An overview

Nearly 400 million people worldwide are living with diabetes, and that number is expected to jump to almost 600 million by 2035, according to the International Diabetes Federation. For many people, diabetes can be controlled with diet, exercise and, often, insulin or other drugs. However, complications from diabetes can be serious and include kidney failure, nerve damage, vision loss, heart disease and a host of other health issues.

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What is diabetes?

At its most basic, diabetes is a condition in which the body cannot regulate or properly use sugar (called glucose) in the blood. The pancreas, which helps the small intestine digest food, has hundreds of thousands of cell clusters called islets of Langerhans where beta cells live. Beta cells produce insulin, which is released into the bloodstream when blood sugar levels reach a certain threshold. The insulin signals other cells in the body to take up sugar, the primary energy source for all the body’s cells.

  • Type 1, also known as juvenile diabetes. In type 1 diabetes, the body’s immune system attacks the beta cells in the pancreas. When the beta cells are damaged, they don’t produce insulin, or at least not enough insulin. Other cells never get the signal to take up sugar, so they don’t get the energy they need to function properly, and high sugar levels in the blood end up causing damage to the kidneys, eyes, nervous system and other organs.
  • Type 2 diabetes, also called adult-onset diabetes. In type 2 diabetes, cells in the body become resistant to insulin. They don’t respond to the signals insulin sends out, so they don’t take up sugar from the blood. The beta cells produce more insulin to signal the other cells, but eventually are not able to compensate. As with type 1, high blood sugar levels in type 2 diabetes can cause serious damage to the body.

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How is diabetes treated?

Type 1 diabetes patients are given insulin to help process sugar. However, they often have either high blood sugar or high insulin levels. They struggle to maintain the optimal balance found in healthy bodies and need to monitor their blood sugar several times a day. The advent of the insulin pump has greatly improved treatment for some people, enabling the delivery of individualized doses or a steady stream of insulin, but it cannot precisely mimic the healthy human body’s constant, sophisticated monitoring and adjusting of insulin production and blood sugar levels.

Type 2 diabetes can sometimes be controlled with diet and exercise. However, many people with type 2 diabetes eventually have to take insulin injections to control blood sugar levels and/or other medications to deal with complications from the disease

Since 1999, several hundred people with type 1 diabetes have received islet transplants. Many of these people have been able to stop taking insulin for at least a few months or years. However, most patients have to begin taking insulin again within four years after the procedure, and the procedure is complicated and still evolving.

Transplants generally are less effective in type 2 diabetes patients because they do not address the body’s resistance to insulin.

How are we using stem cells to understand diabetes?

Stem cells are helping us to explore the intricate way in which our bodies process sugar and to answer some important questions about the root causes of diabetes:

  • In type 1 diabetes, why does the immune system begin to attack beta cells and not other cells in the pancreas or in other organs or tissues?
  • In type 2 diabetes, what causes the resistance to insulin?

Stem cells are being used to create new cell culture and animal models of diabetes that better reflect what happens in a human. As one example, skin cells from a person with diabetes can be reprogrammed into induced pluripotent stem (iPS) cells that have the potential to make any cell type in the body, including beta cells, as well as the immune cells that attack and destroy beta cells in type 1 diabetes. The cell types involved in diabetes – the beta and immune cells – are being studied in the culture dish, as well as transplanted into lab animals.

This enables researchers to track the disease from the very earliest stages, before the point when diabetes is usually picked up in a patient. This helps us better understand what happens, what the genetic causes may be and to identify differences and similarities between different patients. Armed with this information, researchers look for ways to diagnose people earlier, prevent their diabetes from getting worse, and to more effectively treat the disease.

What is the potential for stem cells to treat diabetes?

Developing and testing a truly effective stem-cell based treatment for diabetes will take years. Researchers are looking at ways to restore the number of functional beta cells in patients with diabetes, pursuing both the replacement of lost beta cells and the protection of beta cells from further damage.

The first part of this is to generate—or regenerate— cells that sense glucose and produce insulin that might ultimately be used to replace the beta cells lost as both type 1 and 2 diabetes progresses.  Several different approaches are being used, including:

  • Making beta cells from embryonic stem cells or iPS cells. Embryonic stem cells and iPS cells can be grown in large number in the laboratory and have the potential to be coaxed into becoming any cell type in the body, including glucose sensing, insulin-producing beta cells. Recent leaps forward in these technologies make this a very promising avenue for generating large numbers of replacement beta cells.
  • Stimulating beta cells to make many more copies of themselves. Beta cells can do this in the pancreas, but usually very slowly, and less and less as we get older. Researchers are looking for drugs that might enhance this self-renewal as a possible treatment for people with type 2 or early-stage type 1 diabetes.

Key to these approaches is getting beta cells into a place in the body where they can work and protecting them from what was damaging them in the first place. This includes transplantation into parts of the body where the replacement cells are less likely to be attacked by the immune system or placement of the cells into protective capsules. Such capsules are porous and would allow small molecules such as glucose and insulin to pass through while protecting the beta cells from the cells of the immune system.

For type 1 diabetes, there are a number of experimental approaches being taken to curb the immune system’s attack on the beta cells. Most of these are still being explored in the lab. There are some clinical trials underway to test whether blood stem cells or mesenchymal stem cells from the bone marrow might alter or re-set the immune system so that it no longer attacks the beta cells. However, the mechanisms underlying how this use of these cells would work are not well understood, and further research is needed to establish whether any of these approaches will prove safe and effective.