Millions of people throughout the world are living with type 1 diabetes: an insulin-dependent form of diabetes characterised by insufficient levels of insulin being secreted by the pancreas.
The role of insulin is to promote the absorption of glucose (sugar) into the body’s cells. When glucose is not processed by the body's cells, it builds up in the blood and causes hyperglycaemia.
Insulin therapy remains the standard treatment for type 1 diabetes, with various methods of administration and associated technologies to improve patients' daily lives.
How many people are treated with insulin therapy?
About six million people are currently being treated with insulin therapy, with new types of treatment being researched or in development.
There are still many challenges to overcome:
- delaying the progression of type 1 diabetes;
- overcoming the immune mechanisms that cause the condition;
- preventing the onset of complications by developing better techniques for monitoring blood glucose levels;
- creating insulin delivery systems that mimic normal pancreas activity.
Treatment of type 1 diabetes with insulin therapy
In the early 1980s, the launch of the first insulin pen revolutionised the treatment of type 1 diabetes.
Compact, practical, discreet, and precise, it rapidly made a place for itself as an excellent alternative to syringes and vials.
The insulin pen consists of an insulin cartridge encased in a pen with a fine, single-use needle at the end. There are two types:
- rechargeable, in which an insulin cartridge is replaced;
- disposable, which is pre-filled and must be disposed of when empty.
The insulin pen is now the most widely-used treatment for diabetes worldwide. It is preferred for its ease of use and its precision in delivering the correct dose. Furthermore, subcutaneous insulin injections provide better glycaemic management than injections into the deeper layers of the dermis.
However, medical incidents (hypoglycaemia, bruising, or bleeding) resulting from incorrect use can occur in those who have chosen the insulin pen as a treatment method for type 1 diabetes. It is therefore important that patients who have adopted this type of insulin therapy be technically trained in its use and monitored regularly by health professionals.
The objective of insulin pumps is to provide regular doses of fast acting insulin. A continuous basal dosage is delivered throughout the day as needed, while an additional bolus dose may be given at mealtimes and in case of hyperglycaemia.
The insulin pump is a programmable device fitted with a detachable infusion system. It can be adjusted to suit the specifics and needs of each individual user. For example, it is possible to adjust the insulin delivery parameters according to the time of day or the user’s current situation (exercise, illness, etc.).
When was the first insulin pump invented?
The first attempt to create a portable insulin pump dates back to the early 1960s. Cumbersome and impractical, it was never marketed, it took another 30 years for the first versions of compact, practical, and reliable insulin pumps to be made available.
Today, the insulin pump is one of the most reliable and effective treatments for type 1 diabetes. It improves quality of life for people living with diabetes by providing optimal blood glucose control and limiting the risk of hypoglycaemia.
New treatment perspectives
As self-management of type 1 diabetes remains difficult and restrictive, demand for the development of closed-loop insulin therapy systems has grown considerably.
The first clinical studies showing the reliability of such devices were carried out in 2010. However, it was not until 2017 that the first device, incorrectly referred to as an artificial pancreas, was approved following non randomised clinical trials.
It is not a transplantable artificial organ, but a collection of technology combining a continuous glucose monitoring device (CGM), an insulin pump, and a control unit (sometimes within the insulin pump or via a smartphone).
How does the “artificial pancreas” work?
The control unit uses mathematical algorithms to automatically adjust the dose of insulin delivered subcutaneously by the pump depending on continuously-monitored blood glucose levels. Most artificial pancreas systems take a hybrid approach in which the patient manually triggers delivery of fast-acting bolus insulin before a meal.
The results obtained are very encouraging. Clinical studies have shown that use of an artificial pancreas increases the users time in range by 10%, reduces time spent in hypoglycaemia by half, and improves HbA1c (glycated haemoglobin) by 0.3 %.
Given its effectiveness, the artificial pancreas may well establish itself in the near future as the standard treatment for type 1 diabetes. The quality of life for people living with diabetes would be greatly improved, with enhanced control of their blood glucose levels not only making daily life more comfortable but also reducing anxiety, allowing better sleep, and giving greater flexibility in eating habits.
Pancreas and islets of Langerhans transplants, and stem cell therapy
There are currently two therapeutic strategies for replacing beta cells in the pancreas of people with type 1 diabetes:
- transplantation of Langerhans islets containing the insulin-producing beta-pancreatic cell;
- transplantation of a pancreas from a donor.
Both therapies have their limitations owing to the limited number of donors and the constraints associated with immunosuppressive treatment, as the patient is required to take medication to avoid graft rejection and this often causes a considerable number of side effects.
To overcome these obstacles, international research teams have been developing the technique of using the patient's own pluripotent stem cells as a base for generating unlimited insulin-producing cells.
Over the past decade, remarkable progress has been made in generating functional beta-pancreatic cells from human stem cells. However, often the patient’s immune system will attack the transplanted pancreatic cells.
To prevent rejection and increase the chances of successful treatment, laboratories are currently working on a number of solutions using encapsulation technology, immune modulation approaches, and gene editing techniques.
International teams of researchers have been working for several decades on the development of an insulin-based pill, with the goal of moving away from people with type 1 diabetes requiring daily insulin delivery, while also making it easier for them to maintain their treatment programs.
This treatment method is currently undergoing clinical trials. The challenge of oral insulin delivery is made all the more complicated as insulin is easily degraded by gastric acids present in the stomach and poorly absorbed through the intestine wall. It must therefore be encapsulated in a protective acid-resistant coating.
More recent experimental work has been carried out on capsules containing insulin suspended in an ionic liquid and coated with acid-resistant molecules. Following initial positive results, researchers must now carry out preclinical tests proving the capsules long-term non-toxicity.
Other researchers have developed a capsule capable of injecting insulin into the stomach lining using a microneedle to avoid perforation.
Today, other formats of insulin pill are also undergoing clinical trials. The aim is to determine the optimal dosage and the body's tolerance for these new oral treatments, which, if successful, could make life easier for people with type 1 diabetes.
Immunotherapy treatment: towards a diabetes vaccine
Type 1 diabetes is an autoimmune disease that causes the gradual destruction of insulin-producing beta cells.
The underlying concept behind the development of a diabetes vaccine is preventing the immune system from attacking the remaining pancreatic cells so that insulin production continues.
Over the past ten years, nearly 70 clinical studies have tested the effectiveness of a range of immunotherapy approaches capable of reducing the autoimmune reaction specific to type 1 diabetes.
One of the most promising avenues for the development of a diabetes vaccine is through the use of anti-CD3 monoclonal antibodies. This antibody reduces the loss of functional beta-pancreatic cells as late as seven years after the onset of type 1 diabetes.
A recent clinical study showed that the administration of anti-CD3 antibodies to family members of patients with type 1 diabetes, who are therefore at high risk of developing the condition themselves, slowed its progression by an average of two years.
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