FREQUENTLY ASKED QUESTIONS ABOUT THE ISLET TRANSPLANT

1. What is diabete?

Diabetes is a chronic disease, characterized by a dysfunction of the pancreas, more specifically of the Islets of Langerhans, the insulin-producing cells. Diabetes can be caused by little or no insulin production, or by the body´s inability to process the insulin it produces. This imbalance in insulin use causes blood glucose (sugar) levels to rise, which can be very harmful to the body.

2. How many types of diabetes are there?

There are several types of diabetes, but the most common are Type 1 and Type 2. Each requires different treatment since the cause of the disease is not the same.

3. What is Type 1 Diabetes Mellitus?

Type 1 diabetes generally occurs in people under 30 and is caused by the islets´ incapacity to produce enough insulin. The body´s own defense cells (antibodies) promote progressive islet destruction. Type 1 patients depend on daily insulin injections, thus being called insulin dependent. They make up 10% of diabetes patients.

4. And Type 2 Diabetes Mellitus?

Type 2 diabetes generally occurs in people over 40. It has a strong genetic component and is frequently associated with obesity and lack of physical activity. In this type, insulin production may be normal or even increased, but the body is not able to use it. This is called insulin resistance.

In Type 2 diabetes the high blood sugar levels can be controlled with a proper diet and/or oral medication. It accounts for 90% of diabetes cases.

5. What blood sugar alterations occur in diabetic patients?

Diabetics may present two extremes regarding glycemia. One is hypoglycemia, which occurs when blood sugar levels are low (very common during a long interval between meals or after strenuous exercise). The other is hyperglycemia which is exactly the opposite: blood sugar levels are too high. This can happen, for instance, as a result of diet exaggeration (overeating). In both cases it is necessary to measure blood sugar levels and contact the physician in charge.

6. What are the consequences of diabetes?

As a consequence of diabetes small blood vessels are damaged as well as organs such as the eyes, skin, nerves, muscles, intestines and the heart. The kidneys are no loger capable of filtering blood properly when its blood vessels are damaged. In this case, elimination of excess water and salt is hampered and toxic substances accumulate in the blood. Vessels in the retina (the area responsible for eyesight) may also be damaged by diabetes, leading to blindness. Vessels in the heart and brain are also affected, leading to heart attacks and strokes. When the nerves are damaged by diabetes (neuropathy), there is difficulty in emptying the bladder, which may lead to urinary infections and numbness of legs and feet, facilitating the appearance of wounds which, if infected, may lead at a more advanced stage to limb amputation.

7. How does the body control blood sugar levels?

As the body´s natural blood sugar control method (through insulin) does not work properly, the patient will have to control these levels artificially, through medication or introduction of insulin (injections), depending on each case.

8. What are pancreas islets or Islets of Langerhans?

The insulin-producing cells are also known as Islets of Langerhans. An islet is a cluster of cells in the shape of a microscopic “sphere”. They are distributed throughout the pancreas, an organ located behind the stomach. The islets were first studied and described by Paul Langerhans in1869, hence the name Islets of Langerhans.

An adult pancreas contains 700,000 to 1.2 million islets, representing 2 to 3% of the organ´s total mass.

9. How is ISLET ISOLATION carried out for the transplant?

The islets are extracted from the pancreas, coming from the same heart, lung, liver, kidney and cornea donors. Donors and their families must decide previously that in the event of death, the patient (donor) organs will be donated. Isolation starts with the preparation of the donated pancreas. An enzyme (digestive) solution is injected in the organ to begin pancreatic digestion. The pancreas with the enzyme solution is then placed in a stirring chamber to break the tissue down into smaller pieces. The pancreatic tissue is filtered, resulting in a non-purified tissue, where the islets are located. This tissue in washed several times so as to obtain only Is lets of Langerhans as a final result. The purified tissue will be used in the transplant. This procedure takes from 6 to 10 hours.

