Difference between revisions of "Helminthic therapy and diabetes"

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*[https://www.ncbi.nlm.nih.gov/pubmed/25368615 Priming dendritic cells for th2 polarization: lessons learned from helminths and implications for metabolic disorders.]  
 
*[https://www.ncbi.nlm.nih.gov/pubmed/25368615 Priming dendritic cells for th2 polarization: lessons learned from helminths and implications for metabolic disorders.]  
 
::{{Quote|indent}}...recent literature indicates that various aspects of the Th2-associated inflammatory response contribute to metabolic homeostasis.{{Quote|/indent}}
 
::{{Quote|indent}}...recent literature indicates that various aspects of the Th2-associated inflammatory response contribute to metabolic homeostasis.{{Quote|/indent}}
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*[https://www.ncbi.nlm.nih.gov/pubmed/31492623 Immune Regulation of Metabolic Homeostasis by Helminths and Their Molecules]
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::{{Quote|indent}}In this review we discuss how helminths, which are among the strongest natural inducers of type 2 immunity, and some of their unique immunomodulatory molecules, may contribute to the maintenance of tissue-specific and whole-body metabolic homeostasis and protection against obesity-associated meta-inflammation… Importantly, controlled human infection with Necator americanus shows promising results in terms of safety and tolerability…{{Quote|/indent}}
  
 
More recent papers are listed on the [[Helminthic therapy research | '''Helminthic therapy research''']] page, which should be searched using the terms, “diabet”, “insulin”, “glucose” and “metabolic”.
 
More recent papers are listed on the [[Helminthic therapy research | '''Helminthic therapy research''']] page, which should be searched using the terms, “diabet”, “insulin”, “glucose” and “metabolic”.

Latest revision as of 21:22, 8 September 2019

Home>Effects of helminthic therapy>Helminthic therapy and diabetes

Type 1 and Type 2 diabetes are major health issues across the globe. There is evidence that helminthic therapyThe 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 and prevent chronic inflammation, autoimmune disease and other immunological disorders including allergy. may assist with prevention and treatment of these disorders.

Type 1 diabetes

HelminthsAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths] and type 1 diabetes

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

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Abundant evidence indicates that helminthsAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths] and their by-products can exert immunomodulatory effects that prevent or delay the onset of T1D.… In the future, helminthAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths]-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 therapyThe 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 and prevent chronic inflammation, autoimmune disease and other immunological disorders including allergy. 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 therapyThe 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 and prevent chronic inflammation, autoimmune disease and other immunological disorders including allergy. 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] HelminthsAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia: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

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 helminthsAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths] may help, even after the onset of T1D:

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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]

Personal experiences

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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 HWhookworm, usually referring to the human hookworm, Necator americanus 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.” [21]
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My 9yo son now has 70 HWhookworm, usually referring to the human hookworm, Necator americanus, as our effort to head off pre-diabetes. His labs show his Triiodothyronine (T3) has gone from 181 to 136 with the helminthsAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths]… His hemoglobin was called "high" before helminthsAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths] at 5.8... Now it's 5.7. (Reported at 10 months after the first inoculationThe introduction of an infectious agent into an organism. [http://helminthictherapywiki.org/wiki/index.php/Helminth_inoculation Helminth inoculation].) [22]
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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. [23]

Also see, Helminthic therapy personal stories: Diabetes type 1.

Type 2 diabetes

HelminthsAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths] and type 2 diabetes

Type 2 diabetes (T2D) is a condition in which the body still produces insulin, but develops insulin resistance and cannot use it effectively. The pancreas will try to compensate by producing more insulin, leading to glucose accumulation in the bloodstream. T2D can lead to health complications such as kidney problems, vision problems, nerve damage, poor blood circulation, heart attack, stroke, erectile dysfunction, and slow wound healing. Risk factors for T2D are mainly age, obesity, family history, and physical inactivity, but there is significant geographical variation in prevalence that points to additional risk factors:

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As in type 1 diabetes, there is marked geographical variation, but the pattern is different. The prevalence is lowest in rural areas of developing countries, generally intermediate in developed countries, and highest in certain ethnic groups, particularly those that have adopted Western lifestyle patterns... It is likely that interactions between the environment/lifestyle and genetic factors provide the explanation for the risk of type 2 diabetes. [24]

