As much as an infectious disease spreading across the world, diabetes has become a pandemic in its own right. Although, it is a non-communicable disease, it affects thousands of individuals worldwide bringing about death and other diabetes-related complications to many.
In the year 2019 alone, there were nearly 463 million adults within 20-79 years of age living with diabetes and the experts predict that this will continue to rise to an alarming 700 million by 2045.(1)
A majority of the affected individuals are living in low- and middle-income countries. Therefore, it is equally important that all the treatment options available should fairly reach every part of the world in the same manner.
Nearly a century has passed since the groundbreaking discovery of insulin in 1921 as a treatment modality for diabetes mellitus. One would think with decades of research and experimenting behind us, we must have discovered some way or another to cure diabetes for good by now.
But, quite sadly, it is not entirely the case; a definitive cure for diabetes still remains elusive. However, science is making greater strides towards discovering more promising treatment modalities than ever before.
Here we are trying to look into some of the latest advances in science which hold greater promise in bringing us closer to a cure for diabetes for good. Let’s dive in.
Table of Contents
Type-1 diabetes
Type-1 diabetes mellitus is a condition in which the pancreas fails to produce the necessary amounts of insulin required by the body. This condition typically manifests in childhood, but can present at any stage of life.
The culprit behind type1 diabetes detected?
In type-1 diabetes, the immune system of the body attacks insulin-producing beta cells in the pancreas and destroys them. This process is hence known to be autoimmune in nature.
Although scientists believe various genetic and environmental causes are mainly behind this process, a clear picture regarding the exact mechanism remained a bit blurred, at least until now.
A group of scientists were able to identify a special type of protein called, Hybrid Insulin Peptides (HIP) on the surface of beta cells in the pancreas, of individuals with Type-1 diabetes.(2)
These proteins tag beta cells in the pancreas and highlight them as foreign, making it easier for the immune cells of the body to identify and attack them.
What is more interesting is that even after the onset of diabetes, these immune cells which target HIP-tagged beta cells in the pancreas continue to remain in the blood indicating the presence of autoimmunity in the body.
The discovery of this new protein paves the way for implementing a new therapeutic intervention. If by some means or another the production of HIP proteins could be stopped, it will most likely stop immune cells from attacking pancreatic beta cells in the first place.
Scientists are following the trail of this discovery to implement a brand-new treatment modality to cure Type-1 diabetes in the future.
Stem Cell Research
Destruction of pancreatic beta cells is the main issue behind Type-1 diabetes. To make things even worse, beta cells usually have a very limited ability to procreate or to make new cells replenishing the depleted ones.
Therefore, apart from preserving already functioning beta cells, reprogramming other types of cells to secrete insulin in response to glucose levels in the blood stream has become a hot research topic at the moment.
Scientists are trying to make use of stem cells, a type of cells which have the potential to turn into many forms of cells in the human body, to create a substitute for beta cells in the pancreas.
These stem cells are grown inside the labs and they can be used in islet cell transplants to treat diabetes mellitus.
Scientists are also trying to make use of alpha cells in the pancreas to get them to do the same function as the beta cells, which is secreting insulin. These alpha cells routinely participate in maintaining plasma glucose levels during the fasting phase by producing glucagon.
As both alpha and beta cells have developmental similarities and are located in the same pancreatic islets, this process becomes much easier. Studies show that alpha cells are also capable of producing insulin in a regulated manner in response to insulin insufficiency in the blood, opposite to an uncontrolled or spontaneous way. This is a huge plus point as far as a diabetic treatment option is considered.(3)
A novel way of preventing immune cells from attacking beta cells
A key challenge encountered in replacing beta cells in the pancreas in form of islet cell transplant is the persistent autoimmune attack on the newly introduced cells. Since the autoimmune antibodies continue to exist in the blood, they start to identify newly transplanted beta cells as foreign as well.
To overcome this immune attack, modulating the immune system in the body or subjecting the individual to immunotherapy becomes crucial.
Recently a group of scientists have discovered a novel way to overcome this problem. They make use of regulatory type of T-cells in the body, also called Tregs, which have an immunosuppressive action, for this purpose.
Researchers develop autoantigen-specific Tregs from pluripotent stem cells in labs and program them in such a way as to suppress the autoimmunity process within the body and to down-regulate inflammation in the tissues.(4)
With this method, they have been able to suppress the migration and activity of the pathogenic immune cells which are responsible for causing Type-1 diabetes.
