A Systemic Review and Meta-analysis of Human Case -Control Studies Examining the Association between Toxoplasma Gondii and Type 2 Diabetes Mellitus

Aus Molan, Kazunori Nosaka, Michael Hunter and Wei Wanga

Abstract


Type 2 diabetes mellitus (T2DM) continues to be a major challenge for public health authorities worldwide. An emerging field of research is starting to examine the association of infectious and environmental pathogens with diabetes. In particular, the potential of these pathogens to cause low-grade inflammation that may facilitate the risk and development of T2DM. An understudied pathogen of potential interest is the protozoan parasite Toxoplasma gondii (T. gondii). There is some clinical evidence supporting an association between chronic T. gondii infection and the development of T2DM in both animals and humans. The objective of this review is to comprehensively assess the seroprevalence rates of T. gondii in subjects with T2DM in comparison to healthy controls to determine the risk of T2DM due to T. gondii infection. Six electronic databases (Google Scholar, Science Direct, Embase, PubMed, PLOS ONE, and Scopus) were searched using specific Medical Subject Headings terms without language or date restrictions. Fixed and random effects models were used to determine odds ratios with statistical significance being set at 5.0%. Among 1,963 studies, four studies reporting prevalence of T. gondii infection in 1,158 subjects with T2DM and 603 healthy controls met the eligibility criteria. The overall weighted prevalence of T. gondii infection in subjects with T2DM was 55.4% (range: 42.7 - 60.4%) in comparison to 32.1% (range: 21.8 - 50.6%) of healthy controls. Because of significant heterogeneity (Q = 25.529, p <0.001, I2 = 88.25%), the common odds ratio was calculated using a random effects model at 2.34 (95% CI: 1.17 - 4.64, p = 0.016). Regardless of the limited number of studies and a lack of data, T. gondii infection should continue to be regarded as a contributing factor to T2DM disease development. Further high quality studies that include inflammatory biomarker analysis are warranted to determine the specific role of this parasite in the pathogenesis of T2DM.

Keywords


Toxoplasmosis; Toxoplasma gondii; Diabetes Mellitus, Type 2; prevalence; Meta-Analysis.

Full Text:

PDF

References


Shaw J, Tanamas S. Diabetes: the silent pandemic and its impact on Australia Diabetes Australia. 2012. http://healthinfonetecueduau/key–resources/bibliography/?lid=22970. Accessed 2 May 2017.

American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2008;31:S55–60.

Diabetes Australia. Diabetes in Australia. 2015. http://diabetesaustraliacomau/diabetes–in–australia. Accessed 13 April 2017.

Donath MY, Ehses JA, Maedler K, Schumann DM, Ellingsgaard H, Eppler R, Reinecke M. Mechanisms of β–Cell Death in Type 2 Diabetes. Diabetes. 2005;54:S108.

Prandota J. T gondii Infection Acquired during Pregnancy and/or after Birth may be Responsible for Development of both Type 1 and 2 Diabetes Mellitus. Journal of Diabetes and Metabolism. 2013;4:1000241.

Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27:1047–1053.

Lipscombe LL, Hux JE. Trends in diabetes prevalence incidence and mortality in Ontario Canada 1995–2005: a population–based study. Lancet. 2007;369:750–756.

International Diabetes Federation (IDF). Diabetes Atlas (sixth edition). 2013. http://idforg/sites/default/files/EN_6E_Atlas_Full_0pdf. Accessed 24 April 2017.

World Health Organization. Global Health Estimates: Deaths by Cause Age Sex and Country 2000–2012. WHO, Geneva. 2014a. http://whoint/healthinfo/global_burden_disease/en/. Accessed 14 April 2017.

World Health Organization Global status report on noncommunicable diseases. WHO, Geneva. 2014b. http://whoint/nmh/publications/ncd–status–report–2014/en/. Accessed 14 April 2017.

International Diabetes Federation (IDF). Diabetes Atlas (seventh edition). 2015. http://diabetesatlasorg/. Accessed 24 April 2017.

World Health Organization. Diabetes program. WHO, Geneva. 2015. http://whoint/diabetes/en/. Accessed 14 April 2017.

Pradhan A. Obesity metabolic syndrome and type 2 diabetes: inflammatory basis of glucose metabolic disorders. Nutrition Reviews. 2007;65:S152–6.

Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. Journal of Clinical Investigations. 2006;116:179–1801.

Nicolle C, Manceaux L. Sur une infection a` corps de Leishman (ou organismes voisins) du gondi. Comptes Rendus de l'Académie des Sciences. 1908;147:763–766. (In French)

Pappas G, Roussos N, Falagas ME. Toxoplasmosis snapshots: global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis. International Journal of Parasitology. 2009;39:1385–1394.

Peng HJ, Chen XC, Lindsay DS. A review: competence compromise and concomitance–reaction of the host cell to Toxoplasma gondii infection and development. Journal of Parasitology. 2011;94:620–628.

Halonen SK, Weiss LM. Toxoplasmosis. In: Garcia HH, Tanowitz HB, Del Brutto OH, editors. Handbook of Clinical Neurology, Neuroparasitology and Tropical Neurology, Vol 114 (3rd series). Amsterdam: Elsevier BV, Amsterdam; 2013. P. 125–145.

Centers for Disease Control and Prevention. Parasites - Toxoplasmosis (Toxoplasma infection). 2015. http://cdcgov/parasites/toxoplasmosis/epihtml.Accessed 22 April 2017.

