Felix dies natalis, insulin… ceterum autem censeo “beta is better”

Benefits and Hurdles of Pancreatic β-Cell Replacement

“… 8 , 9 Islets of Langerhans can be considered as organs that are arranged in a highly organized structure, with functional interactions, and are part of a complex exocrine/endocrine network that regulates glucose levels and more generally nutrient metabolism. 3 , 27-30 Restoring the whole islet’s physiological function, may represent a cure, and permit to maintain the normal glucose control, while insulin therapy, even with the most advanced technologies and devices, cannot reproduce this level of complexity.…”

“… 7 The main indication is represented by severe hypoglycemia unawareness, in specific patient populations with unstable diabetes; kidney transplantation can be combined if the end-stage renal disease is concomitant. 3 , 7 , 11 , 13 , 31 Importantly, a clear outcome definition of function and failure of β-cell replacement therapies was recently defined, which considers also continuous glucose monitoring metrics. 32 Pancreas transplantation represents a long-term treatment that restores normal glucose homeostasis and may prevent, stabilize, or even reverse progressive diabetic complications 12 ; it requires lifelong immunosuppression and is a major surgical procedure that entails non-negligible risks for the recipient, thus not suitable for all patients.…”

“… 32 Pancreas transplantation represents a long-term treatment that restores normal glucose homeostasis and may prevent, stabilize, or even reverse progressive diabetic complications 12 ; it requires lifelong immunosuppression and is a major surgical procedure that entails non-negligible risks for the recipient, thus not suitable for all patients. 3 , 9 , 12 Pancreas transplantation is more frequently performed simultaneously with a kidney transplant, or after kidney transplant, with a positive impact on diabetes complications and life expectancy. 33 , 34 Recent data reported 10-year outcomes following pancreas transplantation alone in subjects with T1D and BMI <30 kg/m 2 , showing 7.6% overall mortality and good or excellent pancreas allograft function (death censored) in 60% of participants.…”

“…Type 1 diabetes (T1D) is a chronic autoimmune disease that results over time in an immune-mediated loss of functional pancreatic β-cell mass, leading to symptomatic diabetes and lifelong insulin dependence. 1 , 2 In 2021, we celebrated the centenary of insulin discovery, the first therapeutic protein that was produced with recombinant DNA technology in 1982 3 ; insulin therapy determined a dramatic improvement in life expectancy, 3 , 4 but people with T1D, even if inadequate glucose control, still show an increased mortality risk compared to non-diabetic subjects. 5 Year by year new technological devices are becoming available and allow improvements in metabolic control and quality of life 6 , 7 ; however, insulin remains a therapy and not a cure for the disease.…”

Treating iPSC-Derived β Cells with an Anti-CD30 Antibody–Drug Conjugate Eliminates the Risk of Teratoma Development upon Transplantation

“…Type 1 diabetes (T1D) is a disease resulting from the autoimmune-mediated destruction of insulin producing β cells of the pancreas. Despite significant advances in T1D management, exogenous insulin administration does not guarantee an optimal glycemic control and protection from long-term complications [ 1 ]. Allogeneic islet transplantation allows the reestablishment of glycemic control with the possibility of insulin independence, but this approach is severely limited by the scarcity of organ donors [ 2 ].…”