Counterpoint: Clinical Islet Transplantation: Not Ready for Prime Time

Abstract

β-Cell replacement therapy's great promise is that it can safely and effectively restore insulin-independent euglycemia to individuals with diabetes. Although difficult and expensive, modern insulin-based treatment for type 1 diabetes has lead to remarkable improvements in disease prognosis (1–3). Based on recent population-based epidemiological studies, we have estimated that an individual diagnosed with type 1 diabetes today faces an excess mortality over the next 20 years of ∼2% or ∼0.1% per year (4). Even individuals with long-standing type 1 diabetes sufficiently problematic to be listed for a pancreas transplant have an annual mortality <2.0% per year (5). The perceived weaknesses associated with intensive insulin therapy are its cost estimated in 1996 to be 116,000 USD over a lifetime (6) and its inconvenience requiring meticulous attention to diet, exercise, frequent daily blood glucose measurements, and multiple daily injections. In addition, insulin therapy carries with it an increased risk of serious hypoglycemia (1). We attempt to address whether current β-cell replacement therapies overcome the shortcomings associated with medical management. Certainly, β-cell replacement therapy should not increase the subjects' risk above that associated with standard clinical care. For patients with type 1 diabetes and end-stage kidney disease, simultaneous pancreas-kidney (SPK) transplantation has appropriately achieved standard of care status. SPK recipients can reasonably expect improved and sustained insulin-independent metabolic control, and the surgery demonstrably improves survival rates compared with those medically treated (5). However, the options are much less clear for subjects with long-standing diabetes and preserved kidney function defined as a serum creatinine <2.0 mg/dl. (And with modern therapies, an ever-decreasing minority will develop renal failure.) For such patients, pancreas transplant alone (PTA) or pancreas-after-kidney (PAK) transplantation, despite reasonable insulin-independence rates, does not improve survival and may even increase mortality (5). The underlying cause of the apparent excess mortality post–pancreas transplantation …