10. How is the islet transplant performed?

Once in the hospital, the patient will sign a consent form authorizing the transplant. Shortly after that, pre-transplant medication will be administered, lab exams and chest X-rays will be performed. A minor surgery is performed by a radiologist, with local anesthesia. A catheter (thin tube) is inserted into the right side of the abdomen, where the liver is located. Depending on the case, this procedure may last from 30 minutes to several hours. The cells are injected in the liver via the catheter, which is removed soon after the transplant.

The patient returns to his or her room to lie down for 4 hours, during which time vital signs and glucose levels will be monitored. Lab and ultra-sound exams are performed to make sure there is no internal bleeding and that blood is flowing normally through the gateway vein ( the vein through which the cells were injected). If these exams show satisfactory results, the patient will be discharged. Hospital stay ranges from 12 hours to 4 days.

11. Can a family member donate islets?

No. The whole pancreas must be processed in order to obtain enough islets to revert diabetes, and the pancreas is a vital organ.

12. Who qualifies for the transplant?

Type 1 diabetes patients aged 18 to 65 who have not shown adequate response to insulin therapy and show one or more of the following complications:

• Unawareness of hypoglycemia (low blood sugar);
• Metabolic instability (extreme variations of blood sugar levels), despite being on a strict diet and on insulin therapy;
• Patients who present progressive diabetes complications such as loss of eyesight, severe damage to kidneys and nerves (loss of sensitivity) as well as vascular problems (peripheral circulation).

13. Who does not qualify for the transplant?

Patients who present:

• Severe heart conditions;
• Mental illness that leads to the disregarding of one´s own health;
• Hystory of alcoholism or drug abuse;
• Active infection or malign disease (cancer);
• Bodyweight 25% over the ideal weight (obesity);
• Type 2 diabetes mellitus;
• Chronic kidney failure;
• Possibility of pregnancy (medication may affect the fetus);
• Patients who smoke.

14. Why can Type 2 diabetes patients NOT undergo the tranplant?

The objective of this transplant is to return insulin-pruducing cells (islets) to the patient´s body. In Type 1 diabetes, these islets were wrongfully detroyed by the body´s own immune cells. That is why these patients are targeted for this treatment. Type 2 diabetes patients do possess functioning cells, that is, they produce insulin. The problem is that their muscle and fat cells are unable to use the insulin which is released (what is called “insulin resistance”). Therefore, this type of treatment is not indicated for these patients.

15. What is the success rate of islet transplants?

According to current literature, the results of the appliance of the Edmonton Protocol (Canada-2001) are: 85% of transplantees reach insulin independence within the first year and 70% in the second year after the procedure (www.med.alberta.ca/islet). However, as it is a relatively new treatment, there are still no long-term result reports.

16. How is life after a transplant?

After the transplant, the patient will be responsible for taking care of the transplanted cells. Such care will be vital for the cells to work properly and, consequently, for the success of the treatment. The patient must use imunossupressing medication (to avoid rejection) for as long as these cells remain functional. This medication may have to be taken during the patient´s entire lif e. Without the medication and proper care, the patient will be contributing to the failure of the treatment. Patients must carefully monitor glucose levels and, initially, continue insulin use, because the transplanted cells need some adaptation time (“catch on” time) to their new site (the liver). The need for insulin use will vary on an individual basis and adjustments will be made by the professionals in charge. It is important to point out that the patient may have to undergo more than one transplant until a sufficent number of functional cells is reached which will allow insulin independence.

The success of the transplant is like a harvest: not every seed that is sown will grow to become a plant. However, if you prepare the soil well and water the seeds, you will increase the chances of a good harvest.

17. What is the cost of the transplant?

As it is a relatively new procedure in Brazil , the total costs are not yet defined. The entire team, along with the Brazilian Ministry of Health and other partners, will study the best way of promoting its access to the population. In Edmonton , Canada , the pancreas processing for islet isolation alone costs US$ 10,000 (ten thousand dollars) on average. Moreover, post-transplant monthly medication costs are estimated at US$ 500 (five hundred dollars). There will be no costs to the first 12 transplantees in Brazil.

