Research Article
Volume 4 Issue 6 - 2020
Path Directed towards a Stage when we almost Cure Type1 Diabetes Mellitus (T1dm) after a Century of Insulin Advent
Kulvinder Kochar Kaur1*, Gautam Allahbadia2 and Mandeep Singh3
1Scientific Director, DR Kulvinder Kaur Centre For Human Reproduction, Jalandhar, Punjab, India
2Scientific Director, Rotunda-A Centre for Human reproduction, Mumbai, India
3Consultant Neurologist, Swami Satyanand Hospital, Jalandhar, Punjab, India
*Corresponding Author: Kulvinder Kochar Kaur, Scientific Director, DR Kulvinder Kaur Centre For Human Reproduction, Jalandhar, Punjab, India.
Received: February 22, 2020; Published: May 30, 2020




Abstract

Following the discovery of insulin lives of type 1 diabetes mellitus (T1DM) patients changed dramatically so that what was literally a death warning became a disease that could be controlled although still remaining a chronic disease, with insulin not curing the disease process, rather only its consequences i.e. blood sugars. Noticeably insulin does not achieve normoglycaemia. Despite maximum sophisticated, practically ‘near closed loops’ ways, glucose homeostasis does not get back to normal. Both short as well as long term complications are incurred by T1DM patients, with hypoglycaemic as well as hyperglycaemic events as well as long term effects of enhanced glycosylation of proteins resulting in eye, renal, central nervous system (CNS) as well as other complications. These sequelae are correlated with marked morbidity as well as mortality despite following aggressive insulin treatment. Practically a century after insulin discovery, we still battle with the hurdle of addressing disease process by itself, just to make the life of these patients better. Lot of work have been done to be able to totally arrest the autoimmune mechanism damaging the insulin synthesizing cells within the pancreas, or minimum at least reduce the speed of the process for blunting as well as delaying short as well as long term complications. Basic idea is to discuss a method that might aid in quantitative result measurements by particular therapies, short or clinical cure might be contrasted and exact advantage of their help in DM treatment might get assessed by the T1DM metabolic recovery index (DMMRI).

