Prospects for the prevention and reversal of type 1 diabetes mellitus.

Type 1 (insulin-dependent) diabetes mellitus results from selective immune-mediated destruction of pancreatic islet beta cells. Strategies to prevent or reverse the development of diabetes can be divided into three groups, depending on whether they focus on beta-cell protection, regeneration or replacement. Prevention of immune beta-cell destruction involves either halting the immune attack directed against beta cells or making beta cells better able to withstand immune attack, for example, by making them resistant to free radical damage. The recent identification of beta-cell growth factors and development of stem cell technologies provides an alternative route to the reversal of diabetes, namely beta-cell regeneration. Interestingly, stem cell-derived islets appear to be less sensitive to recurrent immune destruction that is normally seen in response to islet transplantation. The last alternative is beta-cell replacement or substitution. This covers a wide range of interventions including human whole pancreas transplantation, xenotransplantation, genetically modified beta cells, mechanical insulin sensing and delivery devices, and the artificial pancreas. This review describes recent advances in each of these research areas and aims to provide clinicians with an idea of where and when an effective strategy to prevent or reverse diabetes development will become available.