Symposium: New horizons in the treatment of type 1 diabetes mellitus. Pancreas transplantation, islet trasplantation and pluripotent stem cells: which is the biological solution?

Abstract

This year marks the centenary of the discovery of insulin, carried out at the University of Toronto, Canada, by surgeon Frederick Banting and medical student Charles Best, with the collaboration of chemist James Collip, under the (disputed) direction of the physiologist Scotsman John Macleod. Since then, its use has helped save the lives of millions of people with diabetes.

Even today, in its different chemical formulations, exogenous insulin constitutes the main hormonal substitute to treat diabetes that requires or depends on insulin.

Although in the vast majority of patients this treatment works adequately, there is a proportion of them who do not have a good response. They suffer from episodes of hyperglycemia, which puts them at risk of secondary complications, and hypoglycemia, which can be the cause of death in the most serious situations.

Thus, the therapeutic goal for all patients with diabetes, but particularly for the lability group, is not only to provide them with the insulin they need, but also to do so in a way that achieves metabolic stability and can delay, slow or reverse the secondary complications of the disease.

Undoubtedly, the best way to restore the physiological metabolic control of glycemia is the provision of pancreatic beta cells. This can be accomplished by vascularized pancreas transplantation and pancreatic islet transplantation. Vascular transplantation is associated with very high rates of insulin independence and with patient and organ survival of about 94% at one year after transplantation. This impact is even more significant in patients with diabetes and end-stage renal failure, in whom it increases survival from around 50% without transplantation, to more than 87% at 5 years after transplantation.

On the other hand, pancreatic islet transplantation is a technically simpler procedure, but with lower insulin independence rates compared to vascularized transplantation (50% vs. 90%, respectively). However, it has a very marked benefit in terms of the absence of severe hypoglycemic episodes (90% at 5 years).

There are also other lines of translational research aimed at solving two fundamental problems: the shortage of organs for transplantation and the need for lifelong immunosuppression. In this sense, different strategies have been developed, such as immunomodulation, gene editing and transplantation of pluripotent stem cells capable of differentiating into insulin-producing cells.