Keywords: T1DM; Autoimmune Process; Metabolic Checking; DMMRI

References

  1. Banting FG., et al. “Pancreatic Extracts in the treatment of Diabetes Mellitus”. Canadian Medical Association Journal 12 (1922): 141-146.
  2. Thabit H and Hovorka R. “Coming of age :The artificial pancreas fortype1 Diabetes”. Diabetologia 59 (2016): 1795-1805.
  3. Home PD. “Plasma insulin profiles after subcutaneous injection: How close can we get to physiology in people with diabetes?” Diabetes, Obesity and Metabolism 17 (2015): 1011-1020.
  4. De Boer LH., et al. “Long term renal outcomes of patients with type 1 diabetes mellitus and microalbuminurea: An analysis of the diabetes control and complications Trial /Epidemiology of diabetes Interventions and Complications Trial/Epidemiology of diabetes Interventions and complications cohort”. Archives of Internal Medicine 171 (2011): 412-420.
  5. White HN., et al. “Effect of prior intensive therapy in type 1 diabetes on 10year ;progression and retinopathy in the DCCT /EDTC: Comparison of adults and adolescents”. Diabetes 59 (2010): 1244-1253.
  6. Alberts JW., et al. “Effect of prior insulin treatment during the diabetes control and complications Trial(DCCT)on peripheral neuropathy in type 1 diabetes during the Epidemiology of diabetes Interventions and Complications(EDIC) Study”. Diabetes Care 33 (2010): 1090-1096.
  7. Kulvinder Kochar Kaur., et al. “An Update on Etiopathogenesis and Management t of Type 1 Diabetes Mellitus”. Open Access Journal of Endocrinology 1.2 (2017): 1-23.
  8. Kulvinder Kochar Kaur., et al. “Restricting Carbohydrates in the Diet-A Possible Method of Meeting the Challenges of Increasing Diabesity in Type1 Diabetes along with Meeting Exercise Performances Requirements-A Review”. Open Access Journal of Endocrinology 3.1 (2019): 000138. 
  9. Kulvinder Kochar Kaur., et al. “How can we use Empagliflozin as an adjuvant in reducing required need of insulin in type1 diabetes along with lowered HbA1c,weight without fear of DKA.-A Minireview’’. under publication in press accepted (2019).
  10. Kulvinder Kochar Kaur., et al. “An update on the Immunotherapy Strategies for the treatment of Type 1 Diabetes(TID )-How far have we reached in reaching insulin independency in TID therapy.-A Systematic Review’’. Journal of Endocrinology (2020).
  11. Wallberg M and Cooke A. “Immune mechanisms in Type 1 Diabetes”. Trends in Immunology 34.12 (2013): 583-591.
  12. Knip M and Smell O. “Environmental triggers of Type 1 Diabetes”. Cold Spring Harbor Perspectives in Medicine 2.7 (2012): 176-185.
  13. Adamczak DM., et al. “The roll of Toll like receptors and Vitamin D in Diabetes mellitus Type 1-a review”. Scandinavian Journal of Immunology 80.2 (2014): 75-84.
  14. Norris JM., et al. “Timing of initial cereal exposure in infancy and risk of islet autoimmunity”. The Journal of the American Medical Association 290.13 (2003): 1713-1720.
  15. Itoh A and Ridgway WM. “Targeting innate immunity to downregulate adaptive immunity and reverse Type 1 Diabetes and reverse Type 1 Diabetes”. ImmunoTargets and Therapy 6 (2017): 31-38.
  16. Kondrashova A and Hyoty H. “Role of viruses and other microbes in the pathogenesis of Type 1 Diabetes”. International Reviews of Immunology 33.4 (2014): 284-295.
  17. Mojlibian M., et al. “Diabetes specific HLA-DR-restricted proinflammatory T cell response to wheat polypeptides in tissue transglutaminase antibody –negative patients with Type 1 Diabetes”. Diabetes 58.8 (2009): 1789-1796.
  18. Adorini L. “Interventions in autoimmunity: the potential of Vitamin D receptor agonists”. Cellular Immunology 233.2 (2005): 115-124.
  19. Knip M. “Autoimmune mechanism s in Type 1 Diabetes”. Autoimmunity Reviews 7.7 (2008): 550-557.
  20. Zhou Z and Jensen PE. “Structural characteristics of HLA-DQ that may impact DM editing and susceptibility to Type 1 Diabetes”. Frontiers in Immunology 4 (2013): 262.
  21. Wing K., et al. “CTLA-4 control over Foxp3+regulatory T cell function”. Science 322.5899 (2008): 271-275.
  22. Roy Chaudhary R., et al. “BACH2 represses effector programs to stabilize Treg- mediated Immune homeostasis”. Nature 498.7455 (2013): 506-510.
  23. Downes K., et al. “Reduced expression of ifih1 is protective for Type 1 Diabetes”. PLoS One 5.9 (2010): e12469.
  24. Wachlin G., et al. “IL-1β ,IFNƴ and TNFα increase vulnerability of pancreatic beta cells to autoimmune destruction”. Journal of Autoimmunity 20.4 (2003): 303-312.
  25. Marroqli L., et al. “BACH2-a candidate risk gene for Type 1 Diabetes, regulates apoptosis in pancreatic β-cells via JNK 1 modulation and crosstalk with the candidate gene PTPN2”. Diabetes 63.7 (2014): 2516-527.
  26. Naguiera TC., et al. “GLIS3.a susceptibility gene for Type 1 and type2 Diabetes modulates pancreatic β-cells apoptosis via regulation of a splice variant of the BH3-Only protein bim”. PLoS Genetics 9.5 (2013): e1003532.
  27. Kulvinder Kochar Kaur., et al. “An Update on Aetiopathogenesis and Management of Obesity”. Obesity and Control Therapies: Open Access 3.1 (2016): 1-17. 
