A FORUM TO

TYPE 1 DIABETES MELLITUS

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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

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


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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
 

Review Paper: Vaccines For Type 1 Diabetes: Prevention Or Reversal?

Abstract: Type 1 diabetes mellitus (T1DM) is an autoimmune disease which leads to destruction of pancreatic β-cells, thereby causing insufficient insulin production. Globally, around 98, 200 children and adolescents below 15 years of age and almost 128,900 subjects below 20 years of age develop T1DM annually, along with severe complications deteriorating their quality of life. In India alone, around 15,900 incident cases below 15 years have reported annually. Hence, its prevention and reversal are significant. Unlike other chronic diseases, T1DM involves the presence of various autoantigens which can be targeted by proper immunisation. The development of reliable immuno-regulatory surrogate markers would be of a great benefit. Vaccines can be one of such strategies in the journey to prevent T1DM. It would not only benefit greatly to reduce the sufferings caused due to diabetic complications but could also help to reverse T1DM, by modulating the immunological autoantigenic reactions and prevent further degradation of pancreatic β-cells. This review collates a wide range of information related to the vaccine studies conducted in animal and human models to prevent and reverse T1DM. 




Journal: Current Diabetes Reviews 

Keywords: Antigen vaccine; BCG vaccine; Immunomodulation; Micro-organisms; Type 1 diabetes mellitus; Vaccine 

Review Paper: A Peripheral Concept On Aetiology Of Type 1 Diabetes Mellitus

Abstract: Diabetes mellitus is a common metabolic disorder affecting a wide range of population worldwide. There are many types of diabetes mellitus, one of which is type 1 diabetes mellitus (T1DM). It is an autoimmune disorder caused in about 97,700 children in India and 490,000 children globally. Many etiological factors contribute to this disease. This review article is a collage of etiological factors causing T1DM. A better understanding of the aetiology is significant for prevention and management of the disease.


Journal
: Pharmaceutical Resonance 

Keywords: Type 1 Diabetes Mellitus; Etiology; Autoantibodies; Extracellular matrix; Coxsackievirus B virus

Review Paper: Mapping Of Type 1 Diabetes Mellitus

Abstract: Type 1 diabetes mellitus (T1DM), an autoimmune disorder, is becoming widespread with approximately 97,700 children in India and 490,000 children worldwide affected. There are various etiological factors contributing to the expansion of its incidence in different geographical locations. Hence, the articles published in reputed journals were studies and data was collected for analyzing etiology and prevention of T1DM. It has been observed that hybrid insulin peptides act as key antigens for the autoreactive T cells and causes loss of self-tolerance in humans. The association of coxsackievirus B has been observed with the onset of T1DM. Accurate identification of the trigger can lead to the development of appropriate preventive measures. It can become a base for advance studies to prevent T1DM in humans. This review will highlight the causes and some preventive actions which can be considered to eliminate T1DM.


Journal: Current Diabetes Reviews

Keywords: Type 1 diabetes mellitus; coxsackievirus B virus; etiology; pathogenesis; prevention

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Trigger For T1DM: A Research Map

Scientists have identified the possible trigger for type 1 diabetes mellitus (T1DM).

The T cells of the immune system do not recognise self-antigens, i.e., the body’s own cells. Therefore, they are protected from the attack of the immune system. In T1DM and other autoimmune disorders, this protective system gets disrupted1.


Dr Delong and his colleagues carried out an experiment to study the trigger in T1DM. They isolated T cells from a T1DM mouse model and determined the trigger that is recognised as a foreign body in the insulin-producing β-cells. They recognised a modified version of insulin which acted as an antigen. They also observed that the immune T cells from pancreatic islets of two organ donors with T1DM recognised hybrid insulin peptides (HIPs). This study concluded that these HIPs may have a significant role as a trigger to the immune system and hence attack the body’s insulin-producing pancreatic β-cells, and thus causing T1DM1. Antibodies from the blood of T1DM patients recognised the HIPs in the mouse. This suggests that a human equivalent may also exist.

Type 1 Diabetes Mellitus: Aetiology And Pathogenesis

T1DM is allied with the selective destruction of insulin-producing β-cells in the pancreas. The commencement of clinical disease signifies the end stage of β-cell destruction which leads to T1DM. There is marked heterogeneity of the pancreatic lesions, which makes it difficult to follow the pathogenesis of selective β-cell destruction within the islet in T1DM1.


Type 1 Diabetes Mellitus: An Alarming Condition

Diabetes mellitus (DM), a metabolic disorder, is mainly of two types. Type 1 Diabetes Mellitus (T1DM), insulin dependent DM, is an autoimmune reaction to proteins of the islet cells of the pancreas. There is a lack of insulin secretion by β- cells of the pancreas. Type 2 Diabetes Mellitus (T2DM), non-insulin dependent DM, is a combination of genetic factors related to impaired insulin secretion, insulin resistance and environmental factors such as obesity, overeating, lack of exercise, stress, ageing. There is a decreased sensitivity of target tissues to insulin1.

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