The Future of Diabetes

Stem Cell Research
Tissue Engineering
Islet Transplants
Gene Research
Artificial Pancreas
Twin Epidemics

Perhaps because so many more people are developing diabetes today than in the past, the search for ways to better control it, even to cure it, is being pushed even harder. In recent years diabetes care has improved tremendously because of ongoing research, new medicines, and increased knowledge about how to manage it. In addition, many people with diabetes now receive not only better medical care but counseling and emotional support not available in the past.

What does the future hold for people with diabetes? Someday, they may be able to give up injecting themselves with insulin and instead breathe it in through an inhaler, take it in a pill, or absorb it through their skin from an insulin patch. Pricking a finger to get a blood sample for a glucose reading may one day be a thing of the past, as new devices are being developed for this process. One new product now under consideration but far from actual development is called the Charmr. This small electronic device would look like a tiny iPod. It could be worn on a neck chain or around the wrist like a watch, and it would replace both the bulky insulin pump and the glucose testing meter.

Many researchers are investigating several possible new treatments for diabetes. The list includes stem cell research,

tissue reengineering, islet transplantation, gene research, and development of an artificial pancreas.

Stem Cell Research

Embryonic stem cells are immature cells in animal embryos that later develop into other cells that make up all the various organs and tissues of the body, such as the heart, eyes, lungs, bones, and pancreas. Early in their development they are like blank slates, but then a process happens in the embryo to make them begin changing into those different kinds of cells. No one understands this entire process yet or how to reproduce it in the laboratory. Adults also have stem cells, but they work differently from embryonic stem cells, and they are not used for the same kind of research.

An enormous amount of research has already been done with the pancreas. Scientists have identified the “master” genes in this organ, and some of these master genes tell embryonic stem cells to become beta cells, which create insulin. Once scientists discover how to re-create this very complex process in the lab, they can then build a process to safely and reliably manufacture enough beta cells. Someday these manufactured cells could possibly be used to cure type 1 diabetes. People with type 2 might also be able to use them for better control of their illness.

Tissue Engineering

Tissue engineering is an amazing process that scientists recently developed to help replace damaged parts of the body. Someday they hope to be able to grow various organs, even hearts and lungs, in the lab for people who need transplants. However, tissue engineering is still very new, and skin is about the only body part that so far can be successfully engineered in a lab for use in humans.

Engineered skin is made by taking skin cells from a person who, for instance, has suffered severe burns and cannot re-grow enough of his or her own skin naturally to cover the burned portions. Those skin cells are used to grow pieces of new skin in a special lab. The new skin can then be grafted over the burned areas and help them heal.

It is common for people with diabetes to have cuts or wounds on their feet that do not heal, even after many months of treatment, because their illness damages the skin of the feet and legs. These wounds can become seriously infected, which can lead to amputation. It has been found that tissue-engineered skin can be used to help these wounds heal. Unlike the skin used for some burn victims, this new skin is made from tissues other than the patient's, but it works very well. The doctor carefully cleans the wound and then places the tissue-engineered skin over it. It grafts with the person's own skin, and the body restores the injured area. Treating these wounds with tissue-engineered grafts promotes faster healing more often than the usual treatment with moist dressings.

It is also less risky and less expensive than taking live skin from a donor.

Tissue engineering also presents many opportunities for researchers looking for improved diabetes treatments or a cure. They believe that beta cells can eventually be tissue-engineered to replace the damaged or missing ones in the pancreas of a person with type 1 diabetes. These cells would be placed into the person's pancreas, where they could grow and reproduce to make adequate amounts of insulin once again.

Large-scale research in this area faces one large obstacle, though. Many millions of beta cells are needed for this research, along with a continuing supply for many years. But not enough beta cells are available to researchers (these cells come from deceased human donors). Furthermore, those donor cells that have been available have not been able to survive or maintain their ability to produce insulin in the lab for very long.

However, some of the scientists doing this research have been able to produce a “cell line” of beta cells, similar to lines of stem cells, that has shown promising results for tissue engineering. These specially created cells would be an excellent and abundant alternative to donated cells. When they were tested in diabetic mice in 2005, the new beta cells controlled the mice's blood sugar levels for just over four months and produced about 40 percent as much insulin of normal beta cells. Although these results were not permanent and need improvement, this is an excellent outcome for an early experimental treatment. However, for such a treatment to be fully tested and declared safe for humans will take years.

