A FORUM TO

TYPE 1 DIABETES MELLITUS

image
A Step Into Freedom From Type 1 Diabetes

T1DM.org

T1DM.org is a platform which consolidates the author’s work about type 1 diabetes and its management. This forum invites an open interaction from national and international experts to manage type 1 diabetes, share their knowledge and collaborate to work towards freedom from this painful disease.

This forum only includes the papers published by the author in the journals of repute at the moment. These papers primarily involve the content related to the etiology and pathophysiology of T1DM, application of mesenchymal stem cells to manage T1DM and improve the quality of life in patients, and about the correlation of diabetes with hepatic dysfunctions. However, it will soon come up with the papers related to the immunomodulatory aspects in the journey to prevent and reverse the disease.

With more interaction and collaborations, we can bring an end to T1DM and give a better life to the children who are at risk to develop this immensely agonising disease.

OUR APPROACH

1. In-vitro Study

Test the immunological reactions

2. Preclinical Study

Test the immunological responses in animal model

3. Formulation

Prepare a potential formulation candidate based on results and tests in in-vivo

4. Clinical Study

Clinical evaluation of the potential formation for T1DM
OUR T1DM PUBLICATIONS

[Video] What is Type 1 Diabetes Mellitus?


The history of type 1 diabetes mellitus (T1DM) is a longstanding story and during this 'Diabetes Month' we have designed this platform to discuss various aspects of this disease. This video is an introduction to T1DM on the occasion of Diabetes Day 2021.



For more publications and discussions on type 1 diabetes, visit T1DM.org.


For queries or feedback, email to info@t1dm.org or simply leave a comment below.

Seesaw of Th1 and Th2 in Autoimmune Disorders

Autoimmune diseases stem from imbalances within the functioning of the patient’s immune system. This imbalance is witnessed due to many factors, such as stress, malnutrition, vitamin and mineral deficiencies, inappropriate gut flora, and allergies. These are the common etiologies that are considered while diagnosing any autoimmune disease. 

However, this article describes the basic explanation about the mechanism of T-helper (Th) cells disturbing the immune system, as well as the factors causing this imbalance.

What are Th1 and Th2?

T-helper cells (Th) are an important part of the immune system. They are lymphocytes that recognize foreign pathogens or normal tissues in autoimmune diseases. Cytokines are produced as a response. These Th cells are divided into subgroups:

Th1

Th2

Involved in “cell-mediated” immunity

Involved in “humoral-mediated” immunity

Usually deals with infections by viruses and certain bacteria

Usually deals with infections by bacteria, toxins, and allergens

Body’s first line of defense against pathogens that get inside our cells

Stimulating the production of antibodies in response to extracellular pathogens (those found in blood or other body fluids)

Tend to be pro-inflammatory

Tend to be anti-inflammatory

Involved in the development of organ-specific autoimmune disease

Involved in systemic autoimmune disease and other chronic conditions


In a well-functioning immune system, both groups of these T helper cells work together to keep the system balanced. One side might become more active to eradicate a threat, then settling back to a balanced level. 

Effect of Th Responses in Autoimmune Disease


An alteration in Th1-Th2 balance causes various autoimmune diseases. This is described in the figure.


When the Th1 cells of the immune system are overactive, they can suppress the activity of Th2 and vice versa. This can be problematic, because these two components of the immune system function in a delicately balanced relationship. In the case of autoimmune disease, an imbalance can further the attack on healthy tissue, thereby worsening symptoms. 

Maintaining a balance between Th1 and Th2 immunological responses is paramount to healthy immune functionality.

[Review Paper] Type 1 Diabetes and Covid-19: Managing the Difficult Duo

Coronavirus disease 2019 (COVID-19) has stimulated health concerns globally, especially in diabetes where it has been accompanied by severe outcomes.

Type 2 diabetes mellitus (T2DM) is a chief worry; though, there are a considerable population of patients with type 1 diabetes mellitus (T1DM) also, that too with incomparable concerns during the current COVID-19 pandemic. Some children experience significant complications related to this disease and paediatric deaths have also been reported.

This article describes some key points related to the complications and management of concomitant T1DM and COVID-19.

A Century-long Journey of Type 1 Diabetes Management: From Insulin to …???

Can you answer this question mark in the title? What is the next product coming in the market for reversing or managing type 1 diabetes?

