Diabetes mellitus is a chronic disease that is becoming more prevalent worldwide. Diabetes causes high blood sugar, which is harmful to health. As of 2015, 30.3 million people in the United States, or about 9.4 percent of the population, had diabetes.
Unfortunately, more than 1 in 4 people with diabetes don’t know they have it. Having undiagnosed diabetes increases the risk of diabetes-related complications such as kidney disease, heart disease, amputations, and more.
Many people also have prediabetes, a condition where blood sugars are slightly elevated but not high enough to be considered diabetes. Having prediabetes is a significant risk factor for eventually developing type 2 diabetes. The U.S. Centers for Disease Control (CDC) estimates that up to 30% of people with prediabetes will develop type 2 diabetes within five years of their prediabetes diagnosis.
The majority of people with diabetes have type 2, which typically affects older adults and can be related to multiple known risk factors, including race, weight, and some lifestyle factors. Type 1 diabetes is more rare as it’s an autoimmune disorder.
It usually occurs before age 18, which is why it’s also referred to as juvenile diabetes. Type 1 diabetes affects about 2-5% of the world’s population or about 1 in 300 American adults before the age of 18.
Diabetes is a disease affecting the regulation of blood glucose (sugar) levels. An organ called the pancreas creates the hormone insulin, which helps keep blood sugar levels in a healthy range.
With diabetes, the pancreas either doesn’t make enough insulin, or the body doesn’t respond to it well. Without proper insulin function, blood sugar levels rise and can lead to health problems if left untreated.
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Islet cells & diabetes
Cells require sugar (glucose) for energy; glucose is the preferred energy source over other sources. Cells have insulin receptors, which insulin attaches to in order to let the sugar in. An easier way to think of it is that the cells have doors, the insulin receptors are the doorknobs, and insulin is the key to open the doorknob to allow sugar in to feed the cells.
Without enough insulin present, blood sugar builds up in the bloodstream as it is unable to enter the cells to provide energy. Prolonged high blood sugar can damage blood vessels and lead to numerous health problems such as heart disease, nerve damage, poor wound healing leading to amputations, and more.
The pancreas is the organ responsible for producing insulin. When the pancreas’ ability to produce insulin is impacted, diabetes results. The process cannot be reversed, which is why there is no cure for diabetes.
There are small clusters of cells in the pancreas responsible for creating hormones like insulin. These clusters of cells are called islets of Langerhans, or just “islets.” The islet cells are a relatively small part of the pancreas, making up only 1-2% of the mass of the pancreas. However, they receive 10-15% of the blood flow to the pancreas.
Islet cells are responsible for housing three major cell types, each of which creates its own hormone.
- Alpha cells or “A cells” secrete the hormone glucagon. Glucagon tells the liver to release its stored sugar (called glycogen) into the bloodstream to help prevent and correct low blood sugar (hypoglycemia). Glucagon and insulin have opposing effects on blood sugar and are important to keep blood sugar levels steady. Without glucagon, blood sugar levels could drop too low and cause severe hypoglycemia, a potentially dangerous medical situation. People on insulin sometimes carry glucagon injections in order to treat severe hypoglycemia.
- Beta cells or “B cells” produce the hormone insulin and make up the majority of the islet cells in the human pancreas. These cells are the most well-known for their role in diabetes since the destruction of beta cells can lead to diabetes. In type 1 diabetes, an autoimmune disease, the immune system mistakenly attacks the beta cells, so the pancreas no longer secretes enough insulin to keep blood sugar levels from rising too high.
- Delta cells or “D cells” create the hormone somatostatin, which inhibits the action of other hormones. For instance, a rare tumor called a somatostatinoma inhibits beta cells’ production, leading to diabetes.
Islet cell transplant vs pancreas transplant
An islet cell transplant surgery is an option for people with type 1 diabetes. Type 1 diabetes is much different than type 2 diabetes – it’s an autoimmune disease, whereas type 2 diabetes is not. People with type 1 diabetes often struggle to keep their blood sugar levels regulated despite treatment therapies like insulin pumps and continuous glucose monitoring.
Islet cell transplant surgery involves removing the islet cells of a deceased donor’s pancreas. The cells are then purified and transplanted into the islet transplant recipient’s liver.
Once in the recipient, the islet cells can start to produce endogenous (internally made) insulin, reducing or eliminating the person’s need for injecting exogenous (externally made) insulin. It can sometimes take up to three transplants for a patient to receive insulin independence, meaning their new islet cells produce enough insulin to help control their blood sugar levels.
Islet cell transplant surgery is being studied and used only for people with severe and progressive type 1 diabetes complications. It can only be done as part of an FDA clinical trial and is currently considered an experimental treatment in the United States. The Collaborative Islet Transplantation Registry (CITR) has reported that 1,086 people worldwide received islet cell transplants for type 1 diabetes between 1999 and 2015, making it a rare procedure overall.
Pancreas transplant: Another surgery aimed to help treat diabetes is a whole pancreas transplant. A pancreas transplant involves removing a pancreas from a deceased donor and transplanting it into the recipient.
A pancreas transplant is usually done in people with type 1 diabetes, though it can occasionally be done for people with type 2 diabetes. The reason it isn’t usually performed on people with type 2 diabetes is that they usually still have some functioning of their beta cells and their ability to produce insulin. In contrast, people with type 1 diabetes don’t have an adequate beta-cell function.
