Insulin Injections

Transplantation for Type I Diabetes

Introduction

In individuals with insulin- dependent diabetes, the insulin-producing cells (beta cells) are destroyed. In order to correct this they must either be injected with insulin or the beta cells should be replaced. Beta cells secrete insulin as needed to maintain normal blood sugar levels, turning on after a meal to assist in metabolism of the sugar absorbed, and turning off after a meal as soon as this is accomplished. A person who has diabetes is relegated to a life of trying to replicate the beta cells' automatic secretion of insulin with insulin injections, dietary restrictions, and blood glucose tests. Insulin injections require continual guesswork because dosing must vary with physical activity, emotions, medications, changes in mealtimes, sick days, and so forth. The consequences of guessing wrong often, over the long term, lead to secondary complications involving the eyes, (retinopathy), nerves (neuropathy), kidney's nephropathy, or blood vessels (cardiovascular disease). The consequences of guessing wrong in the short-term range from the mild mental and physical impairments associated with low blood sugar levels to life-threatening hypoglycemic unawareness. The only known treatments that can restore the natural and automatic secretion of insulin in response to blood glucose levels are pancreas and islet cell transplants.

The successful transplantation of beta cells, either as part of a whole pancreas or by an injection of isolated islets, is an ideal treatment for diabetes. Currently, however, only pancreas transplantation is consistently successful. As long as a transplanted pancreas functions, blood glucose levels are no different from those of people who do not have diabetes. But becoming insulin-free through transplantation bears a cost¾drugs to suppress the immune system are required to prevent the rejection of transplanted organs. For this reason most pancreas transplants are done for people with long-standing diabetes who already need a kidney transplant.

Kidney failure occurs in about 30 percent of individuals who have diabetes for 20 or more years By the time kidney failure develops, usually other diabetic complications are also present. Although a successful pancreas transplant is unlikely to improve advanced retinopathy, it can eliminate the need for insulin injections and greatly ease the day-to-day problems of health care for people who have severe vision loss. A successful pancreas transplant in conjunction with a kidney can prevent the recurrence of diabetic damage in those who have received a kidney. Pancreas transplantation, either in conjunction with or following a kidney transplant, is a routine treatment for diabetic kidney disease at most U.S. hospitals that perform transplant surgery. Indeed it is the best treatment available for those who are young enough and healthy enough to undergo a pancreas transplant when they develop kidney disease resulting from Type I diabetes.

Transplantation of pancreas

There are a number of different ways to approach pancreas transplantation. For people who need a kidney transplant and who are fortunate enough to have a living donor, a pancreas may be added later from a cadaver donor, or part of the living donor's pancreas may be transplanted in conjunction with the kidney. For those without a living donor, the pancreas and kidney are usually transplanted simultaneously from a single cadaver donor. By indicating that tight control of blood glucose levels reduces the incidence and severity of diabetic complications, the Diabetes Control and Complications Trial (DCCT) conducted by the National Institutes of Health provides a strong rationale for pancreas transplants alone to be done early in the course of diabetes. Ideally, a pancreas transplant alone is chosen before there is an irreversible need for a kidney. The intensive regimen of diabetes management recommended as a result of this study entails at least finger sticks at least four times a day to check blood glucose levels, as well as multiple daily injections of insulin. In spite of "intensive therapy" average blood sugar levels of the group practicing this regimen in the DCCT study, remained significantly above the normal non-diabetic levels. Additionally, the incidence of dangerous hypoglycemic episodes rose substantially. Some individuals have extreme swings in blood sugar in spite of careful monitoring while others develop secondary complications even when the average blood sugar is only moderately elevated. Clearly good control is not good enough for everyone. And so it remains that the only way to achieve consistently "perfect control" is with a successful pancreas transplant.

Why then doesn't everyone with Type I diabetes have a pancreas transplant? The answer lies in the uncertainty people have as to whether or not diabetic complications will develop, and over what time period, and uncertainty as to what side effects of immunosuppression drugs a person may experience if he or she undergoes a pancreas transplant. For this reason, very few pancreas transplants have been done soon after the onset of diabetes when the risk of secondary diabetic complications seems somewhat removed. Pancreas transplants, in the absence of the need for a kidney transplant, have largely been done for people who suffer with brittle diabetes and hypoglycemic unawareness. For these people a pancreas transplant can eliminate the risk of dangerous insulin reactions. The risks associated with transplantation are generally seen to be less than the life-threatening dangers of hypoglycemic unawareness.

There is no evidence that immunosuppressive drugs are associated with any more complications over a twenty-year period than the probability of complications from diabetes. Early pancreas transplantation can prevent secondary complications and, even when done late, has been shown to improve nerve damage caused by diabetes. It would be reasonable for a person with diabetes to choose to have a pancreas transplant with long-term immunosuppression over choosing a lifetime with diabetes.

Indications for Pancreas Transplantation

Pancreas Transplant in addition to a Kidney Transplant

People who have diabetes should have an annual kidney function test. The test is comprised of a urine analysis and a blood test. Early signs of kidney damage most often include elevated blood pressure and protein in the urine. Typically people who's diabetes progresses to kidney failure have had diabetes for 15-30 years, will have persistently high blood pressure, fatigue and an increase in the blood chemical called creatinine. The need for a pancreas and kidney transplant cannot be determined exclusively on the basis of blood chemistry levels as these vary substantially from person to person. Chronic fatigue, the need for blood pressure medications, recurrent swelling (edema) requiring diuretics and anemia indicate that a person with diabetes will progress to kidney failure. In an attempt to avoid dialysis, people who have diabetic kidney disease should be referred early in the progression of their disease to a kidney specialist at a transplant program. This referral should be made when the creatinine level first begins to rise. Acting early allows the nephrologist to work with the transplant surgeon to arrange for the patient to be added to the waiting list for a cadaver donor pancreas and kidney or, ideally, to screen family members to determine who may be a donor. Keep in mind that a family member, spouse or friend may be screened and evaluated to donate both a kidney and half of their pancreas.

Pancreas Transplant without a Kidney Transplant

People who choose to have a pancreas transplant alone typically do not have kidney failure, although some changes in the blood or urine chemistries may have been detected. People who had lived with diabetes for several years and have developed nerve damage with decreased sensation in hands or feet may also no longer experience the symptoms of a low blood sugar level. Blood sugar levels may drop precipitously without symptoms and can lead to unconsciousness. These unconscious reactions often require the assistance of another person and can be life threatening. Maintaining slightly higher blood sugar levels reduces the risk of severe hypoglycemic episodes but, at the same time, increases the chance of developing complications of the eyes, kidneys and heart. For this group, the risks associated with a pancreas transplant are less than the risks of continuing with labile diabetes.