Helminthic therapy and type 1 diabetes (T1D)

    From Helminthic Therapy wiki

    For type 2 diabetes, see Helminthic therapy and type 2 diabetes (T2D).

    NB. This page is concerned with one of the common insulin disorders known as diabetes mellitus and characterized by sustained high blood sugar levels. It is not to be confused with the hyper-production disorder, diabetes insipidus.

    See also Helminthic therapy and diabetes

    Introduction[edit | edit source]

    Type 1 diabetes (T1D) is an autoimmune disorder in which the immune system attacks and destroys insulin-producing beta cells in the pancreas. Once these cells are destroyed, the body is unable to produce insulin, which regulates blood glucose levels. A World Health Organization study found a significant difference in prevalence around the world:

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    A greater than 350-fold difference in the incidence of T1D among the 100 populations worldwide was reported with age-adjusted incidences ranging from a low of 0.1/100,000 per year in China and Venezuela to a high of 36.5/100,000 in Finland and 36.8/100,000 per year in Sardinia. The lowest incidence (<1/100,000 per year) was reported in the populations from China and South America and the highest incidence (>20/100,000 per year) was reported in Sardinia, Finland, Sweden, Norway, Portugal, the UK, Canada, and New Zealand. [1]

    A 25-year study found that the rate of type 1 diabetes in Europe is increasing by more than 3 percent per year [2], and a recent study by the US Centers for Disease control found increasing rates of both type 1 and type 2 diabetes in young US citizens. [3] The World Health Organization has found that diabetes is becoming more prevalent in middle- and low-income countries. [4]

    Many have hypothesized that the differential rates, as well as the current increase in middle- and low-income countries, may be related to industrialization and the medical and hygienic practices that come with it. [5]

    Prevention and treatment of T1D[edit | edit source]

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    Abundant evidence indicates that helminths and their by-products can exert immunomodulatory effects that prevent or delay the onset of T1D.… In the future, helminth-derived supplements may be included as part of a modern balanced diet. [6]

    There is evidence in both human and animal models that helminth infection is protective against the development of T1D. [7]. A study found that helminth infection "disrupt[s] the pathways leading to the Th1-mediated destruction of insulin-producing beta cells." [8] Findings like these have led some researchers to call for further study of helminth therapy as a deliberate preventative measure against the development of T1D. [9]

    Treatment is more complicated. Once the symptoms of this disease develop, the majority of insulin-producing beta cells have been lost. But there is cause for hope, as multiple approaches to regenerating these cells are being studied. It is now clear that, at least in mice, the pancreas contains cells capable of being converted into insulin-producing beta cells. This can be done at any age and the cells can be regenerated several times. [10] Encouragingly, another study found that a drug could encourage the generation of new insulin-producing beta cells in the human pancreas as well. [11] Stem cells are another promising subject of research on regenerating insulin-producing beta cells. [12] With the possibility of creating new beta cells, the combination of this regeneration with helminthic therapy to prevent further autoimmune destruction of beta cells may turn out to be a viable long-term treatment for Type 1 diabetes.

    There is also some evidence, however, that beta cells can be regenerated through immunomodulation alone.

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    New research shows promising progress in the use of anti-inflammatory cytokine for treatment of type 1 diabetes. The study reveals that administration of interleukin-35 (a protein made by immune cells) to mice with type 1 diabetes, reverses or cures the disease by maintaining a normal blood glucose level and the immune tolerance. [13]

    Another study found that increasing protective T-regulatory cells in the lymph nodes (the 'gates' of the pancreas) may help restore the production of insulin in T1D patients. [14] Helminths are capable of normalizing T-regs, but we don't yet have research that specifically confirms the regeneration of pancreatic beta cells through T-reg modulation via helminth infection.

    Research on mechanisms of prevention and treatment[edit | edit source]

    Animal models, while not a perfect way to study human health, allow us to understand the interaction of helminth immunomodulation and T1D on a detailed level. [15] [16]

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    In this study we show that soluble extracts of S. mansoni worm or egg completely prevent onset of type 1 diabetes in these mice but only if injection is started at 4 weeks of age... These effects of schistosome antigens on the innate immune system provide a mechanism for their ability to prevent type 1 diabetes in NOD mice. [17]
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    T cells from H. polygyrus (Hp)-inoculated NOD IL-4(-/-) mice to NOD mice blocked the onset of T1D. [18]
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    A significantly lower percentage of T. crassiceps-infected mice (40%) developed T1D compared to the uninfected group (100%). Insulitis was remarkably absent in T. crassiceps-infected mice, which had normal pancreatic insulin content, whereas uninfected mice showed a dramatic reduction in pancreatic insulin. [19]

    Some studies have also found that helminths may help, even after the onset of T1D.

