There are 4 main types of diabetes:
1.Type 1 or Juvenile Onset Diabetes (JOD) that starts mostly in early age and results from failure of pancreas to produce sufficient insulin to carry on the sugar to different body organs and parts. As discussed in the “Autoimmune Disorders” section, this type of diabetes is immune-mediated. Here a T-cell mediated autoimmune attack leads to the loss of beta cells of the islets of pancreas where the insulin is produced. This type of diabetes that is less than 10% of the whole diabetes, has been associated to Coxsackie B4 and most recently B1 Viruses that invade the pancreas and through “molecular mimicry”, trick the host immune system to recognize its own tissue as foreign, antigen or eiptope, and the occupying virus as the host, antibody or paratope. This deceives the immune system to produce HLA (Human Leukocyte Antigen),e.g. types DR3 and DR4 by T-cells against the pancreas to fail the production of insulin!
Coxsackievirus that belongs to a family of single strand RNA enterovirused, that also includes poliovirus and echovirus. There is estimated that there are at lease 68 human enterovirus subtypes, affecting millions of people worldwide each year, some as epidemies. These viruses often found in the respiratory secretions (e.g., saliva, sputum, or nasal mucus) and stool of an infected person and are the causes such common infections as nonspecific febrile illness, aseptic meningits and epidemic pleurodynia in children. In the United States, enteroviruses are responsible for 30 to 50 million infections in children per year and in 2007, an outbreak of coxsackievirus in China, cost the death of 22 children and affecting more than 800, leading to hospitalization of 200 children.
We stress on the above statistics not for their immediate significant common morbidities and mortalities, but for their long lasting future effects that these viruses could create in the host, e.g. causing autoimmune disorders such as diabetes mellitus type 1. These viruses as we know so far, after infecting the host cell, their genomes are translated in a cap-independent manner into single polyproteins, and subsequently by virus-encoded proteases causing their own replications and later on affecting our immune system for their generations to come.
So in the near future, hopefully the management of diabetes type 1 or juvenile onset, will be not its treatment with insulin that is already too late, but will be its prevention, by identifying, preventing the above viral infections. Or by advancing our knowledge and techniques in immunology and genetic engineering, we hopefully will be able to treat the conditions such as diabetes type 1, by reversing its genetic impact on our genome and HLA system! Vaccination or Autoantigen-specific immunotherapy with alum-formulated GAD65 (Glutamic Acid Decarboxylase) has already shown some promise to reduce the loss of beta-cell function after the clinical onset of type 1 diabetes.
2.Type 2 or Mature Onset Diabetes (MOD) that starts in adult age, mostly middle age and results from overwhelming pancreatic islet cells by overeating, specially carbohydrates, thus suppressing the production of insulin, or sensitivity of insulin to blood sugar. This type of diabetes comprises the majority of diabetic cases in more than 90% and is a result of sedentary and overeating life styles that causes obesity. This type could be insulin resistant due to the loss of sensitivity of insulin to regulate blood sugar.
3.Gestational Diabetes which could resemble and be a subtype and is some cases will evolve into type 2, happens during pregnancy in some women. This condition could be temporary, treatable and may not last after delivery.
4. Latent Autoimmune Diabetes of Adults(LADA) that is a subtype of type 1 , developing in adults and is similarly an autoimmune disorder! The immunological evidence, common in both type 1 diabetes and LADA, is demonstrated by the presence of autoantibodies against islet cell antigens in the patients’ sera. Specifically, these antigens include 65kDa glutamic acid decarboxylase (GAD65) and insulinoma-associated antigen (IA2). While type 1 diabetes shows both these autoantibodies, LADA typically demonstrates production of GAD65 autoantibodies. An association between “Cytomegalovirus” (CMV) infection and the pathogenesis of some neuroendocrine autoimmune diseases, such as LADA and Stiff Man Syndrome, through T cell crossreactivity with GAD65 has already been substantiated. Primary prevention of these autoimmune diseases therefore might be attempted by targeting the CMV virus by vaccination or tolerance-inducing induction strategies.
Dr.Mostafa Showraki, MD, FRCPC Lecturer, University of Toronto,School of Medicine,Author: “ADHD:Revisited” Book “adhdrevisited.com”/”medicinerevisited.com”
- Showraki, Mostafa. “Autoimmune Disorders”. medicinerevisited.com.
- Showraki, Mostafa. “A new look at Cancer”. medicinerevisited.com.
- Showraki, Mostafa. “A new look at infections”. medicinerevisited.com.
- Showraki, Mostafa. “Trauma and insults”. medicinerevisited.com.
- Showraki, Mostafa. “Multiple Sclerosis (MS)”. medicinerevisited.com.
- Showraki, Mostafa. “Diabetes Melitus”. medicinerevisited.com.
- Shoback, edited by David G. Gardner, Dolores (2011). Greenspan’s basic & clinical endocrinology (9th ed.). New York: McGraw-Hill Medical.
- Hawa MI, Kolb H, Schloot N, Beyan H, Paschou SA, Buzzetti R, Mauricio D, De Leiva A, Yderstraede K, Beck-Neilsen H, et al. Adult-onset autoimmune diabetes in Europe is prevalent with a broad clinical phenotype: Action LADA 7. Diabetes Care. 2013 Apr; 36(4):908-13. Epub 2012 Dec 17.
- Green J, Casabonne D, Newton R.Coxsackie B virus serology and Type 1 diabetes mellitus: a systematic review of published case-control studies. Diabet Med. 2004 Jun; 21(6):507-14.
- Roep BO, Hiemstra HS, Schloot NC, De Vries RR, Chaudhuri A, Behan PO, Drijfhout JW.Molecular mimicry in type 1 diabetes: immune cross-reactivity between islet autoantigen and human cytomegalovirus but not Coxsackie virus. Ann N Y Acad Sci. 2002 Apr; 958:163-5.
- Nguyen C, Varney MD, Harrison LC, Morahan GDefinition of high-risk type 1 diabetes HLA-DR and HLA-DQtypes using only three single nucleotide polymorphisms.Diabetes. 2013 Jun; 62(6):2135-40. Epub 2013 Feb 1.
- Rubinstein P.HLA and IDDM: facts and speculations on the disease gene and its mode of inheritance.Hum Immunol. 1991 Apr;30(4):270-7.
- MacDonald MJ, Gottschall J, Hunter JB, Winter KL.HLA-DR4 in insulin-dependent diabetic parents and their diabetic offspring: a clue to dominant inheritance.Proc Natl Acad Sci U S A. 1986 Sep; 83(18):7049-53.
- Sheehy MJ.Baillieres.T cell defined HLA epitopes and T cell receptor polymorphism in insulin dependent diabetes mellitus.
Clin Endocrinol Metab. 1991 Jun; 5(2):341-55.
3 thoughts on “Diabetes Melitus”
Howdy I am so happy I found your blog page, I really found you by accident, whileView Comment
I was looking on Google for something else, Anyhow I am here now and would just like to say many thanks for a incredible post and a
all round enjoyable blog (I also love the theme/design), I don’t have time to read
it all at the moment but I have saved it and also added in your RSS feeds, so when I have time
I will be back to read a lot more, Please do keep
up the awesome work.
Can I simply say what a relief to discover someone thatView Comment
really knows what they are discussing on the web.
You actually understand how to bring a problem to light and make it important.
More people have to check this out and understand this side of your story.
I was surprised you’re not more popular given that you
definitely have the gift.
Thankyou for helping out, good information.View Comment