The Intriguing Connection Between Toxoplasmosis and Diabetes

Contrary to popular belief, toxoplasmosis is not transmitted solely by contact with cats. According to the FDA, about 50% of toxoplasmosis infections in the U.S. each year are acquired from food, particularly meat. Interestingly, ticks are also a source of distribution of this parasite. See 2019's "Tick transmission of toxoplasmosis," 2016's "The role of ticks in transmission cycle of Toxoplasma gondii," 2020's "Molecular Detection of Toxoplasma Gondii in Haemaphysalis Ticks in Korea," 2022's "Toxoplasma gondii and Rickettsia spp. in ticks collected from migratory birds in the Republic of Korea," and others.

I didn't go to the doctor really at all before my Type 1 diagnosis. Two times in my life, I have driven to Danbury Hospital in Connecticut: One when I was in DKA in 2018, and (I'm looking in my records and I can't find the date) I believe in 2011 for when I was diagnosed with a severe tick-borne Rickettsial disease known as Ehrlichiosis. Both times in triage they asked what was wrong and I just said something along the lines of I don't know, I think I might be dying. The affliction of that tick-borne disease was when my health took a massive tailspin. I entered a consistent state of the sky falling in on me from all directions. I often recall the years prior to this as full of carefree adventure; driving to Fort De Soto beach in a convertible with Blink 182's "Violence" blasting.

According to the 2023 study Association between Toxoplasma gondii Infection and Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis: "Type 1 diabetes, an autoimmune disease characterized by damage to pancreatic insulin-producing beta cells, is associated with adverse renal, retinal, cardiovascular, and cognitive outcomes, possibly including dementia. Moreover, the protozoal parasite Toxoplasma gondii has been associated with type 1 diabetes...While our study is not designed to identify the mechanisms by which Toxoplasma gondii infection could be associated with type 1 diabetes, at least a few broad and not necessarily mutually exclusive possibilities could account for a possible positive association between type 1 diabetes and Toxoplasma gondii infection. The immunocompromised state associated with type 1 diabetes could increase Toxoplasma gondii infection rates. Neutrophil, monocyte, and T-cell dysfunction in type 1 diabetes could increase a host's chances of contracting an infection with Toxoplasma gondii, as both the innate and adaptive immune responses may be impaired in type 1 diabetes. With less neutrophil chemotaxis, the body is unable to fight off the initial infection with Toxoplasma gondii. More than 25 percent of patients with type 1 diabetes lack complement component 4 (C4), a protein found on the surface of cells that is crucial in the opsonization of pathogens. Without C4 marking the surface of a cell for phagocytosis, the parasite, in this case Toxoplasma gondii, is not neutralized, and infection is much more likely. In addition to these factors, there are several common abnormalities of the immune system before the onset of type 1 diabetes, including the depletion of memory CD4+ cells and defective natural killer cell activity, which could increase the ability of Toxoplasma gondii to infect a host. In addition to the decreased immune function associated with type 1 diabetes, another possible explanation for a possible positive association between Toxoplasma gondii infection and type 1 diabetes is that Toxoplasma gondii could induce autoimmunity against beta cells in the pancreas, thereby causing type 1 diabetes by damaging insulin secretion from beta cells...In a murine model..animals experimentally infected with Toxoplasma gondii developed necrotic lesions in their pancreas. They concluded that the death of pancreatic cells leads to the inhibition of insulin secretion and, therefore, the development of type 1 diabetes. Similarly...toxoplasmosis increases susceptibility to developing type 1 diabetes due to the ability of the parasite Toxoplasma gondii to invade and replicate inside pancreatic cells, inhibit insulin production, and increase glucose concentration. Furthermore...all mice with chronic Toxoplasma gondii infection had insulitis and inflammation of the islets of Langerhans. There was also evidence of smaller islets and a change in the number of islets in chronically infected mice, possibly related to apoptosis."