    • One mouse model study found that helminth infection "significantly inhibits T1D... and also reduces the severity of T1D when administered late after the onset of insulitis." [20]
    • Experimentally induced type 1 diabetes is suppressed in mice during infection by the helminth, Heligmosomoides polygyrus. This is achieved by the secretion of trehalose which induces production of suppressive CD8+ Treg cells by means of alteration to the intestinal microbiota. [21]

    Scientific papers on helminths and T1D[edit | edit source]

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    By regulating the activities of islet macrophages and β-cells (and other endocrine cells), helminth parasites shape their crosstalk. This offers a unique opportunity to exploit helminths’ mechanisms for survival in their mammalian hosts to establish an environment that preserves β-cell mass and function and thus offers the potential as a cure for both T1D and T2D.
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    Abundant evidence indicates that helminths and their by-products can exert immunomodulatory effects that prevent or delay the onset of T1D.… In the future, helminth-derived supplements may be included as part of a modern balanced diet.
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    Helminth infections might protect against T1D diabetes development by disrupting the pathways leading to the Th1-mediated destruction of insulin-producing beta cells mediated by mechanisms related to the capacity of the host to mount a Th2 response to parasites, thus, decreasing the frequency of T1D
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    … methods designed to suppress excess production of pro-inflammatory cytokines may form a new approach to prevent both type 1 and type 2 diabetes mellitus.
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    In this review, we discuss studies that have provided evidence for the beneficial impact of helminth infections on T1D and T2D.
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    In this review we summarize studies that investigated parasitic helminths and helminth-derived products and their impact on both type 1 and type 2 diabetes highlighting potential protective mechanisms.
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    This review provides an overview of the findings from animal models and additionally explores the potential for translation to the clinic.
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    This review outlines basic insight into the ability of helminths to modulate the onset and progression of T1D, and frames some of the challenges that helminth-derived therapies may face in the context of clinical translation.
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    … it is highly likely that the decline of infections is one of the major explanations for the increased frequency of insulin-dependent diabetes in developed countries.
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    In this review, we summarize current findings regarding the effects of helminth infection on type 1 diabetes, tuberculosis, and asthma and discuss possible mechanisms through which helminthic parasites modulate host immunity.
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    In this review, some of the ways in which certain organisms might have influenced the onset of autoimmunity are discussed.

    More papers are listed on the Helminthic therapy research page.

    Scientific papers not directly related[edit | edit source]

    Clinical trials and observational studies for T1D[edit | edit source]

    See Helminthic therapy clinical trials: Diabetes type 1

    Media coverage[edit | edit source]

    Personal experiences[edit | edit source]

    A long story in Foods Matter about a 9-year-old child for whom the progress of his diabetes seems to have been halted, if not reversed, by being colonised with hookworms.