18. If I already have a transplanted organ, can I be a candidate for islet transplant?

The current criteria do not offer islet transplant to patients with a transplant history . However, with the advancement of medical techniques it is likely that within a few years this hurdle will be overcome and patients with former tranplants will qualify for islet transplant.

19. Can there be rejection?

As in all transplants, the patient´s body, through its immune system (defense system), will identify transplanted cells as strangers and will activate this system to defend itself from “intruding” cells, thus rejecting these “foreign bodies”. To minimize the risk of rejection, immunosupressing drugs are administered.

20. What are the risks involved?

Among others, these are the main risks:

• Bleeding at the liver punction, regardless of the care taken during previous procedures;
• Portal vein thrombosis, although few cases have been reported;
• Infections triggered by the use of immunosupressing medication

21. Is this treatment a cure?

No. Islet tranplant is a form of long-term treatment for Type 1 diabetes patients. The transplanted cells will carry out their insulin-producing role as long as they remain functional and in sufficient numbers. There is the added risk of rejection. It is a research program still in progress, whose long term results are not yet known. Even though a sufficient number of cells will produce insulin and the patient will no longer need to take insulin, we do not use the term “cure” because there will always be the need for anti-rejection medication.

22. Why are patients under 18 years of age not permitted to receive this transplant?

The bodily systems of children and adolescents have not reached full development, and they therefore have a certain degree of fragility . In children particularly, there is an increased risk of portal vein thrombosis (obstruction of the vein in which the islets are injected). Due to this and other health concerns (such as prolonged use of immunosupressors) the minimum age of 18 has been set for transplant eligibility.

23. Is this treatment (islet transplant) considered an experimental procedure?

Yes. In the United States , the FDA (Food and Drug Administration) considers it an experimental procedure. Therefore, transplant centers need previous govermnmental authorization to do the procedure . Very careful monitoring of the cell isolation process is vital to make sure that the cells will not carry the risk of bacterial or viral infections to the patients. Our laboratory will also obtain the proper authorization from the Brazilian authorities and will perform several isolation procedures before the first trasnplant is carried out in humans. We need to make sure that the isolated cells are free of contamination caused by bacteria or other microorganisms. However, in Canada the islet transplant is already regarded as a legitimate form of therapy for diabetic patients.

CRITERIA FOR INCLUSION

• Type 1 Diabetes Mellitus for over 5 years
• Age between 18 and 65
• Unstable metabolic control
• Asymptomatic Hypoglycemia
• Poor blood glucose control (HbA1c) > 8,0%
• Progressive diabetes complications

CRITERIA FOR EXCLUSION

• Basal C Peptide >0.3
• C Peptide >0.3 after stimulation
• HbA1c>12%
• Insulin need >0,7UI/Kg/dia
• Body Mass Index >26 kg/m 2
• Hemoglobin <12.0mg/dl
• Creatinine clearance <60ml/min
• Macroalbuminuria (>300mg/24hrs)
• Alteration of liver function
• Alteration of thyroid function
• Dyslipidemia
• Alteration of coagulogram
• Biochemical alterations
• HIV, HBsAg/HCV/HTLVI positive sorology
• PSA > 4
• PRA >20%
• Previous transplant
• Cancer history
• Chest X-ray showing evidence of infection
• Active infection
• Abnormal abdominal echography
• Abnormal mamography
• Gynecological exam showing evidence of active infection
• Unstable cardiovascular status
• Untreated proliferative retinopathy
• Abnormal odontological exam
• Positive PPD
• No medical care for the previous 6 months or longer
• Pregnancy or breastfeeding
• Smoking, alcoholism and illegal drug use
• Any condition which might deem the islet transplant unsafe