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    Celiac Disease and Type 1 Diabetes Share Common Genes


    Jefferson Adams

    Celiac.com 12/12/2008 - For some time now scientists have been working to better understand the connection between celiac disease and diabetes.


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    About 10% of children and 2% of adults with Type 1 diabetes also have celiac disease, as compared to just 1% of the general population. Moreover, celiac disease and diabetes are known to have a common genetic susceptibility locus in the HLA system, specifically, HLA class II alleles on chromosome six.

    The primary susceptibility genes for type-1 diabetes are HLA-DQB1 and HLA-DRB1, but they act in combination with non-immune system genes as well as environmental factors that are still undiscovered. Celiac disease also has a major susceptibility gene in the HLA system — HLA-DQB1 — as well as locations outside the HLA complex.

    Recently, a research team led by John Todd, Ph.D., of the University of Cambridge, set out to better understand the connection between the two diseases, and to determine if they shared any non-HLA regions. They discovered another seven regions outside of the HLA system that are tied to both celiac disease and diabetes.

    One of those regions is the 32-base pair insertion-deletion variant on chromosome three that leads to a non-functional CCR5 receptor on T cells. People who carry both pairs of these genes enjoy some protection against HIV infection, and its role in both celiac disease and diabetes indicates that lymphocytes are a key factor in both diseases. Carriers of these genes also face a greater risk of developing either celiac disease or diabetes, or both conditions in their lifetimes.

    In genome-wide association studies, eight loci outside the HLA system have been associated with celiac disease. Similarly, 15 non-HLA loci have been linked with Type 1 diabetes.

    Dr. Todd and colleagues genotyped single nucleotide polymorphisms (SNPs)—single letter variations in the genetic code—in the eight celiac loci and in the 15 diabetes loci.

    They then screened DNA samples from 9,339 control subjects, 2,560 subjects with celiac disease, and 8,064 subjects with diabetes. They also tested the diabetic children, along with both biological parents in 2,828 families. The overall statistical significance was P<1.00×10−4.

    At the same level of significance, three celiac disease locations—RGS1 on chromosome one, IL18RAP on chromosome two, and TAGAP on chromosome six—were also associated with Type 1 diabetes. The minor alleles of IL18RAP and TAGAP were associated with some protection from in Type 1 diabetes, but were associated with susceptibility in celiac disease.

    The CCR5 variant on chromosome three was newly tied to Type 1 diabetes (at P=1.81×10−8) and was also tied with celiac disease, together with PTPN2 on chromosome 18 and CTLA4 on chromosome two. Counting SH2B3 on chromosome 12, which already known to be a shared locus—the number of non-HLA areas strongly tied to both celiac disease and diabetes stands at seven.

    Dr. Todd and colleagues said it's possible that a common genetic background with respect to autoimmunity and inflammation—combined with disease-specific variation at HLA and non-HLA genes as well as non-genetic factors -- might lead to different clinical outcomes. It is possible that dietary exposure to gluten in the form of cereal grains might play a role in the pathogenesis of Type 1 diabetes.

    These findings offer support a growing scientific view that many common diseases share genetic risk factors, and indicate that celiac and diabetes may in fact have common biological causes, and that the two disorders may be more closely linked than previously understood.

    More research is needed to determine which shared risk factors might reveal previously unexpected biologic connections between diseases.

    New England Journal of Medicine 2008; 359: 2767-77, 2837-2838

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    Guest Debbie Johnson

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    Yes! I'm so happy to see the research that has been done on this topic. I've heard from some people who've used my cookbook that there is a link between celiac disease and diabetes, and that some diabetics have improved greatly, even getting off insulin at times, with a gluten-free diet! Of course they still have to eat low-glycemic and that's a challenge with gluten-free.

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    Jefferson Adams
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    Jefferson Adams
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    Source: Gastro 2009, UEGW/WCOG; London, UK: 21–25 November



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    Source:
    ENDO 2010: The Endocrine Society 92nd Annual Meeting: Abstract P2-111. Presented June 20, 1020.

