Helminthic therapy and type 2 diabetes (T2D)

    From Helminthic Therapy wiki

    For type 1 diabetes, see Helminthic therapy and type 1 diabetes (T1D).

    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 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:

    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. [1]

    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. [2] [3] [4] [5] [6] Some of these studies found that the removal of 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. [7] [8]

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    Some...antiparasitic drugs might induce diabetes, whereas helminth infections appear to afford some protection against future diabetes. [9]
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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.[10]
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    Participants with previous schistosome infection had... a lower prevalence of diabetes and metabolic syndrome compared with the uninfected, contemporaneous controls. [11]
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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. [12]
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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. [13]
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    Thus helminth infections alleviate and anthelmintic therapy partially restores the plasma cytokine and chemokine levels in helminth-diabetes co-morbidity. Our data therefore offer a plausible biological mechanism for the protective effect of helminth infections against T2DM. [14]
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    In this paper, we provide a comprehensive review of intestinal helminths' protective effects against T2D. [15]

    A proof-of-concept human clinical trial is currently underway on the safety and usefulness of the human hookworm for patients with metabolic syndrome. [16]

    Type 2 diabetes and the immune system[edit | edit source]

    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 [17] Helminths are known immunomodulators, and there is evidence that they affect the immune system in a way that can help T2D [18] [19] [20] [21]

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    Helminth-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 parasite-induced immunoregulatory mechanisms might contribute to the development of new therapies for inflammatory diseases, including type 2 diabetes. [22]
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    Helminths and certain protozoan parasites 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, helminths may play a protective role against MetS disease. [23]

    There is also growing evidence to suggest that type 2 diabetes involves inflammation, [24] [25] and inflammation may be the reason why high blood sugar levels damage blood vessels in people with diabetes. [26] It’s been known for more than a decade that helminths are effective against inflammation [27] [28] [29] [30] [31]. 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. [32]

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

    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. [33] [34] [35] [36] [37] [38] [39] [40]

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    Parasitic nematode infection has both preventive and therapeutic effects against the development of obesity and associated features of metabolic dysfunction in mice. [41]
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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. [42]

    Studies on whether helminths may be an effective treatment, as well as an effective preventative measure, have also shown promise.

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    ...nematode 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. [43]
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    We demonstrate a beneficial effect of helminth infection on the systemic inflammatory milieu, intestinal dysbiosis and metabolic endotoxemia, that is highly characteristic of T2DM. [44]
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    The present study suggests that experimental infection with low hookworm doses is safe and is associated with improvements in glucose homoeostasis in people with Metabolic Syndrome and at risk of type 2 diabetes mellitus. [45]

    Scientific papers on helminths and T2D[edit | edit source]

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    These findings suggest that helminthic therapy holds the potential to become a revolutionary approach in the field of DM.
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    A growing body of evidence indicates that certain helminthic infections can enhance insulin sensitivity by modulating host immune responses and suppressing chronic inflammation, offering promise for the treatment of DM... This therapy holds the potential not only to reduce the global healthcare burden of DM but also to provide new treatment opportunities for both healthcare providers and patients.
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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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    Our data suggest that Strongyloides stercoralis infection could play a beneficial role by limiting or delaying T2DM-related vascular complications.
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    Our findings indicate that carefully controlled therapeutic hookworm infection in humans could be a novel approach for treating metabolic syndrome and thereby preventing T2D.
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    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…
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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.
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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 epidemiological evidence for the link between 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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    This review aims to examine the literature on the effect of helminthic infections on metabolic outcomes in humans.
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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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    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 helminths in the etiology of cardio-metabolic disease.
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    ... recent literature indicates that various aspects of the Th2-associated inflammatory response contribute to metabolic homeostasis.
    This review covers the mechanisms by which helminth infection affects the occurrence of T2D and cardiovascular disease.
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    diabetic patients had less intestinal parasites compared with the general population

    See also Helminthic therapy and cardiometabolic conditions

    More papers are listed on the Helminthic therapy research page.

    Scientific papers not directly related[edit | edit source]

    Clinical trials and observational studies for T2D[edit | edit source]

    See Helminthic therapy clinical trials: Diabetes type 2

    Media coverage[edit | edit source]

    Personal experiences[edit | edit source]

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    My blood sugar came down steadily with my first few doses of HDC, 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.)
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    I used to be classified as pre diabetic with a BG of 7.1 consistently over a decade. I have helminths now (NA and TTO) and I run 4.5 consistently. [46]Quotein.gif 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. [47]

    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

    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

    A substance capable of eliminating or destroying intestinal worms.

    a change which is a result or consequence of an action or other cause.

    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.

    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.)

    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 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 category of worms with slender, unsegmented, cylindrical bodies that include roundworms and threadworms.

    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 roundworm that causes strongyloidiasis and is known as 'pinworm' in the UK and 'threadworm' in the US. Infection with S. stercoralis can be fatal.

    The species of human hookworm used in helminthic therapy. Its microscopic larvae are applied periodically to the skin.

    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.)

    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

    the ova (eggs) of the human whipworm, Trichuris trichiura

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