Some explanation of this geographic variation may relate to rates of helminth infection, which a number of studies around the globe have shown to be protective against the development of T2D. [25] [26] [27] [28] [29] Some of these studies found that the removal of helminthsAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths] from an individual appears to increase their risk of insulin resistance and T2D. This could be an important, but overlooked, contributor to the higher prevalence of T2D in industrialized nations, where helminth infections are much lower. [30] [31]

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Some...antiparasitic drugs might induce diabetes, whereas helminth infections appear to afford some protection against future diabetes. [32]
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Helminth infections... may be protective against the development of diabetes, and this finding opens up new territory for discovery of novel therapeutics for the prevention and treatment of diabetes.[33]
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Participants with previous schistosome infection had... a lower prevalence of diabetes and metabolic syndrome compared with the uninfected, contemporaneous controls. [34]
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We found previous schistosome infection (PSI) significantly correlated with lower prevalences of metabolic syndrome and its components, including central obesity, hypertriglyceridemia and low high-density lipoprotein cholesterol, which indicates that the potential long-term effects of PSI may reduce the risk of metabolic syndrome. [35]
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Low fasting blood sugar and reduced prevalence of dyslipidemia in S. mansoni egg positive participants might suggest inverse association of S. mansoni infection and development of metabolic syndromes. [36]

A proof-of-concept human clinical trial is currently underway on the safety and usefulness of the human hookwormA 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. for patients with metabolic syndrome. [37]

Type 2 diabetes and the immune system

It is becoming more apparent that the immune system is involved in T2D, as researchers find that experimental immunomodulation has an effect on this condition [38] HelminthsAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths] are known immunomodulators, and there is evidence that they affect the immune system in a way that can help T2D [39] [40] [41] [42]

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HelminthAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths]-induced type 2 cytokines increase the number of regulatory T cells and alternatively activated macrophages, resulting in modulation of the host-immune system. Studies on these parasiteAn 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.)-induced immunoregulatory mechanisms might contribute to the development of new therapies for inflammatory diseases, including type 2 diabetes. [43]
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HelminthsAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths] and certain protozoan parasitesAn 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.) are able to manipulate the host immune response towards a TH2 immune phenotype that is beneficial for their survival, and there is emerging data that there is an inverse correlation between the incidence of MetS (metabolic syndrome) and helminth infections, suggesting that, as with autoimmune and allergic diseases, helminthsAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths] may play a protective role against MetS disease. [44]

There is also growing evidence to suggest that type 2 diabetes involves inflammation, [45] [46] and inflammation may be the reason why high blood sugar levels damage blood vessels in people with diabetes. [47] It’s been known for more than a decade that helminthsAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths] are effective against inflammation [48] [49] [50] [51] [52]. A 2017 study found that:

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...helminth infections... can modulate IR is by inducing a chronic, nonspecific, low-grade, immune suppression mediated by modified T-helper 2 (Th2) response (induction of both Th2 and regulatory T cells) which can in turn suppress the proinflammatory responses and promote insulin sensitivity. [53]

Research on mechanisms of prevention and treatment

Controlled studies on animal models have helped scientists understand how helminth infection can prevent T2D through immunomodulation, gut biome alteration, fatty acid metabolism, and other mechanisms. [54] [55] [56] [57] [58] [59] [60]

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ParasiticAn 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.) nematodeA category of worms with slender, unsegmented, cylindrical bodies that include roundworms and threadworms. infection has both preventive and therapeutic effects against the development of obesity and associated features of metabolic dysfunction in mice. [61]
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Recent studies in mice describe how type 2 immune cells, traditionally associated with helminth infection, maintain adipose tissue homeostasis and promote adipose tissue beiging, protecting against obesity and metabolic dysfunction. [62]

Studies on whether helminthsAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths] may be an effective treatment, as well as an effective preventative measure, have also shown promise.