  28. Kulvinder Kochar Kaur., et al. “Hypothalamic inflammation and glioses as aetiopathogenetic factor inhigh fat diet induced obesity and various therapeutic options to resolve it”. Obesity Research and Clinical Practice Journal 4.2 (2017): 44-60.
  29. Kulvinder Kochar Kaur., et al. “Current advances in pathogenesis in obesity: Role of Hypothaalamic gliosis”. Journal of Obesity and Weight Loss 3.008 (2018): 1-11.
  30. Kulvinder Kochar Kaur., et al. “Have Probiotics and Synbiotics passed the test of time to be implemented in management of obesity and related metabolic disorders-a comprehensive review”. Obesity, Weight Management and Control Advances 9.1 (2019): 21-28. 
  31. Kulvinder Kochar Kaur., et al. “Weight loss Associated with high protein Intake in Obesity:Interactions of Gut Microbiota in Protein Sources influencing this positive effect”. Acta Scientific Nutritional Health 2.7 (2018) : 80-89.
  32. Kulvinder Kochar Kaur., et al. “Will Probiotics Provide the Answer for Therapy of Non-alcoholic Fatty Liver Disease (NAFLD)? – A Systematic Review”. Biochemistry and Physiology 9 (2020): 257.
  33. Depommier C., et al. “Supplementation with Akkermansia muciniphila in overweight and obese human volunteers :A proof of concept exploratory study”. Nature Medicine 25 (2019): 1096-1103.
  34. Giongo A., et al. “Toward defining the autoimmune microbiome for type 1 diabetes”. The ISME Journal 5 (2011): 82-91.
  35. Huang Y., et al. “Gut microbiota profiling in Han Chinese with type 1 diabetes”. Diabetes Research and Clinical Practice 141 (2018): 256-263.
  36. Paun A., et al. “The influence of microbiome on type 1 diabetes”. Journal of Immunology 198 (2017): 590-595.
  37. Kriegel MA., et al. “Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in non obese diabetic mice”. Proceedings of the National Academy of Sciences of the United States of America 108 (2011): 11548-1563.
  38. Parikka V., et al. “Early seroconversion and rapidly increasing autoantibody concentrations predict pubertal prepubertal manifestation of type 1 diabetes in children at genetic risk”. Diabetologia 55 (2012): 1926-1936.
  39. Krischer JP., et al. “The 6 year incidence of diabetes-associated autoantibodies in genetically at risk children: the TEDDY study”. Diabetologia 58 (2015): 980-987.
  40. Bosi E., et al. “Impact of age and antibody type on progression from single to multiple autoantibodies in type 1 diabetes relatives”. The Journal of Clinical Endocrinology and Metabolism 102 (2017): 2881-886.
  41. American Diabetes Association. “2 Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2019”. Diabetes Care 42 (2019): S13-S28.
  42. Herold KC., et al. “Teplizumab(antiCD3mAb) treatment preserves C-peptide responses in patients with new –onset type 1 diabetes in a randomized controlled trial: Metabolic and immunologic features at baseline identify a subgroup of responders”. Diabetes 62 (2013): 3766-3774.
  43. Rigby MR., et al. “Targeting of memory T cells with alefacept in new –onset type 1 diabetes (TIDAL study):12 month results of a randomized, double blind placebo controlled phase 2 trial”. The Lancet Diabetes and Endocrinology 1 (2013): 284-294.
  44. Mahon JL., et al. “The Trial Net Natural History Study of the Development of type 1 diabetes: Objectives, design and initial results”. Pediatrics and Diabetes 10 (2009): 97-104.
  45. Bluestone JA., et al. “Type 1 Diabetes Immunotherapy using polyclonal regulatory T Cells”. Science Translational Medicine 7.315 (2015): 315ra189.
  46. Vaseghi H., et al. “T helper cell type1-Transcription factor T-Bet is downregulated in Type 1Diabetes”. Iranian Journal of Allergy, Asthma and Immunology 15.5 (2016): 386-393.
  47. Eisen barth GS. “Autoimmune beta cell insufficiency”. Triangle 23 (1984): 111-124.
  48. Orban T., et al. “A novel quantitative approach to staging and assessing recovery from type 1 diabetes mellitus: the type 1 diabetes mellitus metabolic recovery index”. International Journal of Molecular Sciences 21 (2020): 992.
  49. Walker LS and Von Herrath. “CDT4 cell differentiation in type 1 diabetes”. Clinical and Experimental Immunology 183 (2016): 16-29.
  50. Bluestone JA., et al. “Type 1 diabetes immunotherapy using polyglonal regulatory T cell”. Science Translational Medicine 7 (2015): 315ra189.
  51. Calderon B., et al. “The central role of antigen presentation in islets of langerhans in autoimmune diabetes”. Current Opinion in Immunology 26 (2014): 32-40.
  52. Abreu JR., et al. “CD8T cell autoreactivity to proinsulin epitopes with very low human leukocyte antigen class1 binding affinity”. Clinical and Experimental Immunology 170 (2012): 57-65.
  53. Gitelman SE., et al. “Antithymocyte globulin treatment for patients with recent onset Type 1 diabetes: 12 mths results of a randomised ,placebo controlled ,phase 2 trial”. The Lancet Diabetes and Endocrinology 1 (2013): 306-316.
