Endocrine Abstracts

The DCCT conclusively confirmed that long-term microvascular complications of Type 1 diabetes can be prevented by restoration of near-normal glucose levels. Despite ongoing refinements in management including structured re-education, optimized insulin analogue regimens, continuous subcutaneous insulin infusion and even steps towards the bioartificial pancreas, exogenous insulin replacement is inextricably linked to risk of severe hypoglycaemia.

Transplantation of whole pancreas from deceased donors has confirmed that successful ß-cell replacement restores physiological glucose sensing and insulin secretion. This enables blood glucose lowering in tandem with absolute prevention of hypoglycaemia. Pancreas transplantation has largely been confined to those with end-stage renal failure given the need for a major operation with associated morbidity and mortality.

Successful transplantation of insulin-secreting islets following minimally invasive portal vein cannulation was realized in Edmonton, Canada in 2000. Although 90% had recommenced ‘top-up’ insulin injections at 5 years, graft function was maintained in 80% with mean HbA1c 6.5% and no major hypoglycaemia. Success has been replicated world-wide in insulin-sensitive individuals with unresolved recurrent severe hypoglycaemia significantly impairing quality of life; and in those with sub-optimal glycaemic control who are already on life-long immunosuppression following a renal transplant. Islets have been successfully transported between centres, established in culture and manipulated in vitro prior to clinical transplantation. This has provided important proof-of-principle for future potential stem, human somatic and xenogeneic cell replacement approaches. These will be critical to overcome limitations imposed by restricted availability of suitable deceased donors sufficient for <1% of individuals with Type 1 diabetes.

Progress towards the next clinical milestone of reproducible long-term insulin independence following transplantation of islets from a single donor has already been made. Strategies include refinement of immunosuppression, optimization of engraftment and adjunctive treatments targeted at maintaining ß-cell mass.

Although still in its infancy, with further research required before widespread implementation can be contemplated, islet transplantation provides an evidence-based new therapeutic option for a carefully selected minority with complex type 1 diabetes unresponsive to conventional medical management.