The history of type 1 diabetes (T1DM) is a longstanding story. However, its management became possible only after the discovery of insulin by Frederick Banting and Charles Best in 1921. With this, scientists started developing the hopes to cure this disease. Unfortunately, this goal is yet to be accomplished. This article gives a tour of the various advancements in managing T1DM and how still there is no cure for this perilous disease.
Insulin: The First Weapon to Fight T1DM

The discovery of insulin was not by chance, it was a very well-thought science. The cascade goes as follows:

1889: Joseph von Mering and Oskar Minkowski observed that removing the pancreas from dogs developed diabetes in them, followed by their death shortly.

1910: Sir Edward Albert Sharpey-Schafer projected that the lack of a specific chemical produced by the pancreas is responsible for the development of diabetes. He then named it 'insulin'.

1921: Frederick Banting and Charles Best extracted the pancreatic islet cells from healthy dogs and presented them into the dogs with diabetes which reversed the diabetic condition. This was a stepping stone towards the management of T1DM by the discovery of the hormone, insulin.

Then with the help of two other scientists, then purified insulin extracted from the cow’s pancreas and marked the first treatment option for diabetes.

Finally, in January 1922, this research was translated to humans when 14-year-old Leonard Thompson received an insulin injection to treat his diabetes. This helped him survive for 13 more years and eventually, he died of pneumonia.

And the journey continues this way…

1930s: Introduction of Insulins with longer duration of action.

1936: Sir Harold Percival Himsworth published his research which helped to understand the difference between type 1 diabetes and type 2 diabetes.

1978: Development of Humulin, the first human-based insulin, identical to human insulin in structure.

1986: Insulin pen (prefilled syringes) delivery system was available. This lead to a safe and convenient way to deliver the required dose of insulin.

1990s: Invention of external insulin pumps, which could provide healthier results, more flexibility, and easier treatment management.

1996: Lispro, the first short-acting insulin (onset of action = 15 minutes and duration of action = 2-4 hours), entered the market.

Where We Are Today

Insulin is still the only therapy used to manage type 1 diabetes. Islet transplant is also considered; however, it has to be accompanied with immunosuppressant drugs and still there is difficulty in maintenance of insulin independence; plus, Cadaveric islet transplantation needs multiple donors and is non-affordable to the common man. Extensive research is going on for immune-related therapies; unfortunately, with nothing in the market yet for patient us.

We are working towards a permanent solution to prevent and reverse type 1 diabetes and looking forward to eradicating this disease.

Type 1 to Type None!

References
  1. Vecchio I, Tornali C, Bragazzi NL, Martini M. The Discovery of Insulin: An Important Milestone in the History of Medicine. Front Endocrinol (Lausanne). 2018; 9:613.
  2. Subramanian S, Baidal D, Skyler JS, Hirsch IB. The Management of Type 1 Diabetes. [Updated 2016 Nov 16]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279114/
  3. Raz I., Ziegler A.G., Linn T. et al. Treatment of Recent-Onset Type 1 Diabetic Patients With DiaPep277: Results of a Double-Blind, Placebo Controlled, Randomized Phase 3 Trial. Diabetes Care. 2014; 37:1392-1400.
  4. Kühtreiber W.M., Tran L., Kim T. et al. Long-term reduction in hyperglycemia in advanced type 1 diabetes: the value of induced aerobic glycolysis with BCG vaccinations. npj Vaccines. 2018; 23:1-14.


[Review Paper] Polyvaccine - Joining The Links In The Cascade Of Type 1 Diabetes

Abstract: The incidence of type 1 diabetes mellitus (T1DM), an autoimmune disorder, has ascended considerably with around 98,200 and 15,900 incidents in children below 15 years of age, globally and in India, respectively. This is typically due to environmental changes leading to genetic modifications. Also, T1DM encompasses the presence of autoantigens and many other etiologies which can be targeted by proper immunization. In this paper, we consciously discuss and collate various candidate triggers of islet autoimmunity and other factors expected to promote the progression of T1DM. This paper bridges all the mechanisms caused by these factors and linking them with each other. We have also highlighted the novel coronavirus as a trigger for T1DM. Finally, we suggest that an amalgamated model of polyvaccine can batter the condition by inducing protection against various triggers of T1DM.