Another similar study reveals that with the use of IgM derived from healthy human donors, the new-onset diabetes can be reversed, while eliminating autoreactive B lymphocytes, and enhancing regulatory T-cell (Treg) numbers.(5)
These findings mark a breakthrough in treating Type-1 diabetes as it allows a higher success rate with pancreatic beta-cell transplantation and provides a good chance of reversing the condition for patients.
Artificial Pancreas
One of the most exciting recent findings as far as treating diabetes is considered is the implementation of an artificial pancreas system that mimics the physiological functions of the pancreas better than any other technology available at the moment.
This novel method is known as the “closed-loop control” and it includes a system that continuously monitors blood glucose. This continuous monitoring system is an important addition which most previous models lacked in them.(6)
As a result of continuous monitoring, the artificial pancreas can release insulin using an in-built pump into the blood to suit the varying requirements of the body. This system replaces the previous tedious monitoring system which included frequent finger pricking and is a great alternative for daily insulin injections.
Type-2 Diabetes
With increasing prevalence of affluent dietary habits and obesity, Type-2 diabetes mellitus has become a common disease condition worldwide. Abnormalities in insulin secretion and action are the hallmarks of this particular type of diabetes.
A combination of genetic predisposition, environmental factors and inflammation in the body increases the susceptibility of getting the disease.
A new way to overcome insulin resistance
Despite years of research, pinpointing the exact cause behind insulin resistance in individuals with Type-2 diabetes has remained elusive. However, a recent study sheds a bit of light on this dilemma.
Studies show that a molecule called ceramide, a product of fat and protein metabolism, to be one of the causes behind insulin resistance and many other metabolic disorders like heart disease and hepatic steatosis.
In a recent study, a group of scientists were able to observe that ceramide could promote lipid uptake and storage by the liver while impairing glucose utilization.(7) It is believed that the enzyme called dihydroceramide desaturase-1, which is involved in the production of ceramide to be the culprit behind insulin resistance.
Animal studies show that by deleting the gene responsible for this particular enzyme, glucose and lipid metabolism can be improved. Therefore, scientists are now developing ways to inhibit the enzyme and decrease ceramide production as it can be utilized as a treatment modality for metabolic diseases including diabetes mellitus.
Making use of the gut microbiome
The tiny microorganisms living in the gut seem to affect our health more than we account them for. They are linked with many diseases including heart disease and diabetes mellitus. Although not every bacterium living in the gut is pathogenic, there exist a few pathogenic bacteria that could cause trouble and they are usually mingled among the rest.
Studies show that some metabolites produced by the gut microbiome like imidazole propionate have the potential to alter insulin sensitivity and glucose metabolism.(8)
Further studies are carried out to explore the possible pharmacological targets based on the microbiome-dependent electrolytes which could be used in the development of future medications for diabetes.
A new insight on a familiar drug- Metformin
Metformin is one of the oldest, not to mention the commonest first-line drug used for treating diabetes around the world at the moment. It acts by inhibiting the glucose production by the liver and also by increasing insulin sensitivity.
In order to lower hepatic glucose production, metformin increases the 5′-adenosine monophosphate (AMP) levels in the body. For this purpose, metformin induces a bit of a stress state in the liver as it promotes the production of AMP.
This AMP in turn inhibits the action of an enzyme called fructose-1,6-bisphosphatase-1 (FBP1), a rate controlling enzyme in gluconeogenesis, which is needed for the liver to produce glucose.
However, in some individuals a point mutation can occur in this FBP1 enzyme, rendering them insensitive to the metformin treatment.
Therefore, scientists are now trying to apply this knowledge clinically, to develop drugs which target inhibition of the FBP1 enzyme directly as a means of controlling blood glucose levels.
A tissue-specific drug delivery system
Researchers manifest a great deal of scientific interest in identifying systemic factors that integrate the individual organ response within the entire body; especially of different types of proteins that participate in body glucose or energy homeostasis.
Recently a group of scientists were able to discover an extracellular vesicle-mediated signaling system that prevail between different cell types within the adipose tissue. This finding has a clinical implication in treating diabetes mellitus as well.
