Thanks, Josephine! In all honesty it is just a summary of all the things I have learned here in this great community.
I was vitamin D deficient. And I had just received my first ever flu shot 2 months before I was diagnosed. To me, the flu shot was the trigger
Yes, it is, Shawnmarie, but that doesn't mean it's causally related.
Oops, yes, I guess he did. Just shows how much my brain glazes over science!
There are apparently a number of genetic traits that pre-dispose people to autoimmune diseases like T1DM.
Here is a study of families with multiple autoimmune diseases that were studied to determine the genetics.
Several interesting things about this study:
Most autoimmune disease are far more common in women than men (80-90% are women), EXCEPT T1D, which is almost equal men and women.
T1D and Thyroid autoimmune diseases (AITD) i.e things like Hashimoto's and Grave's
are both associated with the HLA-D3 gene. T1D is also associated with HLA-D4.
Another genetic variation PTPN22 is associated with both T1D and Hashimoto's
Autoimmune disorders constitute a diverse group of phenotypes with overlapping features and a tendency toward familial aggregation. It is likely that common underlying genes are involved in these disorders. Until very recently, no specific alleles—aside from a few common human leukocyte antigen class II genes—had been identified that clearly associate with multiple different autoimmune diseases. In this study, we describe a unique collection of 265 multiplex families assembled by the Multiple Autoimmune Disease Genetics Consortium (MADGC). At least two of nine “core” autoimmune diseases are present in each of these families. These core diseases include rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), multiple sclerosis (MS), autoimmune thyroid disease (Hashimoto thyroiditis or Graves disease), juvenile RA, inflammatory bowel disease (Crohn disease or ulcerative colitis), psoriasis, and primary Sjögren syndrome. We report that a recently described functional single-nucleotide polymorphism (rs2476601, encoding R620W) in the intracellular tyrosine phosphatase (PTPN22) confers risk of four separate autoimmune phenotypes in these families: T1D, RA, SLE, and Hashimoto thyroiditis. MS did not show association with the PTPN22 risk allele. These findings suggest a common underlying etiologic pathway for some, but not all, autoimmune disorders, and they suggest that MS may have a pathogenesis that is distinct from RA, SLE, and T1D. DNA and clinical data for the MADGC families are available to the scientific community; these data will provide a valuable resource for the dissection of the complex genetic factors that underlie the various autoimmune phenotypes.
Another interesting link is here, a summary resource on diabetes genetics:
Key points of the genetics of type 1 diabetes
· Type 1 diabetes is caused by T-cell mediated pancreatic beta-cell destruction;
· Many type 1 diabetes genes may be shared by other T-cell mediated autoimmune diseases;
· The major genetic risk of type 1 diabetes is from the HLA genes, which accounts for ~50% total risk;
· The type 1 diabetes specific genetic effect is from the INS VNTR, which regulates the insulin ectopic expression in thymus and induces central immune tolerance. The protective allele is the minor allele in European population, and doesn’t exist in East Asian populations.
There is a long list of genes on this page associated with T1D , the top ones including the HLA genes mentioned above, and the gene that codes for insulin (INS).
A combination of these genetic susceptibilities along with some environmental trigger is believed to set off the autoimmune process.
This is why your endo. may test for other autoimmune diseases if you have T1D.
As always, thanks for a fact-filled reply.
From a personal anecdotal perspective, I am surprised to hear about Vitamin D deficits as a contributor. My exposure to sunlight and consumption of milk w/Vitamin D added was good to high.
Also, in the FWIW category, with the exception of asthma, there are essentially no known autoimmune issues in my family.
I had the flu just prior to diagnosis, that is definately what I believe set it off in me. There is no family history for me. I'm the ONLY insulin dependent diabetic. I had a great aunt much later in life diagnosed as a type 2 but that is it.
Hashimoto's is actually hyperthyroid and usually diagnosed after the storm when a patient is hypo. In my case, I was diagnosed during the storm and started on meds for hyperthyroid.. You have to rememeber 20 yrs ago, there probably wasn't as strong a correlation. And the starnge part was my Endo says that I should have had both closer together NOT 24yrs apart..LOL
I think it already has been covered, but when I meant was : "what was the even tor virus that triggered your T1"
There is no history of any type of Auto immune disease and not even T2 diabetes in my family. I am thinking that it CAN inherited but perhaps it can also just be a mutation that occurs randomly.