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    Dr. Ron Hoggan, Ed.D.
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    There are many reports in such journals connecting brain and neurological ailments with gluten, so it is not much of a stretch, on that basis alone, to suspect that stuttering may be a symptom of the gluten syndrome. Rodney Ford has even characterized celiac disease as an ailment that may begin through gluten-induced neurological damage (13) and Marios Hadjivassiliou and his group of neurologists and neurological investigators have devoted considerable time and effort to research that reveals gluten as an important factor in a majority of neurological diseases of unknown origin (14) which, as I have pointed out previously, includes most neurological ailments.
    My own experience with stuttering is limited. I stuttered as a child when I became nervous, upset, or self-conscious. Although I have been gluten free for many years, I haven’t noticed any impact on my inclination to stutter when upset. I don’t know if they are related, but I have also had challenges with speaking when distressed and I have noticed a substantial improvement in this area since removing gluten from my diet. Nonetheless, I have long wondered if there is a connection between gluten consumption and stuttering. Having done the research for this article, I would now encourage stutterers to try a gluten free diet for six months to see if it will reduce or eliminate their stutter. Meanwhile, I hope that some investigator out there will research this matter, publish her findings, and start the ball rolling toward getting some definitive answers to this question.
    Sources:
    1. Toft M, Dietrichs E. Aggravated stuttering following subthalamic deep brain stimulation in Parkinson’s disease--two cases. BMC Neurol. 2011 Apr 8;11:44.
    2. Tani T, Sakai Y. Stuttering after right cerebellar infarction: a case study. J Fluency Disord. 2010 Jun;35(2):141-5. Epub 2010 Mar 15.
    3. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    4. Jäncke L, Hänggi J, Steinmetz H. Morphological brain differences between adult stutterers and non-stutterers. BMC Neurol. 2004 Dec 10;4(1):23.
    5. Kell CA, Neumann K, von Kriegstein K, Posenenske C, von Gudenberg AW, Euler H, Giraud AL. How the brain repairs stuttering. Brain. 2009 Oct;132(Pt 10):2747-60. Epub 2009 Aug 26.
    6. Galantucci S, Tartaglia MC, Wilson SM, Henry ML, Filippi M, Agosta F, Dronkers NF, Henry RG, Ogar JM, Miller BL, Gorno-Tempini ML. White matter damage in primary progressive aphasias: a diffusion tensor tractography study. Brain. 2011 Jun 11.
    7. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    8. [No authors listed] Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 43-1988. A 52-year-old man with persistent watery diarrhea and aphasia. N Engl J Med. 1988 Oct 27;319(17):1139-48
    9. Molteni N, Bardella MT, Baldassarri AR, Bianchi PA. Celiac disease associated with epilepsy and intracranial calcifications: report of two patients. Am J Gastroenterol. 1988 Sep;83(9):992-4.
    10. http://ezinearticles.com/?Food-Allergy-and-Stuttering-Link&id=1235725 
    11. http://www.craig.copperleife.com/health/stuttering_allergies.htm 
    12. https://www.celiac.com/forums/topic/73362-any-help-is-appreciated/
    13. Ford RP. The gluten syndrome: a neurological disease. Med Hypotheses. 2009 Sep;73(3):438-40. Epub 2009 Apr 29.
    14. Hadjivassiliou M, Gibson A, Davies-Jones GA, Lobo AJ, Stephenson TJ, Milford-Ward A. Does cryptic gluten sensitivity play a part in neurological illness? Lancet. 1996 Feb 10;347(8998):369-71.

    Jefferson Adams
    Celiac.com 06/14/2018 - Refractory celiac disease type II (RCDII) is a rare complication of celiac disease that has high death rates. To diagnose RCDII, doctors identify a clonal population of phenotypically aberrant intraepithelial lymphocytes (IELs). 
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    Source:
    Journal of Clinical Pathologyhttp://dx.doi.org/10.1136/jclinpath-2018-205023