Type 1 Diabetes

(also known as childhood- or juvenile-onset diabetes – typically affects children and young adults)

Type 1 diabetes develops when the body’s own immune system starts to attack and destroy the beta cells of the pancreas. Without these cells, the body cannot produce insulin, a hormone essential for converting glucose (sugar) into energy. Without enough insulin, too much glucose is left in the bloodstream, which can lead to long-term damage to the kidneys, eyes, nerves, heart and blood vessels.

Type 2 Diabetes

Type 2 diabetes is slightly different from type 1, although the potential for l ong-term damage remains the same. With type 2 – which generally affects sedentary and overweight adults – instead of the immune system attacking the beta cells, the body gradually becomes unable to produce enough insulin for good health.

About 10 per cent of people with diabetes have type 1; about 90 per cent have type 2.

Today, more than 250 million people worldwide are 

living with diabetes. Approximately seven million people each year – or two people every 10 seconds – develop the disease. By 2025, more than 380 million people may be affected.

Diabetes UK reported that 2.6 million people in the UK were diagnosed with diabetes by 2009. By 2025 they expect that more than four million people will have been diagnosed in the UK. It is estimated that there are up to half a million more people in the UK who have diabetes but have not been diagnosed.

Together, type 1 and type 2 diabetes are the world’s fourth leading cause of death.

A recent U.S. study estimates that someone dies of diabetes-related causes every 10 seconds. In Scotland  death rates for adults with diabetes aged 20 and older are two to three times greater than those of the general population. Approximately 10 to 20 per cent of people with diabetes die of kidney failure, while about 50 per cent of people with diabetes die of heart disease and stroke.

In addition:

•  Diabetic retinopathy is an important cause of blindness, and occurs as a result of long-term accumulated damage to the small blood vessels in the retina. After 15 years of diabetes, approximately two per cent of people with diabetes become blind, and about 10 per cent develop severe visual impairment.

•  Diabetic neuropathy is damage to the nerves as a result of diabetes, and affects up to 50 per cent of people with diabetes. Common symptoms of diabetic neuropathy are tingling, pain, numbness, or weakness in the feet and hands. Combined with reduced blood flow, neuropathy in the feet or hands increases the chance a person with diabetes will eventually lose an arm or a leg.

Scientists do not know exactly what causes type 1 diabetes, but believe it may be caused by a combination of genetic factors and environmental stressors, such as a virus.

Symptoms of type 1 diabetes include increased thirst, frequent urination, constant hunger, weight loss, blurred vision and extreme tiredness. If the condition is not diagnosed and treated in time with insulin, a person with diabetes could lapse into a life-threatening coma.

Unlike type 2, type 1 diabetes cannot be prevented or managed through changes in lifestyle, such as exercising more and eating healthier foods.

Insulin Injections

The vast majority of people with type 1 diabetes (and about one-third with type 2) must both test their blood sugar and inject themselves with insulin at least four times a day.

However, while these injections can help people with type 1 diabetes to maintain and balance their blood sugars, they do not cure diabetes or prevent long-term damage to the body. And, because a person’s blood sugar can fluctuate for many reasons – including food intake, hormonal changes, growth periods, infections and even emotions – diabetes is especially challenging to manage in children.

Pancreas Transplants

A small number of people with type 1 diabetes – about 1,300 a year in the United States, for example – receive whole-organ pancreas transplants to treat the disease. After one year, 83 per cent of these patients, on average, show no symptoms of diabetes and do not have to take insulin to maintain normal blood sugar levels.

But this treatment is not widespread, for two primary reasons: the limited availability of organs to transplant, and the fact that, to prevent the body from rejecting the transplanted pancreas, recipients must take powerful drugs to suppress their immune systems for the rest of their lives, which leaves them susceptible to a range of other diseases. Many doctors feel that the immunosuppressant therapy could be a greater health threat than the diabetes, and will only do a pancreas transplant if the patient also needs a kidney transplant and would require immunosuppressant drugs anyway.

Islet Cell Transplants

Recently, doctors have attempted to cure diabetes by injecting patients with pancreatic islet cells, which are made up of several types of cells, including the beta cells that produce insulin. In this procedure, doctors use special enzymes to separate the islets from the pancreas of a deceased donor, then inject them into the patient’s liver. Once implanted, the beta cells in these replacement islets begin to make and release insulin.

This procedure is easier and safer than the major surgery of a pancreas transplant. However, like those who receive pancreas transplants, these patients also require powerful immunosuppressant therapy to (1) prevent their bodies from rejecting the foreign cells, and (2) prevent their immune systems from attacking and destroying these replacement cells as they did the originals. The traditional, steroid-based anti-rejection drugs, in addition to leaving patients susceptible to other diseases, also have a negative effect on insulin-producing cells and eventually may exhaust the cells’ ability to produce insulin.

