IN CONSULTANCY WITH
PROF. Emanuele BOSI
CHIEF PHYSICIAN OF INTERNAL MEDICINE AND DIABETOLOGY
IRCCS OSPEDALE SAN RAFFAELE (MILAN)
PROF. Lorenzo PIEMONTI
DIRECTOR OF THE DIABETES RESEARCH INSTITUTE (DRI)
IRCCS OSPEDALE SAN RAFFAELE (MILAN)
On 11 January 1922 in Toronto, Canada, Leonard Thompson became the first person in the world to receive an insulin injection. More precisely, the fourteen-year-old boy from Ontario suffering from type 1 diabetes did not receive insulin, as we know it today, but a progenitor of the hormone that regulates blood glucose levels. It was a partly purified suspension, obtained from animal pancreas: a groundbreaking discovery for all those living with diabetes, achieved by scientists Nicolae Paulescu, John James Rickard Macleod, Frederick Grant Banting and Charles Best. The suspension's impurity meant that the first attempt had few clinical benefits and many side effects, including an abscess at the site of the first injection.
It was only thanks to biochemist James Collip Bertrand, who worked tirelessly for 12 days to obtain a second, purer suspension, that on 23 January a second injection was carried out, and for the first time a clinical outcome with minimal side effects was achieved. It was a breakthrough: the form of diabetes now known as type 1, whose diagnosis up to that point was effectively a death sentence, had become clinically treatable.
From that moment, an unstoppable race began that led to key discoveries that would change the history of the disease. Over the last twenty years, progress in the treatment of type 1 diabetes has undergone a notable acceleration, due in part to a significant increase in the disease's occurrence: a recent study by Queen's University Belfast found an annual increase of 3.4% in Europe alone in new cases of type 1 diabetes in childhood and adolescence, but doctors and scientists are as yet unable to provide an explanation for the causes and triggering factors behind the disease.
Type 1 diabetes
Is a chronic autoimmune disease primarily diagnosed in children and teenagers, although there may also be late diagnoses in adults. The problem lies with the immune system attacking and destroying beta cells, the cells inside the pancreas that produce insulin, the hormone that regulates the metabolism of glucose in the blood. Due to this lack, insulin must therefore be supplied externally through multiple daily injections (four per day on average), to be continued for life.
Is extremely complex to manage and deal with, starting with choosing the injection site (abdomen, buttock, thigh and the deltoid region of the arm), which must be rotated to a different area every time to prevent local reactions such as lipodystrophy (alteration of the subcutaneous fat that interferes with the correct absorption of the insulin and its optimal transfer into circulation). Furthermore – and this is the most challenging aspect – the person must autonomously monitor and regulate the dosage and frequency of their insulin administration based on their glycaemic pattern, the concentration of sugar in the blood.
Blood glucose levels must be measured before and after meals, at night, and in the event of signs of feeling unwell, which could indicate a state of hypo- or hyperglicemia.
Over the last few decades, technological developments have brought improvements in the measuring of blood glucose and in insulin management. Firstly, in the development of glucose sensors, i.e. devices that are small in size – and therefore relatively comfortable to wear – capable of continuously reading glycaemic values through a microneedle that penetrates the skin, and of memorising the daily-recorded data which can then be viewed on a smartphone. Secondly, rather than being administered through multiple daily injections, the insulin itself can be dispensed continuously through a micropump, a small wearable device which, in its most technologically advanced form, can adjust the administration of insulin based on information supplied in real time by the glucose sensor.
“The new technologies applied to diabetes are perhaps the most significant advance that we have seen in the field of the disease's treatment”, explains Professor Emanuele Bosi, Chief Physician of Internal Medicine and Diabetology at the IRCCS Ospedale San Raffaele, “especially in terms of the impact they have on patient quality of life. They free the patient from having to constantly think about blood glucose monitoring, and the synergy between the glucose sensors and the insulin pump is moving us towards the goal of an artificial pancreas, that is, a set of instruments that are capable of standing in for the endocrine pancreatic function, the lack of which is behind type 1 diabetes.
However, there may be people who, even with the use of the most advanced technology, cannot keep their blood glucose under control for a variety of reasons, such as, for instance, the impaired subcutaneous absorption of insulin. In such cases, thankfully rare, one option is to administer the insulin in alternative ways to the subcutaneous injection, that is, intraperitoneal infusion”, continues Professor Bosi.
Since 2019, in some centres, including the IRCCS Ospedale San Raffaele, it has been possible to be fitted with the Diaport system, consisting of an intraperitoneal catheter connected to an external pump worn by the patient. Once absorbed, the insulin heads from the abdomen to the liver as the main target organ, exactly as would happen in physiology following the secretion of insulin from the pancreas.
While seeking more effective solutions for controlling diabetes, is also aiming to find a way to restore pancreatic function. “Total recovery from diabetes consists in the possibility of reconstructing the missing supply of insulin-producing pancreatic beta cells; today, pancreatic islet transplantation makes it possible to extract beta cells from the pancreas of an organ donor, isolate them from the rest of the organ, and infuse them into the recipient's liver via injection into the portal vein”, explains Professor Lorenzo Piemonti, director of the Diabetes Research Institute at the IRCCS Ospedale San Raffaele. Today this intervention is no longer considered an experimental treatment, but a clinical procedure.
Not all patients with type 1 diabetes are suitable candidates for this treatment
Given that it is a transplant, by definition there is a risk of rejection; to prevent this, it is necessary to take immunosuppressants on a lifelong basis. In the long term, however, these can produce side effects. Researchers are therefore looking for a way to refine the technique and improve the results of the treatment. This kind of problem could be resolved through the development of a therapy using stem cells.
In light of this, the launch of the Beta Cell Therapy Consortium was announced last January: a European clinical trial of pluripotent stem cells in patients affected by type 1 diabetes. This is a phase 1 clinical trial whose ultimate goal is to evaluate the capacity of the stem cells, still immature by definition, to differentiate themselves in beta cells for the production of insulin. More good news for diabetic patients comes from the United States, and concerns a study published in Nature Cell Biology: a team of researchers from the University of California San Diego, starting from human stem cells, has succeeded in replicating in the laboratory mature insulin-producing cells that imitate the action of pancreatic beta cells. This breakthrough opens up new treatment scenarios for type 1 diabetes. “This study confirms that we are moving ever closer to our goal, that of a definitive treatment for diabetes through the creation of pancreatic beta cells in the laboratory”, concludes Professor Piemonti.
By: Lara Anna Stoinich
Translation: TDR Translation Company
Editing: Victor Cojocaru