Transplantation in type 1 diabetes

Transplantation in type 1 diabetes

Transplantation in type 1 diabetes

The gold standard in the treatment of type 1 diabetes patients represents the intensified insulin therapy or the insulin Pump therapy (CSII). Thanks to modern Analog insulins, In many cases, good blood glucose control is now possible thanks to innovative technical aids, good training and patient care. Heavy hypos (hypoglycemia) and late effects of diabetes can often be avoided.

Nevertheless, there are patients with Type 1 Diabetes, which despite optimal diabetes management does not achieve a satisfactory treatment result. A – fortunately small – critical group of sufferers suffers over and over again heavy hypoglycaemia and complications, which lead to a limited quality of life up to the inability to work.

Reasons for difficult-to-adjust diabetic metabolism may include:

  • A long diabetes duration.
  • Often very low insulin requirements.
  • Strong fluctuations in insulin action and sugar reabsorption from the gut.
  • Diabetes-related damage to the autonomic nervous system (autonomic neuropathy). This can affect various organs, such as the stomach or intestine, or even with a disturbed hormonal counterregulation associated with declining blood sugar. Hypoglycaemia is then perceived worse (hypoglycaemia perception disorder).

For patients with Type 1 diabetes, Those who fail to achieve sufficient metabolic control with conventional insulin therapy are facing the urgent question of alternative treatment options.

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Beta cell replacement therapy as an alternative treatment option

An interesting approach to alternative treatment options in type 1 diabetes is to replace the insulin-producing beta cells lost in the pancreas with autoimmune disease type 1 diabetes. The goals are:

  • To restore the body’s own insulin secretion, which, like in a healthy body, is regulated by the level of blood sugar.
  • Avoidance of acute emergency situations due to hypoglycaemia or hyperglycemia.
  • Improving the quality of life.
  • The avoidance of diabetes-related long-term consequences.

Two methods of beta cell replacement therapy are available today:

  • The Organ transplantation of the complete pancreas (pancreas) a donor or
  • the Islet cell transplantation.

For an islet cell transplant, the Langerhans cells are first obtained from a donor pancreas. These are the cell areas in which the insulin-producing beta cells are located. This tissue is prepared in the laboratory and flooded through a catheter into the portal vein of the patient’s liver. There they settle as a kind of miniature organ and start insulin production.

Transplantation of a pancreas or islet cell transplantation?

The prerequisites that patients must bring with them to be suitable for one or the other method are similar. Late complications can be avoided more successfully in both methods. However, the forms of therapy differ significantly in terms of the size of the required surgical procedure and associated risks:

  • The Transplantation of a pancreas is a relatively large surgical procedure that, like all surgeries, involves certain risks (e.g., bleeding, infection, after-effects of anesthesia, etc.). Frequently, additional operations will be necessary in the further course. There is an age restriction for this transplant (about 50 years). A very critical assessment of concomitant and sequelae is crucial.
  • The Islet cell transplantation however, it is a little invasive and the complication rate is very low. The islets are introduced into the portal vein of the liver either via a minimal abdominal incision (mini-laparotomy), or through a targeted liver puncture (an ultrasound-guided small puncture into the organ). Therefore, there is no basic age restriction for this form of transplantation. Concomitant diseases are less critical.

Transplantation – both of the pancreas and islet cells – leads to the lifelong use of immunosuppressive drugs.

In order to avoid rejection reactions, drugs must be taken after both interventions that suppress the normal function of the immune system (immunosuppressants). There are a number of modern, effective drugs available for this purpose. However, these are associated with relevant side effects. A careful benefit-risk assessment is therefore crucial.

Successes of islet cell transplantation

The long-term results after islet cell transplantation have steadily improved over the last few years, mainly due to the refinement of the method for cell production and the concomitant medication used. Today, in the majority of patients over ten years, a good organ function can be achieved. However, those treated are not completely independent of Insulin Syringes. Insulin independence depends on the total transmitted mass of islet cells.

Globally, in many centers, islet cell transplantation is often performed in stages, with up to three preparations of multiple donor islands. This significantly improves insulin independence. The results are comparable to those after pancreatic organ transplantation (pancreas transplantation).

After an island cell transplant, insulin usually still needs to be injected. However, the blood sugar metabolism stabilizes and complications are avoided.

However, in countries such as Germany, where donor organs are in short supply and access to donor pancreas is limited for islet cell transplantation, this multiple transplantation procedure can not be implemented. Instead of a complete insulin independence, the treatment goals of an islet cell transplantation in Germany from the outset rather

  • an insulin secretion that is sufficient to stabilize blood sugar levels, as well as
  • the prevention of hypoglycaemia (hypoglycaemia).

These therapeutic goals are usually achievable with a single transplant and the correspondingly treated patients benefit very well. From a patient’s perspective, the benefits of the treatment outweigh, even if insulin must continue to be supplied from outside.

Carefully consider islet cell transplantation

Although the mechanisms have not been fully elucidated, patients undergoing islet cell transplantation recover metabolic processes, which, in addition to insulin secretion, are also important for blood sugar regulation. These processes are immensely important to avoid diabetic emergencies and can significantly improve the quality of life of those affected.

Overall, islet cell transplantation accounts for a small proportion of people Type 1 diabetes mellitus, labile Sugar metabolism and frequent hypoglycaemia or hypo-perception disorders is a promising treatment option. The key treatment goal is primarily to stabilize the blood sugar control by restoring autonomous insulin release. For the success of the treatment, it is crucial to select the patients carefully, after all conventional treatment methods have been exhausted. Patients and treating physicians should conscientiously balance benefits and risks.

Bioreactors and animal islet cells: alternative transplant options

The search for alternative sources of beta cell replacement therapy is the focus of diabetes research worldwide. Have gained in importance

  • the Stem Cell Researchsuch as
  • the xenotransplantation (xeno- = foreign, gr.) So the use of animal donor cells.

In addition to numerous working groups worldwide, a research team from the University of Dresden is working on a system for the so-called macroencapsulation of islet cells. The graft will be integrated into a “container”. The challenge is to ensure a sufficient influx of oxygen and nutrients as well as an unimpeded outflow of the hormones insulin and glucagon. It is also important to maintain a safe barrier to the immune system to prevent rejection.

The “charm” of these systems lies in the relatively simple implantation technique. Two layers of islet cells embedded in alginate are encapsulated in a plastic housing.

In addition, the container contains a central oxygen tank, which can be filled from the outside, thereby ensuring optimal oxygenation of the islet cells. The capsule is surrounded by membranes, which on the one hand allow the exchange of glucose and insulin, but on the other hand shield immune system components from the transplant. The current version of this container is almost seven inches in diameter and 18 millimeters thick and is placed under the abdominal skin from the outside on the peritoneum, without opening the abdominal cavity.

The most recently published data of the working group around PD Dr. Ludwig describe the testing of encapsulated porcine islet cells in a model experiment. Both the safety and the effectiveness of the system were rated very positively. This provides the basis for a first clinical trial of the concept in humans.

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Christina Cherry
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