To try to overcome these challenges, a group of researchers at the University of Alberta in Edmonton developed an experimental protocol that uses both a larger amount of islet cells and a different type of immunosuppressant therapy. In 2000, the group reported that seven of seven patients who received islet cell transplants no longer needed to take insulin and their blood glucose levels were normal a year after surgery. In 2005, the researchers published results for 65 patients and reported that about 10 per cent remained free of the need for insulin injections after five years. Most recipients, however, returned to using insulin because the transplanted islets lost their ability to function over time.

Other long-term studies have confirmed that, while an islet cell transplant can restore the body's ability to produce insulin, it does not result in permanent independence from insulin injections. But even without insulin independence, the ability to produce at least some insulin does make it easier to control blood sugar levels and greatly reduces the risk of severe hypoglycemia (too little blood sugar). And, because good control of blood glucose can slow or prevent the progression of complications associated with diabetes, a successful transplant may reduce the risk of heart disease, kidney disease and nerve or eye damage.

Unfortunately, while these results are positive, several major difficulties remain. In addition to the fact that islet transplant patients still require lifelong immunosuppressant therapy, one islet cell transplant treatment currently requires two donor organs, which are in very short supply. These donor organs must also be compatible with the patient, and must be used within about 18 hours.

Researchers continue to explore the use of new anti-rejection therapies and to look for possible alternative sources for islets or beta cells, including stem cells, that would enable scientists either to:

• increase the supply of beta cells from donor organs, which would increase the number of transplants doctors are able to perform,

or

• avoid the use of donor organs entirely by using a patient’s own cells and either convincing existing beta cells to reproduce or reprogramming other types of cells to become beta cells.

Because stem cells have the potential to grow into any one of the body’s more than 200 cell types, diabetes researchers have been searching for decades for methods to isolate stem cells – adult and embryonic – and program them to become insulin-producing beta cells.

Adult Stem Cells

Dr Joel Habener of Harvard Medical School and his colleagues have identified islet-like stem cells from adult pancreatic tissue that they think could be encouraged to differentiate into insulin-producing beta cells.

In a separate research stream, scientists at the Robarts Research Institute in London, Ontario, successfully used adult bone marrow stem cells to reduce high blood glucose and raise insulin levels in mice. The bone marrow stem cells – injected into the bloodstream – did not themselves become beta cells, but rather triggered new beta cell growth in the recipient’s pancreas.

One adult stem cell procedure has moved beyond trials with mice to testing on people.

In the first trial of autologous nonmyeloablative hematopoietic stem cell transplantation by a joint Brazilian and American team in 2007, 14 of 15 patients – all recently diagnosed with diabetes – achieved insulin independence for periods ranging from one to 35 months. With AHST, doctors first give the patient high-dose immunosuppressant therapy, then remove the patient’s own stem cells, treat them so that they become insulin-producing beta cells, and return them to the patient. Further tests of this procedure are ongoing.

Embryonic Stem Cells

Using different techniques, experiments around the world have established successful methods for converting both mouse and (in 2008, by stem cell engineering firm ViaCyte, Inc., of San Diego) human embryonic stem cells into insulin-producing cells in mice. With both types of embryonic stem cells, the replacement stem cells kept blood sugar in check after the mice’s own insulin-producing cells were destroyed. It will, however, be several years before tests on humans can begin.

Because diabetes is well understood and islet transplants have already been identified as an effective treatment – where a relatively simple transplant procedure of just a teaspoon of cells has been shown to work and the patient can go home the same day – it is a prime candidate for stem cell research. In theory, the cells can be transplanted virtually anywhere in the body, and will still function.

At the same time, however, type 1 diabetes may prove to be especially difficult to cure, because beta cells are destroyed by the body's own immune system. Researchers must find a way to overcome this auto-immunity in order to make transplants possible without the immunosuppressant therapy that can be more damaging than the cure for many patients with diabetes.

While other kinds of cell-based research could all potentially lead to an unlimited supply of insulin-producing cells ready for transplantation, embryonic stem cell research may offer the best hope for avoiding the possibly devastating effects of immunosuppressant therapy, because researchers currently believe that embryonic stem cells may be naturally less likely to be rejected, or could be more easily engineered to avoid immune rejection.

Research is also continuing into other ways to transplant islet cells without immunosuppressant therapy. One study, for example, is testing the effectiveness of encapsulating islets in a special coating designed to prevent rejection. This coating would allow the islet’s beta cells to secrete insulin into the bloodstream, but remain inaccessible to the immune system.

Other diabetes research is concentrating on islet cell regeneration without transplantation; developing a blood test that could identify whether a person is going to develop diabetes; and imaging techniques that would allow scientists to look inside the body to find out how well an islet transplant or cell-regeneration therapy is working.

Our thanks go to the Stem Cell Network in Canada for their work on this information