Transplantation of islets of Langerhans in patients with insulin-requiringdiabetes mellitus undergoing orthotopic liver transplantation - the Miami experience

Most patients with cirrhosis of the liver have detectable insulin resistanc e. In 60-80% of patients with cirrhosis, impaired glucose tolerance can be uncovered; approximately 20% of these patients eventually develop overt dia betes. Theoretically, insulin resistance and glucose intolerance could be i mproved or reversed by orthotopic liver transplantation alone or in associa tion with a simultaneous transplant of pancreatic islet cells from the same donor. To investigate these possibilities we initiated a pilot study of si multaneous liver and pancreatic islet cell transplantation in seven patient s with diabetes and liver cirrhosis. Donor bone marrow cells were also infu sed to enhance the acceptance of the grafts. Seven patients who received on ly orthotopic liver transplantation and donor bone marrow cells were used a s historical controls. The preliminary results of this pilot trial suggest that islet cell transplantation in conjunction with orthotopic liver transp lantation improves glucose metabolism in patients with liver cirrhosis in a ssociation with reduced insulin requirements and HbA1c levels. These result s were evident in spite of pre- and post-transplant basal C-peptide levels that were unchanged. Further evaluation of the effects of orthotopic liver transplantation with or without islet cell transplantation will require a r andomized prospective trial including accurate metabolic evaluation with th e euglycemic insulin clamp technique.