I have CBCs run regularly and have seen hematologists both in Connecticut and Florida, and my neutrophils and white blood cells in particular are always low. They were alarmingly low after DKA, so much so that I had to get a workup in oncology to dismiss the possibility of leukemia. After a great deal of effort with immune boosting regimens, it's now at a low normal number. My Immunoglobulin E (IgE) count also came up low at 3. That was the only immunoglobulin tested. Dismissively, I was told that these are immune antibodies you really don't need. I said something along the lines of "Got it, OK," while nodding, but truthfully I was dismayed and holding back tears, thinking about all the reading I did once I received the lab results a week before the appointment and how badly I just wanted some answers, some semblance of my life back. IgE is involved in fighting parasitic infections and cancers. See the 2017 paper IgE, what is it good for? ("Schistosoma mansoni, a blood fluke, infection is not cleared well in mice that are deficient in IgE"), 2023's Lancet paper Cancer is Becoming the Leading Cause of Death in Diabetes, 2020's Ultra-Low IgE: A Potential Novel Biomarker in Cancer and 2021's Insights from IgE Immune Surveillance in Allergy and Cancer for Anti-Tumour IgE Treatments ("With epidemiological findings highlighting several high-risk cancer types protected by high IgE levels, it is possible that use of IgE-based therapeutics for a range of malignant indications may offer efficacy to complement that of established IgG-class antibodies"), 2023's Relationship Between Immunoglobulin E Deficiency and Autoimmune Disease: A Paradigm of Primary Biliary Cholangitis, and the March 2023 press release out of PR Newswire: "Selagine Enters into a Collaborative Agreement with Grifols for Development and Commercialization of Immunoglobulin Eye Drops for Treating Dry Eye Disease". I was intrigued reading about the drug Dupixent (dupilumab), which causes a "profound" decrease in IgE levels in patients with certain allergic disorders. Many Dupixent patients subsequently develop severe ocular and facial reactions as a result of a proliferation of the parasitic Demodex mite. See 2024's Increased Demodex mites after dupilumab therapy in facial skin: A case report, 2020's Facial Redness in Atopic Dermatitis Patients Treated with Dupilumab: A Case Series, 2021's Demodex Folliculitis and Recent Dupilumab Administration, 2021's Rosacea Associated with Dupilumab Therapy, 2022's Clinical Characteristics and Treatment for Dupilumab-Related Ocular Complications in Atopic Dermatitis Patients, 2021's Dupilumab-associated ocular surface disease: presentation, management and long-term sequelae, 2018's Could conjunctivitis in patients with atopic dermatitis treated with dupilumab be caused by colonization with Demodex and increased interleukin-17 levels? and more.

The 2016 study Is chronic toxoplasmosis a risk factor for diabetes mellitus? A systematic review and meta-analysis of case-control studies states: "A possible association between toxoplasmosis and DM would entail significant clinical consequences, shedding light on the complicated pathogenesis of DM. Overall, the current hypothesis suggests that toxoplasmosis increases susceptibility to acquiring diabetes and, on the other hand, diabetic patients are more vulnerable to opportunistic infections such as toxoplasmosis. Subsequently, to elucidate this association, various empirical evidence have been appraised and proposed as plausible pathophysiological mechanisms, including: (1) infected white blood cells represent enhanced migratory feature, leading to the easier spread of Toxoplasma in body organs, e.g. pancreas, (2) a clinically conspicuous autoimmune response could be ignited by T. gondii infection, trending immune machinery toward autoantibody production, for instance against beta cells of Langerhans islets; (3) ...better replication of Toxoplasma occurs in insulin-producing beta cells, leading to activation of autoimmunity pathways as well as provoking the inflammation of Langerhans islets (insulitis) and ultimately developing diabetes, (4) a possibility is that T. gondii itself may invade and destroy pancreatic beta cells directly, instigating pancreatitis and more importantly, diabetes, (5) production of reactive oxygen species and nitric oxide is induced by diabetes, and these agents, as stimulant for intra-cellular pathogens, can re-activate latent cysts of parasites, again initiating acute infection; (6) given the ability of neutrophils to correctly perform phagocytosis and intra-cellular killing in progressive phase of diabetes, there may be increased responsiveness to intra-cellular pathogens such as Candida and Toxoplasma, and (7) the opsonization activity and leukocyte cytotoxicity of diabetic patients required for elimination of pathogens are considerably subsided, hence they would be more prone to opportunistic infections."

The 2023 study Seroepidemiology of Toxoplasma gondii Infection in Diabetic Patients and the Impact of Toxoplasmosis on Diabetes Associated Complications in Minia City, Egypt found: "The total seroprevalence of Toxoplasma gondii was significantly higher in diabetic patients of both types than in healthy control individuals. Recent Toxoplasma gondii infection was clearly observed in type 2 diabetic patients...There is a significant association between Toxoplasma gondii infection and diabetes; also, Toxoplasma gondii could be a potential cause of diabetes. Moreover, type 2 diabetes patients are more susceptible to acquiring Toxoplasma gondii infections, and this infection could be a risk factor for diabetes complications." Higher A1c diabetics were shown to be more susceptible than those with a lower A1c.

A study I mentioned in a previous post (The Inverse Relationship between Glucose and GABA) is 2015's Toxoplasma gondii infections alter GABAergic synapses and signaling in the central nervous system, which states: "During infections with the protozoan parasite Toxoplasma gondii, GABA is utilized as a carbon source for parasite metabolism and also to facilitate dissemination by stimulating dendritic-cell motility...taken together, these data support a model in which seizures and other neurological complications seen in Toxoplasma-infected individuals are due, at least in part, to changes in GABAergic signaling." In an interview with NeuroScience News, the authors said they "repeated the experiment many times before we believed the results." 

