The criteria for selecting candidates for islet transplantation continue to evolve and the risk-benefit calculation for each patient remains somewhat subjective. In many respects, the current selection criteria are similar to those for whole pancreas transplantation (57). Since the procedural risks of islet transplantation are lower than that of pancreas transplantation, one could argue that the selection criteria could be less restrictive. Although, the post-transplant decline in insulin independence has made it more important to select candidates who will clearly benefit from a stabilization of glucose control, even if insulin independence is never achieved. Currently, three basic criteria are used for the selection of islet transplant candidates. These are: 1) frequent episodes of severe, undetected hypoglycemia, 2) severe glycemic lability, or 3) progressive diabetic complications, despite optimization of insulin injection therapy. The percentage of recipients meeting at least one of these criteria is listed in Table 2.
Table 2. Selection criteria for islet transplant candidates at the University of Alberta
|
Selection Criteria |
% Transplanted |
|---|---|
|
Frequent Undetected Hypoglycemia |
94% |
|
Glycemic Lability |
57% |
|
Progressive Diabetic Complications |
4% |
Of the three principle criteria, the first two are the most immediately correctable with islet transplantation (Figure 6). Glycemic lability and frequent severe hypoglycemia are generally eliminated after transplantation, even in those patients who do not achieve insulin independence. However, there appears to be a re-emergence of hypoglycemia in recipients who lose graft function (Figure 7) (58). The impact of islet transplantation on secondary diabetic complications remains unclear. Early reports from small, non-randomized series of patients suggest that there may be stabilization of diabetic retinopathy and neuropathy (59) and improvement in cardiovascular function in islet-after-kidney transplant recipients (60). However, the full impact of islet transplantation, especially in patients without kidney transplants, will require much longer follow-up to be clearly understood. Therefore, patient selection currently focuses on individuals with very labile glucose and/or frequent undetected hypoglycemia. In general, transplant candidates who meet only the "progressive complications" criterion without meeting at least one of the other two are not accepted for transplantation.
Figure 7. The HYPO score pre and post transplant in those who remain C-peptide positive. Pre-transplant n = 31, at one year n = 40, at two years n = 29, at three years n = 15, at four years n = 7and at 5 years n = 5. Copyright 2005 American Diabetes Association from Diabetes, Vol. 54, 2005; 2060-2069. Reprinted with permission from The American Diabetes Association.
To assess glycemic lability, the mean amplitude of glycemic excursion (MAGE) has been used, which compares the standard deviation of capillary glucose values measured seven times per day over a two-day period (61; 62). A MAGE score greater than ten is thought to represent poor glycemic control. The risk of hypoglycemia is also difficult to assess, since there is no objective standard by which it can be measured. Currently, clinical judgment, using the patient's blood glucose records and history of hypoglycemic events remain the best tools by which these risks can be judged. Recently a scoring system has been developed by which glycemic lability and hypoglycemia may be more objectively compared (63). Another method for assessing glycemic lability may be the continuous glucose monitor (64). It is anticipated that such methods will aid in the appropriate selection of islet transplant candidates.