There are several types of pancreas transplants:
- Pancreas transplant alone. People with diabetes and early or no kidney disease may be candidates for a pancreas transplant alone (solitary pancreas transplant). A pancreas transplant surgery involves the placement of a healthy pancreas into a recipient whose pancreas is no longer functioning properly.
- Combined kidney-pancreas transplant. Surgeons often may perform combined (simultaneous) kidney-pancreas transplants for people with diabetes who have or are at risk of kidney failure. Most pancreas transplants are done at the same time as a kidney transplant.
- Pancreas-after-kidney transplant. For those facing a long wait for both a donor kidney and a donor pancreas to become available, a kidney transplant may be recommended first if a living- or deceased-donor kidney becomes available.
- After the patient recovers from kidney transplant surgery, they receive a pancreas transplant once a donor pancreas becomes available.
Pancreas transplants may be considered for situations such as:
- People with type 1 diabetes that cannot be controlled with standard treatment
- Frequent insulin reactions
- Consistently poor blood sugar control
- Severe kidney damage
- Type 2 diabetes associated with both low insulin resistance and low insulin production
Yet another surgery involving the pancreas is a total pancreatectomy followed by an autologous (auto-) islet transplantation. This procedure is usually used to treat chronic pancreatitis, a painful inflammation of the pancreas that can damage the organ. A pancreatectomy involves removing the entire pancreas, which resolves the pain from pancreatitis.
After the removal of the pancreas, the surgeon removes the islet cells from the diseased pancreas and transplants them into the individual via the liver, similar to a regular islet cell transplantation.
This complex procedure is usually reserved for instances when other treatment methods have failed. It isn’t typically a suitable surgery for people with diabetes because it requires functioning islet cells from the person having the pancreatectomy, which people with diabetes usually don’t have.
Benefits and risks of islet transplantation
The main benefits of islet cell transplantation are:
- Improvement in blood glucose levels
- Reduce or eliminate the need for insulin injections
- Better recognize symptoms of hypoglycemia (low blood sugar)
- Prevent severe hypoglycemia, which can result in coma and death if left untreated
Some of the risks of islet cell transplantation are involved with the body accepting or rejecting the transplanted cells. As with any organ transplant, there is a risk that the body will reject the donor organs/cells, which will make them no longer work.
To help reduce this risk, donor recipients are put on immunosuppressant drugs, which work to lower the immune system. This has its own risks since the immune system is meant to protect the body from harmful infections.
Some potential risks of islet cell transplantation include:
- Bleeding, blood clots, and pain
- A chance that the transplanted islets may not work well or may stop working
- Side effects of anti-rejection medicines
- Development of antibodies against the donor cells that may make it more difficult to find an appropriate organ donor if another transplant is needed in the future
Some risks associated with the use of immunosuppressant drugs include:
- Higher chance of getting infections
- Higher chance of getting cancer
- Digestive side effects, such as vomiting, nausea, or diarrhea
- Headaches, tremors, or confusion
- High blood pressure
- High blood glucose levels
- High levels of cholesterol and triglycerides in the blood
- Kidney damage
Advancements in diabetes treatment
Research in diabetes treatment is ongoing, intending to make treatments more effective and therefore improve the health and wellbeing of people impacted by diabetes. Some more recent diabetes treatments in the last couple of years include:
- Semaglutide (Rybelsus) is a medication in the class of medications called GLP-1 receptor agonists. It’s unique because it is the first oral medication in its drug class delivered orally versus an injection. Rybelsus was approved in 2019.
- Glucagon (Baqsimi) nasal powder was approved in 2019 as the first glucagon treatment in powder form. Usually, glucagon is administered as an intramuscular injection. It is administered in the case of severe hypoglycemia, especially if the individual suffering from hypoglycemia is too confused or is unresponsive and is unable to consume carbohydrates to help correct the low blood sugar. Baqsimi is approved to treat severe hypoglycemia in people ages 4 and older.
- Continuous glucose monitors (CGM) – the first CGM was approved in 1999, but there have been many CGM technology advancements in recent years. CGM devices automatically measure blood glucose levels every 5-15 minutes using a sensor under the skin and transmit the data to a receiver. This provides a more detailed and comprehensive picture of blood glucose trends.
Conclusion
The pancreas is an organ responsible for producing insulin as well as other hormones important for blood sugar regulation. In diabetes, the pancreas loses some or all of its ability to create insulin, leading to high blood sugar levels.
The pancreas has groups of cells called islet cells, which are further classified into alpha-, beta- and delta- cells. Beta cells produce insulin, and alpha cells produce glucagon. Both of these hormones are vital for the regulation of blood sugar levels.
An experimental treatment being studied is islet cell transplantation, where islet cells from a deceased donor pancreas are transplanted into the recipient. The goal of the islet cell transplant is that the recipient will have restored endogenous (internal) insulin secretion, therefore reducing the need for exogenous (external) insulin treatment.
Islet cell transplantation is only allowed in the United States as part of an FDA-approved clinical trial and is considered experimental. Worldwide, there have been fewer than 2000 islet cell transplants performed between 1995 and 2015.
Another potential treatment for diabetes is a pancreas transplant, which is usually used for people with type 1 diabetes but can be used for type 2 in rarer circumstances.
There are constant advancements in diabetes treatments and technology. Diabetes treatment research is ongoing with the goal of improving the health and wellbeing of people impacted by diabetes.
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