Is It Possible To Cure Diabetes In The Future?

Diabetes:- Diabetes occurs when the body’s blood glucose (a primary source of energy and comes from the food that you eat) level is elevated. It usually refers to Diabetes Mellitus and leads to severe damage to various organs like the heart, blood vessels, eyes, kidneys, and nerves over time. Type-1(insulin-dependent or childhood-onset) and Type-2(adult-onset or noninsulin-dependent) diabetes are the most common among all diabetes types. Other types of diabetes are Gestational Diabetes, Diabetes Insipidus, Monogenic diabetes, etc. 90-95% of all diabetic patients are of type-2 diabetes.^1,2

In the 21st century, diabetes is the fastest growing global health emergency. According to the study, it is estimated that about 463 million people had diabetes worldwide in 2019, and this number is projected to reach 578 million by 2030 and 700 million by 2045. The World Health Organization considered diabetes an epidemic and predicts that it will be the seventh biggest reason of death worldwide soon.^3,4

In this article, Section-1 will discuss current available treatments and problems associated with type-1 and type-2 diabetes. Section-2 will discuss the future of diabetes with specific focus to various target areas on which the researcher is working to cure diabetes.

SECTION 1.1: Type-1 Diabetes: – Insulin with short-acting, regular acting, intermediate-acting, and long-acting dose ranges is used nowadays for type-1 diabetes treatment. Other than this, Immunotherapy, Metformin, Blood sugar drugs, Cholesterols drugs and Aspirin, etc. are the available treatment.⁵

Problem with current therapy for Treating Diabetes Type 1: – These therapies are only acting against the events that occur due to disease. These therapies have no role in actually preventing or altering the pathophysiology of the disease. The main goal in treating diabetes involves the prevention or decreasing rate of the autoimmune process of beta-cell destruction.

SECTION 1.2: Type-2 Diabetes: – Treatment includes Metformin, Sulfonylureas, Meglitinides, Thiazolidinediones, DPP-4 Inhibitors, SGLT-2 Inhibitors, GLP-1 Agonist and Insulin, etc.⁶

The Problem Associated With Current Therapy For Treating Diabetes Type 2: – Most of the drug therapies available for type-2 diabetes are only to control the diabetic condition and not cure the disease. Every drug used in Type-2 diabetes treatment has some side effects and affects various organs in the long term. For example, Sulfonylureas have side effects such as weight gain and hypoglycemia. Kidney complications are associated with Metformin. Thiazolidinediones may cause weight gain, liver diseases, and swelling of legs or ankles.

Whatever will be brought by the future will undoubtedly make a huge difference in millions of lives worldwide. Science strives to find a diabetes treatment that can cure this chronic disease, but the question remains the same “How close are we?” The biotech industry is looking at it as an opportunity and looking to develop new diabetes treatments to cure this chronic disease. Let’s look at the activity going on in this domain and how those activities will change diabetes treatment.^7,8