Journal: Clinical and Experimental Vaccine Research 


Keywords: Type 1 diabetes mellitus; Viruses; Coronavirus; Cow's milk; Hybrid insulin peptides; Vaccines


Read Full Review Paper



[Review Paper] Stem Cells - A Golden Therapy for Diabetic Wound

Abstract: Diabetes mellitus is the 7th leading cause of death worldwide. Diabetes can affect the organ systems and lead to a serious complication, majorly categorized as macrovascular complications, microvascular complications, and diabetic wound. Foot ulcer develops in 15-25% diabetic patient. In diabetic wound, there is impairment in growth factor, neuropeptide, matrix metalloproteinases, angiogenesis, immune system. Many approaches are being experimented to manage this major complication of the diabetic foot, but unfortunately with lesser success rate. A stem cell is an upcoming field which is being explored in the world of diabetes. Hence, this review is designed to understand the basic pathogenesis and complications of types of diabetes and the role of stem cells in the diabetic wound and the benefits related to it.


Journal: Current Diabetes Reviews 


Keywords: Angiogenesis; Diabetes mellitus; Diabetic complications; Foot ulcer; Stem cells


Read Full Review Paper



[Review Paper] Antibiotics - A Boon Or Tragedy For Type 1 Diabetes?

Abstract: Type 1 diabetes mellitus (T1DM), an autoimmune disease, leads to obliteration of
pancreatic β-cells, and hence causes insufficient production of insulin. With many other etiological factors, antibiotic use and gut microbiota have a significant role to play in its development. The gut microbiota interacts with the cells involved in innate immunity and has a significant role in determining the immune system. Several factors such as mode of birth, infections, diet, and medication including antibiotics influence the microbiota composition. Alterations and manipulation of microbiota in animal models have shown to affect the onset and incidence of disease having multifactorial etiology, like T1DM. Hence, the microbiota is an integral part which influences the innate immune cells and this microbiota is influenced by the use of antibiotics. This review discusses the studies in relation to the microbiota and antibiotic use with reference to T1DM.




Journal: Pharmaceutical Resonance 

Keywords: Type 1 diabetes mellitus; Antibiotics; Microbiota; Innate immunity

[Review Paper] Wound With Diabetes - Present Scenario And Future

Abstract: Diabetes is a chronic metabolic disorder of the endocrine system characterized by an increase in blood glucose level. Several factors such as pancreatic damage, oxidative stress, infection, genetic factor, obesity, liver dysfunction play a vital role in the pathogenesis of diabetes which further leads to serious diabetic complications. The diabetic wound is one such complication where the wound formation occurs, especially due to pressure and its healing process is disrupted due to factors such as hyperglycemia, neuropathy, nephropathy, peripheral vascular disease, reduction of blood flow, atherosclerosis, impaired fibroblast. Process of wound healing is delayed due to different abnormalities like alteration in nitric oxide level, increase in aldose reductase, sorbitol and fructose. Therefore, diabetic wound requires more time to heal as compared to a normal wound. Healing time is delayed in diabetic wound due to many factors such as stress, decreased oxygenation supply, infection, decreased blood flow, impaired proliferation and migration rate, impaired growth factor production, impaired keratinocytes proliferation and migration, and altered vascular endothelial mediators. The current treatment for diabetic wound includes wound patches, oxygenation therapy, hydrogel patches, gene therapy, laser therapy, and stem cell therapy. Medications with phytoconstituents are also one way to manage the diabetic wound, but it is not more effective for quick healing. The objective of this review is to understand the potential of various management options which are available for diabetic wound, with a special focus on biological cells.




Journal: Current Diabetes Review

Keywords: Angiogenesis; Diabetic wound; Growth factors; Stem cells; Wound healing

[Review Paper] Treat Liver To Beat Diabetes

Abstract: Management of Type 2 Diabetes (T2DM) with existing strategies of lifestyle and pharmaceutical interventions has gained limited success as evidenced by its uncontrolled progression. Two key organs which are involved in the pathophysiology of T2DM are liver and pancreas, both are the derivatives of endoderm with a common precursor. In the invertebrates, hepatopancreas performs the function of both liver and pancreas. It is known that derangement in glycolysis, neoglucogenesis, and glycogenolysis lead to hyperglycemia in T2DM although insulin levels are high. Several studies have reported the implication of abnormal liver function in the development of metabolic syndrome i.e. T2DM. Partial hepatectomy has been shown to improve glycemic status in animal models of diabetes. This could be because liver and pancreas share the same regenerating factors. These evidences suggest that abnormal liver status can impair pancreatic beta-cell function and survival along with peripheral insulin resistance. We, therefore, hypothesize that restoring deranged liver functions may aid in the better control and management of T2DM. If found true, it may shift the current intervention strategy towards liver rather than pancreas in the treatment of T2DM.



Journal: Medical Hypotheses

Keywords: Type 2 Diabetes, Liver dysfunction, Pancreas, Intra-organ communication
 

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Dr Shivani Desai
+91-20-49300148
Pune, India