I typed "GAD65 diabetes" into Google Scholar recently and a very upsetting paper was on there that deeply, deeply saddened me. It's from late 2023 and titled Latent Autoimmune Diabetes in Adults and a Continuous Glucose Monitoring Device: An Unfortunate Outcome. This gentleman was only 44 and had been recently diagnosed with anti-GAD-65 antibody positive LADA or Latent Autoimmune Diabetes in Adults. This man also had a history of OCD, which is not a surprise to me at all given his anti-GAD-65 positive results. Again please read my previous post The Inverse Relationship Between Glucose and GABA. I saw a video that explained the GAD enzyme well. Without the GAD enzyme "switch", you have your foot planted on the gas with no brakes. Based on all of my medical literature reading, it feels like countless papers on this subject, it’s very easy to theorize that lack of GABA and overdrive of glutamate is the genesis of a wide span of increasingly common, debilitating mental and neurological health ailments, including OCD, panic disorder, Alzheimer's, Parkinson's, epilepsy, insomnia, schizophrenia, etc.

Back to the gentleman mentioned in this study - he was calling into his endocrinologist's office about his blood sugar numbers, but often and obsessively because of his disorder, which he was unfortunately not receiving any treatment for. I wonder what the response was on the other end. He was also experiencing panic attacks and insomnia and ended up taking his own life. It makes me tear up how badly I wish I could have been on the other end of the phone for him and helped to make him feel safe, heard and understood in some way. Because you do not truly understand it unless you are in it. It takes an exceptional amount of discipline and dedication to be a well-controlled diabetic (particularly when you get lucky enough to get the most severe, incurable kind - sort of like God directing your gondola right to the top of Rambo in Crested Butte. Welp, see ya later!). It can be stressful even when solely eating keto organic salads every day. I remember calling into endocrinology soon after coming out of the hospital and saying I felt “very weird.” When they discharged me, I still very much felt like the world was in slow motion and I would never come back to regular speed. I couldn't see very well. "Eat something!" the nurse barked at me and hung up the phone. I never called in again. Just a few studies I'd like to add. Unfortunately, clinical care in this arena lags far behind newly emerging research. In 2021's A Diagnostic Dilemma of Antiglutamic Acid Decarboxylase 65 (Anti-GAD 65) and Mycoplasma Pneumoniae Antibodies in a Girl Presenting with Acute Onset Obsessive-Compulsive Disorder the authors state: "She was also positive for anti-GAD antibodies, which are reportedly associated with reduced gamma-aminobutyric acid (GABA) transmission and can lead to seizures, increased anxiety, behavioral changes, and encephalitis...She did not respond to azithromycin despite having a 13 day course. We hypothesize that she did not have an active M. pneumoniae infection on presentation, rendering the antibiotics ineffective...She also received steroids with minimal effect...However, the dramatic response to plasmapheresis suggests that the inciting antibodies were ultimately cleared and no longer exerting their antineuronal effect. Whether this improvement was secondary to clearance of M. pneumoniae-associated antibodies or anti-GAD 65 antibodies remains unclear." Research out of University College in London in 2023 states "People with obsessive-compulsive disorder have an imbalance of brain chemicals...Scientists have suspected that this involves an imbalance between chemical messengers, or neurotransmitters, called glutamate and gaba in certain brain regions. While glutamate promotes communication between neurons, gaba reduces or inhibits neural communication (calming the central nervous system). Imbalances in these chemicals can therefore make communications more or less difficult with neural circuits in the brain - potentially leading to symptoms such as compulsions and intrusive thoughts. To study glutamate and gaba, we used a high-strength magnet (called 7-Tesla) to perform magnetic resonance spectroscopy. This technique detects radio frequency electromagnetic signals produced by the atomic nuclei in molecules. This helps scientists to measure what kind of chemicals exist there - and their concentration. This allowed us to detect and measure glutamate and gaba levels separately in different brain regions." Sorry nerd interruption, but this is so cool! "We found an imbalance between glutamate and gaba levels in a group of 31 patients with OCD in the frontal regions of the brain. Specifically, OCD patients had increased levels of glutamate and lower levels of gaba in the anterior cingulate cortex. This means that they had very high levels of neural communication in the area, potentially making it hyperactive." 2020's Investigating the Role of Glutamate in Obsessive-Compulsive Disorder: Current Perspectives concluded "Glutamate appears to play a key role in the development of normal cortico-striato-thalamo-cortical (CSTC) circuits and maintaining a dynamic balance between direct and indirect pathways in health, along with GABA. Variations in genes involved in glutamate signaling and turnover may result in dysfunctional development of CSTC circuits which are thought to underlie the development of OCD. Glutamate has a role to play in immune modulation and is thought to underlie inflammatory processes which result in the development of OCD in some cases. Tight regulation of glutamate also appears to be essential for fear extinction and consolidation of new memories, which are impaired in OCD and result in compulsive behaviors in a bid to reduce fear to get rid of it."