Islet Transplants

The islets of Langerhans are clusters of cells in the pancreas that contain beta cells, which make insulin. In a medical procedure that is still experimental, these islets are carefully removed from a deceased person's pancreas and transplanted into the pancreas of a person with severe type 1 diabetes. The results are promising but by no means perfect. “The ultimate goal of islet cell transplantation is to normalize blood glucose

levels and prevent secondary complications of diabetes, such as kidney failure, heart disease, nerve damage and loss of vision,”³⁸ says Alan C. Farney, a transplant surgeon at the University of Maryland Medical Center.

In one study in Canada, sixty-five people with type 1 diabetes that was difficult to control received islet transplants. Five years later, only about 10 percent of those people no longer had to inject insulin. Most of the other people had to begin using insulin again after the transplanted islets gradually lost their ability to make their own. However, many of these same people had been able to reduce their use of insulin, have more stability in their levels of blood glucose, and reduce problems with hypoglycemia, or low blood sugar.

In another study of 225 patients from the United States, Canada, Europe, and Australia who received islet transplants, nearly two-thirds were able to stop injecting insulin for at least two weeks at a time during the first year after the operation. However, that number fell to only one-third two years after the surgery. Even so, many of the 225 people still required less insulin than before the transplant, had improved control of blood glucose, and greatly reduced their risk of becoming severely hypoglycemic.

However, says Farney, the islet transplant “is not a cure. It is a treatment. Patients will still have to take medicine to prevent rejection of the transplanted cells.”³⁹ As with any transplant, rejection is the greatest risk and problem. When the body senses something inside it that it believes does not belong there, the immune system will attack it in an effort to get rid of it. With type 1 diabetes, the immune system often mistakenly destroys the person's own beta cells, and this can happen again with new islets from someone else.

That is why people who receive any kind of transplant, including islets, must take special drugs, called immunosuppressive drugs, to prevent the body from attacking and destroying the transplanted islets. These drugs must be taken for life. Unfortunately, these drugs can have terrible side effects, including mouth sores, digestive problems, anemia, and high blood pressure and cholesterol levels. Because they suppress the immune system, they make the person more likely to have infections, and

they also increase the risk of cancer. Therefore, people who undergo islet transplantation must first understand the possible severe side effects. Researchers are continuing to look for new and better immunosuppressive drugs with fewer side effects. Their main goal is to help people who receive islet transplants to achieve immune tolerance, which would enable them to keep the new islets functioning normally without all the drugs.

As islet transplants become safer and more common, more people with type 1 diabetes will want to have the surgery. However, a great shortage of donated pancreases prevents more of these surgeries from being done. Researchers are looking for solutions to this problem, too. One possibility is to use a portion of a pancreas from a living donor, rather than from a deceased one. Not enough pancreases to meet the need are donated after death, so the hope is to find more living donors. Researchers have also experimented with injecting pig islets into other animals. Since pig organs are very similar to humans’, the researchers are hoping to someday use pig islets as an abundant source for human transplants. Perhaps islet cells could also be created from stem cells or other kinds of cells, and then they could be grown in a lab.

Gene Research

Both types 1 and 2 diabetes have their roots in a person's genes, which carry DNA, or the basic building blocks of an organism, from one generation to the next. Half of a person's genes come from the mother and half from the father, and human beings have tens of thousands of them. Genes determine if people have blue or brown or green eyes, how tall they are, if they go bald, if they have the potential to develop various illnesses, and so on.

To complicate matters, just because a person has a gene linked to a certain disease, that does not mean the person will eventually develop the disease. For instance, if someone has the genes related to type 2 diabetes but maintains a healthy weight and gets enough exercise throughout his or her life, the disease may never appear.

The study of genes is still very young, so scientists still have much to learn about the human genome, or the full collection

Bones and Diabetes

A research study in 2007 showed how bones make a hormone that helps to regulate sugar and fat in the body. The scientists who did this research with mice are hopeful that this breakthrough might one day lead to a treatment or even prevention of type 2 diabetes in humans.

According to Gerard Karsenty, the lead author of the study, “What this study shows is that [the skeleton] is a lively organ that has a function to regulate the biology of the other organs in the body, such as the pancreas and insulin secretion, and fat and insulin sensitivity.… It is the first time the skeleton has been shown to reach out to other organs in the body.”

The scientists doing this research discovered that cells that form bone, called osteoblasts, release a hormone called osteocalcin, which helps the body produce more insulin and increases insulin sensitivity. Osteocalcin also pumps up the number of beta cells in the pancreas that produce insulin while reducing fat.