    Others

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    We started to notice high blood glucose (BG 250) in our 9 year-old in early Nov of 2012, and when we went to the endo on 20th of that month, we were given a 6-12 month projection for insulin dependence and had autoantibodies measured. The results came back significantly positive for GAD65 and IAA... About 2 days before our 6 month check up in mid Aug 2013 we went out for sushi and had ice cream afterwards. Post Prandial was 111. The Post Prandial should be below 180 to not be considered diabetic, but below 140 is more in the normal range. We were dumbfounded because, a while back, this PP would have been near the 160-180 mark if not higher. We were also not being as strict with diet and sleep, when we saw the endo, as it was summer, and we still need to be a kid! ;-) However, I really was thinking that the A1C would be at least 6.0, but it wasn't. It was 5.5... Currently we have 70HW on board and will be dosing with another 30 or so to get to the 100 mark. (Link expired)
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    My 9yo son now has 70 HW, as our effort to head off pre-diabetes. His labs show his Triiodothyronine (T3) has gone from 181 to 136 with the helminths… His hemoglobin was called "high" before helminths at 5.8... Now it's 5.7. (Reported at 10 months after the first inoculation.) [22]
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    I have a son who was tested positive for type 1 diabetes autoantibodies (ICA,GADA IAA,IA2A) at the age of 8 months. We have been told that he will almost certainly develop diabetes sooner or later. He had his first HW when he was 2 years old (3 years ago). Since then his B-HbA1C (glycosylated haemoglobin) has gradually come down from 5.7 to 5.0. Also two out of four autoantibodies have disappeared. [23] (For more about this case, see this and subsequent posts.)
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    I am 60+ male who developed LADA (latent auto-immune diabetes in adults - sometimes called Type 1.5) out of the blue appx 20+ years ago. It gradually evolved to becoming insulin dependent. Nov. 2014 (13 months ago), all was going pretty well until I developed flu-like symptoms… Small doses of ibuprofen kept the pain at bay, but overall health continued to deteriorate… Then came the periodic double vision and ocular aches. January 31st, I started losing vision in one eye for 10 minutes at a time… My CRP was 165 and Sed Rate was 67. Oops! Neural ophthalmologist and Rheumatology Docs put me on high dose of Prednisone (60mg) to knock out the inflammation which had localized in the fat cells behind my eyes… by June the docs could not determine what caused this inflammatory outbreak. They ruled out everything and primarily ended up with a diagnosis of auto-immune disease with inflammation of unknown origin. Put me on 20mg weekly of Methotrexate (MTX) to replace the prednisone, but there was still some residual inflammation around my eyes. Rheumatologists wanted to put me on Rituximab… Still fatigued most of the time. My primary suggested HT as another approach. I began taking HDC at end of July. After 3 doses I was feeling much better and started reducing my doses of MTX… I increased doses to 60 ova biweekly in mid-October and have stayed at that dose. I weaned off MTX and stopped it entirely in mid-Nov. My inflammation markers are back to normal (CRP is 4.4; Sed Rate is 11) and I feel better than I have in 12 months… Ophthalmologist says everything looks ok and to only call if any symptoms return… My primary and I are both pleased with how HT is going. [24]
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    Treating T1 Diabetes with hookworms in a 10 year old male. Initial dose: 10 NA in 2016. From weeks 6 to 7, my son's blood sugar levels were extremely stable never going over 6.5, which is very rare for a diabetic. He had a few hypos mainly to do with putting in too much insulin, but we got down from 22 units of insulin per day to just 10/12. Hookworms were still helping at approximately 1 year, but his colony might have died soon after that, when I gave him oregano oil. After that happened, we saw worsening of blood sugars. We reinoculated with 10 NA and his BGs got better and better again. Most importantly, they were consistent with his diet... After those first two doses, my son decided not to continue dosing because of the initial discomfort, and he didn’t dose at all for the next 4 years, after which he resumed the treatment with a dose of 20 NA, which caused no major reactions. Now, the treatment seems to work for the first couple of weeks but doesn't last... We'll continue dosing as he is ok about it now, and perhaps he needs to have smaller doses but more often? (Edited from three posts: [25] [26]] [27].)

    The reintroduction to the digestive tract of a controlled number of specially domesticated, mutualistic helminths (intestinal worms) in the form of microscopic eggs or larvae to reconstitute a depleted biome to treat or prevent chronic inflammation, autoimmune disease and other immune-related disorders, including allergy.

    An intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. Wikipedia:Helminths

    An intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. Wikipedia:Helminths

    The reintroduction to the digestive tract of a controlled number of specially domesticated, mutualistic helminths (intestinal worms) in the form of microscopic eggs or larvae to reconstitute a depleted biome to treat or prevent chronic inflammation, autoimmune disease and other immune-related disorders, including allergy.

    The reintroduction to the digestive tract of a controlled number of specially domesticated, mutualistic helminths (intestinal worms) in the form of microscopic eggs or larvae to reconstitute a depleted biome to treat or prevent chronic inflammation, autoimmune disease and other immune-related disorders, including allergy.

    An intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. Wikipedia:Helminths

    The specific population of microorganisms living in a certain part of the body, such as the gut. "Microbiome" refers to all the microorganisms living in and on the body, or the genome of these microorganisms. These two terms are often used interchangeably.

    An organism that lives in or on another organism (its host) and benefits at the host’s expense. (The organisms used in helminthic therapy are, strictly speaking, not parasites, but mutualists, because they have a mutually beneficial symbiotic relationship with their hosts.)

    An intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. Wikipedia:Helminths

    An organism that lives in or on another organism (its host) and benefits at the host’s expense. (The organisms used in helminthic therapy are, strictly speaking, not parasites, but mutualists, because they have a mutually beneficial symbiotic relationship with their hosts.)

    A helminth that lives in the small intestine. Necator americanus (NA) is the only hookworm species used in helminthic therapy. Its microscopic larvae are applied periodically to the skin.

    hookworm, usually referring to the human hookworm, Necator americanus

    The introduction of an infectious agent into an organism. Helminth inoculation

    C-reactive protein is an inflammation marker but is not a reliable indicator of inflammation, especially in chronic inflammatory disorders.

    helminthic therapy

    Hymenolepis diminuta cysticercoids (Hi-men-o-lep'is dim-a-nu-ta sis-ti-sur-koid) - the larval cysts of the rat tapeworm, Hymenolepis diminuta

    the human hookworm, Necator americanus

    A helminth that lives in the small intestine. Necator americanus (NA) is the only hookworm species used in helminthic therapy. Its microscopic larvae are applied periodically to the skin.

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