and two patients who were late responders and were insulin-free for one and five months, respectively. Levels of hemoglobin A1c were maintained at less than 7 percent in 13 of 14 patients, and only one patient needed to resume insulin after a year.
As of this writing, a study going on at the University of Florida is using the stem cells found in umbilical cord blood to attempt to regenerate beta cells. Cord blood has the advantage of containing a large number of cells that decrease immunity.
The plan is to enlist 23 children with T1DM over the age of 1 whose parents had the foresight to store their cord blood at birth. The cord blood is infused back into the child from whom it was taken.
The study, which is to be completed by 2009, will determine if the cells in the cord blood can change into insulin-producing cells and/or provide immune tolerance that will permit regeneration of beta cells.
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All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.