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...nematodeA category of worms with slender, unsegmented, cylindrical bodies that include roundworms and threadworms. infection appears to provide an effective option for the treatment of T2D by improving inflammatory status through restoration of the cytokine imbalance, inhibition of glucose absorption from the small intestine and decline of excess fat accumulation in the liver. [63]

Personal experiences

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My blood sugar came down steadily with my first few doses of HDCHymenolepis diminuta cysticercoids (Hi-men-o-lep'is dim-a-nu-ta sis-ti-sur-koid) - the larval cysts of the rat tapeworm, Hymenolepis diminuta, until I was getting readings of 70 (close to perilously low!). Then it normalized to 90-100 range (excellent even for non-diabetics) when dosing with 30 every 2 weeks. When a shipment went astray, my blood sugar crept up to diabetic levels again. The replacement dose arrived 2 weeks late, but brought quick relief, and five days after taking this dose, I was normal again. My blood sugar readings went down each day: first 130 (solidly diabetic), next day 122 (borderline), then 110 (fair), 103 (good) until today 100, NORMAL! (Received via email.)

Roughly 10-15% of type 2 diabetes cases may be an autoimmune disorder known as latent autoimmune diabetes in adults (LADA), also known as "type 1.5" diabetes. [64] A helminthic therapyThe 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 and prevent chronic inflammation, autoimmune disease and other immunological disorders including allergy. user with LADA shared his experience:

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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 CRPC-reactive protein is an inflammation marker but is not a reliable indicator of inflammation, especially in chronic inflammatory disorders. 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 HThelminthic therapy as another approach. I began taking HDCHymenolepis diminuta cysticercoids (Hi-men-o-lep'is dim-a-nu-ta sis-ti-sur-koid) - the larval cysts of the rat tapeworm, Hymenolepis diminuta 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 (CRPC-reactive protein is an inflammation marker but is not a reliable indicator of inflammation, especially in chronic inflammatory disorders. 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 HThelminthic therapy is going. [65]

Also see, Helminthic therapy personal stories: Diabetes type 2.

Further reading

The following papers are reviews of the scientific literature, and may be helpful for those who want to learn more about this topic:

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Herein, we provide a comprehensive review of the effects and mechanisms underlying protection against T1D by helminthsAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths].
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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 parasiticAn 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.) helminthsAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths] and helminthAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths]-derived products and their impact on both type 1 and type 2 diabetes highlighting potential protective mechanisms.
This review covers the mechanisms by which helminth infection affects the occurrence of T2D and cardiovascular disease.
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This review seeks to give an overview of the current international diabetes burden, the evidence for interactions between diabetes and infection, immune mechanisms for the interaction, and potential interventions to tackle the dual burden of diabetes and infection.
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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 helminthsAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths] to modulate the onset and progression of T1D, and frames some of the challenges that helminthAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths]-derived therapies may face in the context of clinical translation.
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In this review, some of the ways in which certain organisms might have influenced the onset of autoimmunity are discussed.
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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 parasitesAn 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.) modulate host immunity.
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In this review, we survey existing studies in the non-human animal and human literature, highlight unresolved questions and suggest future directions to explore the role of helminthsAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths] in the etiology of cardio-metabolic disease.
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In this review, we summarize epidemiological evidence for the link between helminthsAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths] and T2D and discuss the potential mechanisms, based on findings from experimental studies as well as the limited number of studies in humans.
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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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This review aims to examine the literature on the effect of helminthic infections on metabolic outcomes in humans.
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...recent literature indicates that various aspects of the Th2-associated inflammatory response contribute to metabolic homeostasis.
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In this review we discuss how helminthsAn intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. [https://en.wikipedia.org/wiki/Helminths Wikipedia:Helminths], which are among the strongest natural inducers of type 2 immunity, and some of their unique immunomodulatory molecules, may contribute to the maintenance of tissue-specific and whole-body metabolic homeostasis and protection against obesity-associated meta-inflammation… Importantly, controlled human infection with Necator americanusThe species of human hookworm used in helminthic therapy. Its microscopic larvae are applied periodically to the skin. shows promising results in terms of safety and tolerability…

More recent papers are listed on the Helminthic therapy research page, which should be searched using the terms, “diabet”, “insulin”, “glucose” and “metabolic”.

Other information

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