As I understand it, generally speaking the immune system is threatened by something and then it over reacts and attacks the bets cells because it misinterprets the self vs nonself markers.
I really had not expected so much insight, I was just thinking I would get a lot of different proposed causes.
I like seeing what people think on here, there are a lot of educated people on this site.
Replying to myself: I put "hypothyroid" re my graves disease when I meant to say hyperthyroid. Though just to confuse the issue, without the Synthroid I now take I would be hypo because my thyroid was destroyed by radiation because it couldn't be controlled.
Ah! I didn't see that.
I cannot really point to any infection that happened anytime near the diagnosis. They say the autoimmune destruction has been going on for some time before so many beta cells are destroyed that it finally causes control to fall apart and you get symptoms...how long that takes and therefore how far back the trigger can be I do not know.
I am the only T1 among my known relatives, though I have a cousin who had Grave's disease and my mom and sister have had thyroid issues, though never proven to be autoimmune related.
About 9 years before I was dx'ed w/D, I had Hepatitis. At that time they weren't able to distinguish between the various types of Hepatitis. I think the Hepatitis virus stayed latent in my pancreas for those 9 years until I was Dx'ed with D. That is just my theory. It can't be proven or not.
I had strep throat for over 3 months before the Diabetes finally kicked in.
I like to tell my mom it's because she smoked while she was pregnant with me. I know, it's mean....
Anyways, I was Dx'd with Hashimoto's hypothyroidism about 4 or 5 months before I was dx'd with T1. Endo at the time said a virus triggered the autoimmune response, but did not guess/investigate what it was. I had a bit of a high BG reading (180s) at a health fair about 10 months before dx'd, but never had a follow up appointment and brushed it off. My guess is that the beta cell destruction began at least a year before I became symptomatic.
Strep is a bacterial . I have never heard of that being a trigger, but then I have not heard of all these other viruses as possible triggers either.
It think it just shows how much we do not know.
I still had active virus in my system when I was diagnosed in 1989. I was also still sick from it when I was hospitalized with a fasting glucose of 600+.
I remember still coughing and being congested for a month after.
My doctors told me that they check for the most common viruses because that makes the diagnosis easier. This way they don't have to consider other reasons for high sugars like cancer or benign tumors and blocked ducts, pancreatitis. etc,
After my viral tests came back is when I got my diagniosis
Good post Holger, I thought though that the original cause of the T cell attack was in response to a protein produced when we had a virus we were trying to overcome, I remember reading that somewhere? I recently gave blood at the Faustman lab and the new person in charge of that there, Sophie, told me that I have been fighting this off my whole life most likely but somehow succumbed to it now rather than earlier in life.
I guess we can never know what caused this at this point but hopefully research will figure it out and more importantly a cure. I do think it is good to question it and think about it because this can help lead to a cure and better treatment of course.
I was told I had a virus and that this caused the autoimmune reaction. I ended up testing positive for gad 96 I think and that confirmed the autoimmune reaction common in lada. Only six months before I went into a crisis I had a normal bg of 106 non fasting. I did have a virus right around that time and I went to my doc who ran some blood work for, yes, autoimmune conditions, but not for D unfortunately or maybe I would have avoided everything else that happened. My potassium and co2 were already low then too, so that should have been a warning sign to do further testing.
The virus I had was sort of like a cold, swollen glands, my eyes were red and swollen, I had a low fever and aches/pains. I took a homeopathic remedy, slept a lot, took pain killers and ate home made cookies with tons of sugar- this seemed to do the trick.
Whether this virus caused my D or caused me to finally succumb to an ongoing T cell attack I may never know. There were many other factors that could have played a role: injuries in a car accident, emotional stress and hormonal changes. I believe these all lowered my immune response. I also think taking elavil for 5 years for chronic pain may have played a role too. My grandfather had thyroid/graves disease and was on meds for the last 40 years of his life. I don't know of anyone else in my family who has had an autoimmune condition, but there could be others.