1. Replacing Missing Cells With Cell Therapy: Replacement of missing insulin-producing cells is the most powerful method for developing a cure for Type-1 diabetes. Most of the big pharma companies are in the early stage of cell therapy. But initial attempts of transplantation have failed due to immune reactions by the recipient body. The recipient body produces an immune response against these pancreatic cells, which reject and destroy the cells. Diabetes Research Institute in the US developed a bioengineered mini-organ in which insulin-producing cells are encapsulated in a protective barrier to tackle the immune reaction problem. Orgenesis is working on an approach where cells from patients are transformed into insulin-producing cells to tackle donors’ problems. One of the largest diabetes treatment providers, i.e., Novo Nordisk, is bidding on stem cell therapy and encapsulation devices.^[8]
2. Automated Treatment With An Artificial Pancreas: A fully automatic system (Artificial Pancreas) that can inject a precise amount of insulin after measuring glucose level is the solution for those who have already lost their insulin-producing cells. It will be a better option for a patient because it could better control glucose levels, and lesser complications will result in the long term. Challenges yet to be addressed are whether algorithms are significant enough to make accurate predictions? Most of the companies are in phase-1 and phase-2 clinical trials for this treatment.⁸
3. Attacking The Origin With Immunotherapy: In type-1 diabetes the immune system progressively destruct the pancreas’ beta cells (responsible for insulin production). By stopping this process, cells can be preserved, and diabetes can be cured. Various companies are working on immunotherapy via the mechanism of action like Anti-IL1, Anti-IL 12/13, TNF-alpha inhibitor, Anti-IL6, etc. Imcyse (a Belgian company) is working on immunotherapy to stop type-1 diabetes by killing the pancreas killer immune cells. Neovacs is working on a vaccine that stimulates the immune system to lower the levels of an inflammatory protein that is thought to be involved in multiple autoimmune diseases. ActoBio is using cheese-producing bacteria to deliver two drugs that stimulate T-regulatory cells.⁸
4. Replace and Regenerate: FOXO1 (a protein that controls when genes are switched on or off) is discovered by Domenico Accili and the team at Columbia University in New York. They found that by deactivation of FOXO1 in progenitor cells in the small intestine of newborn mice results in the cells becoming insulin-producing.

Some companies are also working on gene therapy, combination therapies, etc. but most of the trials are on their earlier phase.⁹

1. Targeting The Microbiome: Human microbiome (Especially Gut microbiome) is linked to multiple chronic diseases, including diabetes. Unbalanced microbiome composition is associated with diabetes. It has been found that diabetes people have less diverse microbiomes as compared to healthy people. Amsterdam University researchers showed that fecal transplants (used to transfer microbiome into the gut of a diabetes patient from a healthy person) could result in a short-term improvement of insulin resistance in an obese patient with type-2 diabetes. French Valviotis is currently on a drug that will increase the microbiome diversity as a type-2 diabetes treatment. The microbiome is very young in this domain, and it will be difficult to measure real potential until more diabetes are tested in clinical trials.8
2. Stimulating Insulin Production: GLP-1 receptor agonist (which induce production in beta cells while suppressing the secretion of glucagon, a hormone with the opposite effect to insulin) is the biggest hit in type-2 diabetes treatment. All big pharma companies like Sanofi, Eli Lilly, Roche, AstraZeneca, etc. have GLP-1 drugs on the shelves of the market or their pipeline bucket. Poxel (French company) is working on a drug that simultaneously targets the pancreas, liver, and muscles to decrease blood sugar. German Morphosys is designing an antibody that reduces fat, prevents insulin resistance, and controls excessive eating.⁸

• Ileal Interposition: It is a metabolic procedure used for overweight, diabetic patients. This surgery will increase the GLP-1 hormone’s secretion, and having success rate ranges between 80%-100% depending upon the post-surgical care. In this technique, the Ileum is placed either between the stomach and the proximal part of the small intestine or by putting it to the small intestine’s proximal portion.¹⁰
• Sleeve Gastrectomy: In this surgery, a larger portion of the stomach is removed to decrease the reservoir of food—this surgery decreases the ‘Ghrelin’ hormone level that makes me feel hungry. Higher than 80% of people show no sign of diabetes after surgery.¹⁰
• Gastric Bypass (Roux-en-Y gastric bypass) Surgery: In this surgery, the stomach size is reduced by stapling off its section. It will decrease the food intake and fat amount and calories that we absorb. Up to 60% of people show no diabetes sign after surgery.¹⁰

Diabetes is a chronic disease that is increasing with an alarming prevalence rate worldwide. The world health organization is also considered as epidemic disease and predicting that it will be the seventh most cause of deaths worldwide.

Researchers are working on various advanced technology and new mechanisms for finding the cure for Diabetes. It can’t be said how close we are to the treatment of diabetes. Most of the clinical trials are in the early stages, but the future can’t be predicted because some of the previous studies did not show good responses with the same approaches as now are going on.

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