  54. Keymeulen SE., et al. “Insulin needs after CD3 –antibody in new onset Type 1 diabetes”. The New England Journal of Medicine 352 (2008): 2598-2608.
  55. Orban T., et al. “Costimulation modulation with abatacept in patients with recent onset Type 1 diabetes: a randomised, double blind , placebo controlled trial”. Lancet 378 (2011): 412-419.
  56. Pescovitz MD., et al. “B lymphocytes depletion and preservation of beta cell function”. The New England Journal of Medicine 361 (2009): 2143-2152.
  57. Brooks-Worrell B., et al. “Intermolecular Antigen Spreading Occurs during the preclinical period of human Type 1 diabetes”. Journal of Immunology 166 (2001): 5265-5270.
  58. Skyler JS., et al. “Effects of oral insulin in relatives of patients with diabetes :The diabetes prevention trial- Type 1”. Diabetes Care 28 (2005): 1068-1976.
  59. Beam C., et al. “GAD vaccine reduces insulin loss in recently diagnosed Type 1 diabetes: Findings from a Bayesian meta-analysis”. Diabetologia 60 (2016): 43-49.
  60. Orban T., et al. “Autoantigen –specific regulatory Tcells induced in patients with type 1 diabetes mellitus by insulin B chain immunotherapy”. Journal of Autoimmunity 34 (2010): 408-415.
  61. Sosenko JM., et al. “The development and utility of a novel scale that quantifies the glycaemic progression towards type 1 diabetes over 6 mths”. Diabetes Care 38 (2015): 940-942.
  62. Sosenko JM., et al. “A new approach for diagnosing type 1 diabetes in autoantibody –positive individuals based on prediction and natural history”. Diabetes Care 38 (2015): 271-276.
  63. Krischer JP. “The use of intermediate endpoints in the design of type 1 diabetes prevention trials”. Diabetologia 56 (2013): 1919-1924.
  64. Wherett DK., et al. “Antigen –based therapy with glutamic acid decarboxylase(GAD) vaccine in patients with recent onset type 1 diabetes mellitus: A randomised double blind trial”. Lancet 378 (2011): 319-327.
  65. Esensten JH., et al. “CD28 Costimulation: From Mechanism to therapy”. Immunity 44.5 (2016): 973-988.
  66. Issazadeh-Navikas S., et al. “Influences of dietary components on regulatory T cells”. Molecular Medicine 18 (2012): 95-110.
  67. Gutierrez S., et al. “Effects of omega-3 fatty acids on immune cells”. International Journal of Molecular Sciences 20 (2019): E5029.
Citation: Kulvinder Kochar Kaur., et al. “Path Directed towards a Stage when we almost Cure Type1 Diabetes Mellitus (T1dm) after a Century of Insulin Advent". EC Nutrition 4.6 (2020): 37-46.

PubMed Indexed Article


EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005


EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777


EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347


EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478


EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253


EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033


EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992


EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505


EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793


EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211


EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047


EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560


EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318


EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819


EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840


EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344


EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476


EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658


EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489


EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278


EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108


EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571


EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333


EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883


EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001


EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937


EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723


EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726


EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603


EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646


EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616


EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290


EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226


EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812


EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268


News and Events


September Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the September issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for Upcoming Issue

ECronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before October 06, 2022.

Certificate of Publication

ECronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

ECronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.