As a child I had scarlet fever twice.
At the time of my diagnosis my doc also told me I was low in vitamin D- I have started higher doses of that to see if it helps at all with this and for bone loss etc.
actually I think it was gad 65? I always get that confused... and I'm wondering if that is related to a specific virus?
I just found this article....
GAD65 is thought to be a key autoantigen in the diabetogenic process. Early studies investigating the role of GAD65 in animal models found that GAD-specific humoral and cellular responses were directly temporally correlated with the first detectable responses to islet extracts and to the onset of insulitis in the nonobese diabetic (NOD) mouse (71,72). In addition, neonatal tolerization to GAD65 was shown to delay, and in some cases prevent, the development of diabetes in these mice (71,72,73). One proposed mechanism for GAD’s role in the pathogenesis of type 1 DM is that of molecular mimicry. Viral infections are postulated to be environmental triggers for type 1 DM, and anti-GAD reactivity may be the result of a misdirected immunologic attack against viral proteins that contain a small segment of amino acid sequence similarity to GAD. The coxsackie B4–2C protein and the mycobacterial heat shock protein 60 (HSP60) have both been identified as possible initiators of a cross-reactive immunologic response (74,75,76,77); however, the pathogenic relevance of this association has been debated (78,79).
An exciting new focus of research is the investigation of the qualitative role exerted by antibodies, which have been shown to influence the spectrum of peptides presented to T cells in the context of MHC. It is hypothesized that this process of antibody-mediated antigen internalization alters postendocytic transport and processing events, resulting in the presentation of different T-cell epitopes and potentially unmasking “cryptic” self-determinants, thus manipulating the T-cell response (reviewed in reference 225). In the case of type 1 diabetes, a particular GAD65 antibody specificity present exclusively in prediabetic patients, not in GAD65 antibody positive nondiabetic patients with other autoimmune diseases or in GAD65 antibody-positive nondiabetic controls, may therefore contribute to the initiation or perpetuation of the autoimmune process by altering the spectrum of T-cell determinants expressed by APCs and thus shifting the focus of the T-cell response.
Initial studies exploring this issue of an antibody-mediated influence on the epitope specificity of antigen presentation were conducted in model systems using monoclonal antibodies to classic antigens, such as tetanus toxoid (226,227). More recently, investigators have demonstrated that disease-associated autoantibodies can affect the processing of particular T-cell epitopes. Dai et al. demonstrated that thyroglobulin-specific monoclonal antibodies were able to either enhance or suppress the presentation of a nondominant, disease-associated T-cell epitope, depending on the epitope specificity of the antibody (228). Jaume et al. demonstrated that GAD65-specific B-cell lines modulate the spectrum of T-cell epitopes presented, again depending on the epitope specificity of the monoclonal antibody expressed on the cell’s surface (229). Thus, depending on the presence or absence of autoantibodies, the presentation of an antigen or antigen–antibody complex may affect the generation of a pathogenic T-cell response either positively or negatively. By manipulating this pathway, it may be possible to alter the course of chronic anti–β-cell destruction and the development of type 1 DM.
The past decade has seen major advances in our understanding of the pathogenesis of type 1 DM, with the identification and characterization of the major autoantigens against which the immune system is targeted in this disease process. These autoantigens were isolated and identified using autoantibodies generated by the aberrant immune response and found specifically in the sera of patients with type 1 DM. These markers of autoimmunity are also found in the serum of prediabetic subjects and provide an important tool for screening individuals at high risk and predicting their likelihood for developing type 1 DM. In addition, measurement of autoantibodies as well as genetic markers (HLA) can be used in combination to predict which individuals from the general population are likely to develop type 1 DM. As the predictive ability has improved, it has become possible to enroll prediabetic subjects in trials aimed at preventing the onset of type 1 DM. Aside from their important role as predictive markers, the type 1 DM–related autoantibodies also may play a functional role in the autoimmune disease
process, and further study of these immune markers may help us to better understand the disease pathogenesis.