It will likely be ten or fifteen years before research can show that this kind of hormone injection would be safe for humans. In the meantime, Karsenty recommends that everyone, especially people with diabetes, take care of their bones.

of human genes. But one thing they do know is that diseases, including diabetes, are usually caused by multiple genes. Perhaps diseases would be easier to cure if only one gene was responsible.

Janelle Noble is a researcher at Children's Hospital Oakland Research Institute who is building a genetic database of children and families with diabetes. At a meeting of diabetes experts in 2008, she said, “If we're going to prevent diabetes we have to know who's likely to get it in the first place. But looking for variants of genes that cause complex diseases is like looking for a needle in a haystack.”⁴⁰

Research also suggests that many more varieties of diabetes than types 1, 2, 1.5, and gestational may exist. If this is the case, then the genetic basis for diabetes will be even more complicated than previously believed, and treatment could be much more personalized than it is today. Many researchers studying this are investigating questions such as, of two equally over-weight people why does only one have diabetes? Or, why do some diabetics still have healthy kidneys even after decades of poor blood sugar levels, while others’ kidneys are terribly damaged early on?

A gene therapy developed at Baylor College of Medicine seems to have cured diabetes in mice by coaxing their liver cells to become beta cells that produce insulin. The mice were completely cured of diabetes for at least four months. Since the liver cells came from the mice themselves, antirejection drugs were not needed. While it will be many years before this procedure can safely be used in humans, it is a very promising development.

Artificial Pancreas

An artificial pancreas would revolutionize diabetes treatment. By automatically regulating a person's blood glucose, such a device implanted under the skin would allow type 1 diabetics to keep their levels within a normal range.

Scientists are already developing an artificial pancreas and are having some success, although it is not yet ready for widespread use. This human-made pancreas has three parts: a sensor

to continually monitor blood glucose, an insulin pump, and a small computer that controls insulin delivery.

Insulin pumps are already in common use. The most difficult part of the device to make is the glucose sensor. None made so far offer consistently accurate results.

Space Age Implantable Insulin Pumps

In 1986 Sam Zaccari, now almost seventy, had one of the first implantable insulin pumps surgically placed inside his body. In 1998 he said, “It's wonderful because without this technology that we got today I wouldn't have the control I have and maybe I might not be here.”

Zaccari's insulin pump, made of titanium, was developed in part from the technology of the mechanical robot arm of the first space probe sent to Mars. The pump had a similar design to the portion of the arm the Viking spacecraft used to touch the Martian soil for experiments.

Zaccari's pump was computerized and allowed him to have more precise control of his blood glucose. He knew how important this control was, since his mother, brother, and sister had died from the complications of their diabetes. Having his pump meant he could live a more normal life and avoid their fate. Today, this Baltimore resident, nicknamed the Iron Man for his strength and longevity, still takes daily walks and has raised hundreds of thousands of dollars for diabetes research. He believes he could not have done this without his implantable insulin pump.

Quoted in Dan Rutz, “From Pacemakers to Braces, the Medical Benefits of Space Exploration,” CNN, November 2, 1998. www.cnn.com/HEALTH/9811/02/space.medical/index.html.

An artificial pancreas began undergoing tests in France in 2003. The sensor is placed in a neck vein, and it communicates with the implantable pump in the abdomen by using a wire under

the skin. The pump then releases the right amount of insulin.

Results were good, with the device automatically keeping the person's blood sugar in the normal range more than half the time (although this needs to be improved) and with the risk of hypoglycemia falling to under 5 percent. The biggest problem is that the sensors stop working inside the body after about nine months and have to be replaced. This means the person using it has to undergo minor surgery again every time a replacement is needed. The sensor needs to be made out of better materials that can withstand the environment inside the body, so scientists are working on that. They believe that a safe, workable artificial pancreas will be available within the next few years.

Twin Epidemics

Diabetes is a growing problem in the United States. That growth is intertwined with the increase in the number of individuals who are seriously overweight or obese. Many factors in society have brought about these twin epidemics, the largest ones being unhealthy diets and lack of physical activity. So, even though people must take responsibility for their own health, that is a difficult task without support from the larger society.

Modern medicine is developing new techniques that may someday make diabetes more manageable and easier to live with. Perhaps researchers will even find a way to reduce or stop the terrible complications of diabetes. Yet whatever miracles medicine may someday produce to help people with diabetes, there is one sure way to end this epidemic. Society must focus on helping everyone to have a healthy, balanced diet and to get adequate amounts of physical activity so that their bodies can perform in the wonderful way they were designed to.