2024-01-27 18:16:35
Despite advances in therapeutic strategies to treat type 1 diabetes (T1D), exogenous insulin administration remains the daily routine of the vast majority of patients. Indeed, if it is now possible to restore the production of the hormone through transplantation, its widespread clinical application involves many challenges. Recent pharmacological approaches aimed at regenerating pancreatic β cells could be a game-changer. We spoke to an expert in hopes of finding out if this strategy might actually be available in the relatively near future.
Type 1 diabetes (T1D), or insulin-dependent diabetes, is characterized by the autoimmune and irreversible destruction of pancreatic beta cells, responsible for the synthesis, release and storage of insulin. These cells represent approximately 50 to 70% of the total islet cell mass of the human pancreas. While symptoms generally do not appear until 80% of beta cells are lost, dysregulation of blood sugar leads to multiple long-term complications, such as diabetic nephropathy, neuropathy, retinopathy, cataracts and cardiovascular disease. .
It is estimated that approximately 8.42 million people
suffered from T1D worldwide in 2021, with almost 510,000 new cases each year. 60% of cases are concentrated in the 10 countries with the highest prevalence in the world, including the United States, India, Brazil, China, Germany, the United Kingdom, Russia, Canada, Saudi Arabia and Spain. Recent modeling suggests that the annual prevalence of the disease could reach between 13.5 and 17.4 million by 2040 and that the greatest increase would be seen in low- and middle-income countries.
Overpriced insulin doses
The loss of beta cells means that patients suffering from T1D must monitor their blood sugar levels daily and compensate for their insulin deficiency in order to maintain levels close to normal. To do this, first-line treatments generally consist of daily insulin injections. Insulinotropic medications (stimulating insulin production) may also be prescribed in certain cases.
« People with type 1 diabetes rely on injected or pumped insulin for the rest of their lives to regulate their blood sugar levels », confirms in an e-mail to
Trust My Science Assam El-Osta, distinguished epigeneticist from the Baker Heart and Diabetes Institute and Monash University (in Australia). However, “even though current therapeutic approaches to type 1 diabetes save lives, it is currently estimated that fewer than one in five patients achieve meaningful blood sugar control through insulin injection,” he said. added in response to our questions.
Additionally, insulin doses are not only overpriced, but also unavailable in many parts of the world due to lack of supply. In 2020, the average price per dose in the United States (all types of insulin combined) was
98,70 dollarscompared to 12 dollars and 9.08 dollars in Canada and France respectively.
Chart comparing the average price of insulin in 2018 in several countries around the world. © Mulcahy AW, et al. RAND Corporation, 2020
On the other hand, greater metabolic control (through intensive insulin therapy for example) makes it possible to prevent or reduce the incidence of secondary complications linked to the disease. However, it still presents high risks of hypoglycemia and weight gain. Furthermore, although these techniques stabilize blood sugar levels, they cannot reverse or slow down the destruction of beta cells.
Islet transplantation faces many limitations
The most advanced current treatments aimed at restoring beta cell function consist of either whole pancreas transplantation or pancreatic islet (or islet of Langerhans) transplantation—a relatively less invasive procedure than the former. Unlike previous strategies, aimed solely at maintaining blood sugar levels close to normal, transplantation aims to restore normoglycemia by reestablishing the endogenous and regulated secretion of insulin and other hormones produced by the islets of Langerhans.
A 90% success rate of one-year functionality of islet allografts has been reported by various health centers over the past two decades. However, this alternative faces significant challenges to its widespread application. In fact, the pancreatic islet transplantation
consists of isolating grafts from the pancreas of a deceased donor, then injecting them via the portal vein under immunosuppression. Although in some cases islets have been collected from living donors (by partial pancreectomy), the postoperative complication rate is so high that this method is chosen very rarely.
The main advances in treatment for T1D, from the discovery of insulin to the latest regenerative therapies. © Marie-Christine Vantyghem et al.
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On the other hand, “although their clinical utility has been proven, these therapies face the harsh reality of donor shortages as well as the associated side effects of immunosuppressive drugs,” El-Osta explains to Trust My Science. Indeed, insulin independence requires up to 2 to 3 infusions, with a goal of 9000 islets per kilogram of body weight of the recipient. Approximately 3 pancreases are required to generate sufficient islets for transplantation into a single recipient. On the other hand, the costs of the intervention (which is only carried out by a few specialized establishments in the world), from the isolation of the islets to the transplantation and postoperative follow-ups, are considerable.
In order to overcome these challenges, different potential sources aimed at producing beta cells in large quantities are being investigated. The cells are, for example, produced from the differentiation of human or embryonic pluripotent stem cells. Different molecules, including soluble growth and transcription factors, have been used for this purpose. However, the poor reproducibility of differentiation protocols constitutes a major challenge. Indeed, attempts at regeneration have until now been relatively hazardous.
Regenerative drugs already approved by the FDA
In view of the difficulties associated with previous strategies, there is an urgent need to identify new treatments that stimulate growth and restore beta cell function. In this vision, pharmacological approaches have recently been explored for reactivation or regeneration on site of these cells.
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