Indications for clinical islet transplantation today and in the forseeable future--the diabetologist's point of view.

ABSTRACT

The treatment of patients with type 1 diabetes mellitus has to focus on short-term and long-term risks of the disease which means to avoid hyperglycemic or hypoglycemic coma as well as late complications. As we know from the DCCT study metabolic control substantially lowers the risk for retinopathy, nephropathy and neuropathy. We also know, that keeping the blood glucose in a nearly normal range inevitably is connected with a marked increase of severe hypoglycemia, an event which occurs more frequently when normoglycemia has been reached and the further slow decline of blood glucose is not recognized by the patient (autonomous neuropathy, hypoglycemia unawareness of other origin, long duration of diabetes etc.). Furthermore, counterregulatory hormones as glucagon and epinephrine may be lacking due to diminished or even lost alpha cells within the islets and as recently observed due to fibrosis of the adrenal medulla in long-term diabetes. The consequences of severe hypoglycemia are manifold in the actual situation of unconsciousness the risk of heavy injuries and as long-term consequences irreversible brain damage may occur. Finally, the effort of the patient to reach normoglycemia includes the burden of an intensive blood glucose self-control day by day. This broad scenario of all the achievements and of all the problems connected with an intensified insulin treatment has to be regarded when the indication for an islet transplant will be discussed. From our point of view as clinicians it seems adequate not to give definite recommendations but to express our considerations for islet transplantation in patients with type 1 diabetes mellitus with the following list (table 1). It must be clearly stated, that at present transplantation of isolated islets by no means can serve as a treatment for a larger number of patients and this may hold through also for the foreseeable future. In this context, also the many contraindications should be summarized (table 2). Consequently we have to deal with several questions and problems which can be subdivided into those regarding the possible benefit for the patients from an islet graft (full success = insulin independence, partial success = lower exogenous insulin requirement due to additional endogenous insulin, measured by C-peptide levels, more stable glucose metabolism) and those regarding possible side effects (primary risk of implantation, threat for rejection of the primarily transplanted kidney). Furthermore, one may ask for risks when islets are transplanted alone (ITA). We therefore will address the following areas 1. Simultaneous islet and kidney transplants 2. Islet transplants after kidney transplantation alone (IAK) 3. Islet transplantation after pancreas transplantation failure (P-failure) 4. Defect hypoglycemia counterregulation--life threatening hypoglycemia unawareness as indication for islet transplantation? 5. Autonomous cardiac neuropathy as indication for islet transplantation? 6. Significant clinical problems with exogenous insulin therapy as indication for islet transplantation?