What are the treatments of type 1 diabetes?

Millions of people worldwide are living with type 1 diabetes: an insulin-dependent form of diabetes characterised by insufficient levels of insulin being secreted by the pancreas [1,2,3].

The role of insulin is to promote the absorption of glucose (sugar) into body cells. When glucose cannot enter the body’s cells, it builds up in the blood and causes Hyperglycaemia (high blood glucose) [1,2,3].

Insulin therapy remains the standard treatment for type 1 diabetes, with diversified methods of administration and technological tools improving the daily lives of people with type 1 diabetes. [1,3,4].

New types of treatment are under investigation or in development. There are still many challenges to overcome: 

• delaying the progression of type 1 diabetes
• overcoming the immune response that causes the condition
• preventing the onset of complications by developing better techniques/methods for monitoring blood glucose levels
• creating insulin delivery systems that mimic normal insulin production activity [1,2,3,4,5,6,7,8,9,10,11]. 

Treatment of type 1 diabetes with insulin therapy

Insulin pens

In the early 1980s, the launch of the first insulin pen revolutionised the treatment of type 1 diabetes [3,8]. Compact, practical, discreet, and precise, it rapidly became an excellent alternative to syringes and vials [3,4,8].

The insulin pen consists of an insulin cartridge encased in a pen with a fine, single-use needle at the end [3,8]. 

There are two types:

• reusable, in which an insulin cartridge is replaced, 
• disposable, which is pre-filled and must be disposed of when empty [3,8].

The insulin pen is now the most widely-used treatment for diabetes worldwide [4,8]. It is preferred by physicians and people living with diabetes for its ease of use and precision in delivering the correct insulin dose. Correct insulin injection technique is essential to ensure correct insulin action. Discuss the injection technique with your healthcare provider. [1].

However, individuals who opt for insulin pens as a treatment method for type 1 diabetes may encounter complications such as Hypoglycaemia, bruising, or bleeding if they are not used correctly. Therefore, it is crucial for patients using this insulin delivery method to receive the proper technical training and regular monitoring by healthcare professionals [1,4].

Insulin pump

The objective of insulin pumps is to provide regular doses of fast and ultra-fast-acting insulin. A continuous basal dosage is delivered throughout the day as needed, while an additional dose may be given in case of Hyperglycaemia or when food is eaten (bolus dose) [3,8].  

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 user. For example, it is possible to adjust the insulin delivery parameters according to the time of day or situation (physical activity, illness, etc.) [3,8].                                                                                                      

Today, the insulin pump is one of the most reliable and effective treatments for type 1 diabetes. It helps improve the quality of life of people with diabetes by providing optimal blood glucose control and limiting the risk of Hypoglycaemia [3].

New treatment perspectives

Artificial pancreas

As self-management of type 1 diabetes remains difficult and restrictive, demand for developing closed-loop insulin therapy systems has grown considerably.

The first clinical studies showing the reliability of such devices were carried out in 2010 [10]. However, it was not until 2017 that the first device, incorrectly referred to as an artificial pancreas, was approved following non-randomised clinical trials [5].                                                    

It is not a transplantable artificial organ but a bundle of sophisticated technology combining a continuous glucose monitoring device (CGM), an external insulin pump, and a control unit (sometimes a smartphone) [10].

The results obtained are very encouraging. Clinical studies have shown that the use of an “artificial pancreas” (hybrid-closed loop therapy) increases the proportion of time spent within the optimal blood glucose range by 10%, reduces the time spent in Hypoglycaemia by half, and improves HbA1c (glycated haemoglobin) by 0.3 % [5].

Given its effectiveness, the “artificial pancreas” may well establish itself shortly as the standard treatment for type 1 diabetes [5]. The quality of life of people 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 their eating habits [10].                                                                                                                                                                                                       

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 cells [2]   
• transplantation of a pancreas from a donor [6].   

However, these two 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, which often causes a considerable number of side effects [6].

To overcome these obstacles, international research teams have been developing the technique of using the patient's pluripotent stem cells as a base for generating unlimited insulin-producing cells [6].

Over the past decade, remarkable progress has been made in generating functional beta-pancreatic cells from human stem cells. However, the patient’s immune system attacks the transplanted pancreatic cells [6].   

To prevent the chances of success of this treatment from being compromised by rejection, laboratories are currently working on several solutions using encapsulation technology, immune modulation approaches, and gene editing techniques [6].

Insulin pills

International teams of researchers have been working for several decades on the development of an insulin-based pill to spare people with type 1 diabetes their daily insulin injections while also making it easier for them to adhere to their treatment programs [7].

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 (digested) 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 [7,9].                                                           

More recent experimental work has been carried out on capsules containing insulin in suspension in an ionic liquid coated with acid-resistant molecules. Following initial positive results, researchers must now carry out preclinical tests proving the pills long-term non-toxicity [7].                                                                                                                          

Other researchers have developed a capsule capable of injecting insulin into the stomach lining using a microneedle to avoid perforation [9].

Today, other formats of insulin pills 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 living with type 1 diabetes [7].                                                                                                                                        

Immunotherapy treatment: towards a diabetes vaccine

Type 1 diabetes is an autoimmune disease [2,11] that causes the gradual destruction of insulin-producing beta cells [2].

The underlying concept behind developing a diabetes vaccine is preventing the immune system from attacking the remaining pancreatic cells so that insulin production continues [2].

Over the past ten years, nearly 70 clinical studies have tested the effectiveness of various immunotherapy approaches capable of attenuating the autoimmune reaction specific to type 1 diabetes [11].

One of the most promising avenues for developing a diabetes vaccine is using anti-CD3 monoclonal antibodies [2]. This antibody reduces the loss of functional beta-pancreatic cells as late as seven years after the onset of type 1 diabetes [11].                                                                                                  

A recent clinical study showed that administering anti-CD3 antibodies to family members of people with type 1 diabetes, who are therefore at high risk of developing the condition themselves, slowed its progression by an average of two years [2]. Could the dream of an effective diabetes vaccine become a reality?