It is believed that this discovery can be applied in developing a more effective tissue-specific drug delivery system by making use of endogenous extracellular vesicles or biosynthetic vesicles to treat diabetes.(3)
The Future of diabetic treatment
Diabetes-related technology evolves by great strides every day. The financial market based on diabetes is expected to make more billions of dollars than it does now in a couple of years into the future. Increasing statistics of Type-1 and Type-2 diabetic individuals across the globe seem to accelerate the process at an unprecedented rate.
Scientists are speculating novel ways to tackle diabetes in a more hassle-free and patient-friendly manner from diagnosis to the very end of the course of management.
New modalities are being developed to diagnose and monitor diabetes without the painful old methods like frequent finger pricks. Making use of electromagnetic waves and laser beams to detect blood glucose levels instead of invasive methods are a few of the latest scientific developments that have gained popularity in recent times.
One of the research organizations is developing a skin patch which has the ability to provide accurate blood glucose level readings by measuring the sugar concentration in multiple hair follicles at the same time. Some skin patches can be worn for even a period of two weeks to obtain continuous glucose monitoring.
As far as the treatment modalities are considered, they are advancing to keep on par with the latest technologies available. Scientists are in the process of developing microchips which can detect diabetes even before the onset of symptoms.
Not only that, they are incorporating nano-technology into treating diabetes too. Developing nanorobots that can travel in the bloodstream while continuously monitoring blood glucose levels on top of administering insulin levels when and where needed is one of the most exciting recent advances ever.
Although these latest developments are not yet in use at a full-blown level, they hold a great deal of promise and excitement regarding the future of diabetic treatment.
With the advancement of science and technology, we have gained more insight into how diabetes works as a disease. New mechanisms are uncovered, new pharmacological targets are identified and sophisticated treatment modalities are being developed each and every day. Therefore, it is safe to say that achieving a definitive cure for either type of diabetes mellitus is not very far down the line at all.
References
1. Facts & figures [Internet]. [cited 2021 Feb 12]. Available from: https://www.idf.org/aboutdiabetes/what-is-diabetes/facts-figures.html
2. Baker RL, Rihanek M, Hohenstein AC, Nakayama M, Michels A, Gottlieb PA, et al. Hybrid insulin peptides are autoantigens in type 1 diabetes. In: Diabetes [Internet]. American Diabetes Association Inc.; 2019 [cited 2021 Feb 23]. p. 1830–40. Available from: https://doi.org/10.2337/db19-0128
3. Zierath JR. Major Advances and Discoveries in Diabetes – 2019 in Review [Internet]. Vol. 19, Current Diabetes Reports. Current Medicine Group LLC 1; 2019 [cited 2021 Feb 23]. p. 1–9. Available from: https://doi.org/10.1007/s11892-019-1255-x
4. Haque M, Lei F, Xiong X, Das JK, Ren X, Fang D, et al. Stem cell-derived tissue-associated regulatory T cells suppress the activity of pathogenic cells in autoimmune diabetes. JCI Insight [Internet]. 2019 Apr 4 [cited 2021 Feb 22];4(7). Available from: https://doi.org/10.1172/jci.insight.126471:e126471.https://doi.org/10.1172/jci.insight.126471.
5. Wilson CS, Chhabra P, Marshall AF, Morr C V., Stocks BT, Hoopes EM, et al. Healthy donor polyclonal IgMS diminish B-lymphocyte autoreactivity, enhance regulatory T-cell generation, and reverse type 1 diabetes in NOD mice. In: Diabetes [Internet]. American Diabetes Association Inc.; 2018 [cited 2021 Feb 22]. p. 2349–60. Available from: https://doi.org/10.2337/db18-0456
6. Brown SA, Kovatchev BP, Raghinaru D, Lum JW, Buckingham BA, Kudva YC, et al. Six-Month Randomized, Multicenter Trial of Closed-Loop Control in Type 1 Diabetes. N Engl J Med [Internet]. 2019 Oct 31 [cited 2021 Feb 26];381(18):1707–17. Available from: http://www.nejm.org/doi/10.1056/NEJMoa1907863
7. Chaurasia B, Tippetts TS, Monibas RM, Liu J, Li Y, Wang L, et al. Targeting a ceramide double bond improves insulin resistance and hepatic steatosis. Science (80- ) [Internet]. 2019 Jul 26 [cited 2021 Feb 26];365(6451):386–92. Available from: http://science.sciencemag.org/
8. Koh A, Molinaro A, Ståhlman M, Khan MT, Schmidt C, Mannerås-Holm L, et al. Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1. Cell. 2018;175(4):947-961.e17.