Tenter A, Heckeroth A, Weiss M. Toxoplasma gondii: from animals to humans. International Journal of Parasitology. 2000;30:1217–1258.

Parlog A, Schluter D, Dunay IR. Toxoplasma gondii–induced neuronal alterations. Parasite Immunology. 2015;37:159–170.

Cong W, Liu GH, Meng QF, Dong W, Qin SY, Zhang FK, Zhang XY, Wang XY, Qian AD, Zhu XQ. Toxoplasma gondii infection in cancer patients: Prevalence risk factors genotypes and association with clinical diagnosis. Cancer Letters. 2015;259:307–313.

Robert–Gangneux F, Dardé ML. Epidemiology of and diagnostic strategies for toxoplasmosis. Clinical Microbiology Reviews. 2012;25:264–96.

Dandona P, Aljada A, Bandyopadhyay A. Inflammation: the link between insulin resistance obesity and diabetes. Trends in Immunology. 2004;25:4–7.

Kankova S, Flegr J, Calda P. An elevated blood glucose level and increased incidence of gestational diabetes mellitus in pregnant woman with latent toxoplasmosis. Folia Parasitlogica. 2015;62:056.

Dupey JP. The History of Toxoplasma gondii– The First 100 Years. Journal of Eukaryotic Microbiology. 2008;55:467–475.

Albuquerque MC, Aleixo AL, Benchimol EI, Leandro AC, das Neves LB, Vicente RT, Bonecini-Almeida Mda G, Amendoeira MR. The IFN–gamma +874T/A gene polymorphism is associated with retinochoroiditis toxoplasmosis susceptibility. Memórias do Instituto Oswaldo Cruz. 2009;104:451–455.

Hunter CA. Sibley LD Modulation of innate immunity by Toxoplasma gondii virulence effectors. Nature Reviews. 2012;10:766–788.

Montoyoa JG. Laboratory Diagnosis of Toxoplasma gondii Infection and Toxoplasmosis. Journal of Infectious Diseases. 2002;85:S73–82.

Henriques SA, Brett R, Alexander J, Pratt J, Roberts CW. Neuropsychiatric Disease and Toxoplasma gondii infection. Neuroimmunomodulation. 2009;16:122–133

Molan A, Nosaka K, Hunter M, Wang W. The role of Toxoplasma gondii as a possible inflammatory agent in the pathogenesis of Type 2 Diabetes Mellitus in humans. Family Medicine and Community Health. 2016;4:44–62.

Moher D, Liberati A, Tetzlaff J, Altman DG. The PRISMA Group Preferred Reporting Items for Systematic Reviews and Meta–Analyses: The PRISMA Statement. PLOS Medicine. 2009. doi:101371/journalpmed1000097.

Modrek MJ, Saravani R, Mousavi M, Khorashad AS, Piri M. Investigation of IgG and IgM Antibodies Against Toxoplasma gondii Among Diabetic Patients. International Journal of Infection. 2015. doi: 1017795/iji27595.

Gocke C, Yazar S, Bayram F, Gundogan K, Yaman O, Sahin I. Anti–Toxoplasma gondii antibodies in type 2 diabetes. National Medical Journal of India. 2008;21:51.

Siyadatpanah A, Tabatabaie F, Oormazdi H, Meamar AH, Razmjou E, Hadighi R, Akhlaghi L. Comparison of anti–toxoplasma IgG and IgM antibodies determined by ELISA method in diabetic and non–diabetic individuals in west Mazandaran province Iran 2011–2012. Annals of Biological Research. 2013;4:281–285.

Shirbazou S, Delpisheh A, Mokhetari R, Tavakoli G. Serologic Detection of Anti Toxoplasma gondii Infection in Diabetic Patients. Iranian Red Crescent Medical Journal. 2013;15:701–703.

Saki J, Shafieenia S, Foroutan-Rad M. Seroprevalence of toxoplasmosis in diabetic pregnant women in southwestern of Iran. Journal of Parasitic Diseases. 2016;40:1586–1589.

Majidiani H, Dalvand S, Daryani A, Galvan–Ramirezd MDL, Foroutan–Rad M. Is chronic toxoplasmosis a risk factor for diabetes mellitus? A systematic review and meta–analysis of case–control studies. Brazilian Journal of Infectious Diseases. 2016;20:605–609.

Spranger J, Kroke A, Mo¨hlig M, Hoffmann K, Bergmann MM, Ristow M, Boeing H, Pfeiffer A F. Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population–based European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam Study. Diabetes. 2003;52:812–817.

Chagas CEA, Borges MC, Martini LA, Rogero MM. Focus on Vitamin D inflammation and Type 2 Diabetes. Nutrients. 2012;4:52–67.

Pickup JC, Crook MA. Is type II diabetes mellitus a disease of the innate immune system? Diabetologia. 1998;41:1241–1248.

Grimble RF. Inflammatory status and insulin resistance. Current Opinion in Clinical Nutrition and Metabolic Care. 2002;5:551–559.

Pickup JC. Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care. 2004;27:813–823.

Tilg H, Moschen AR. Inflammatory mechanisms in the regulation of insulin resistance. Molecular Medicine. 2008;14:222–231.

Herder C, Zierer A, Koenig W, Roden M, Meisinger C, Thorand B. Transforming growth factor–beta1 and incident type 2 diabetes: results from the MONICA/KORA case–cohort study 1984–2002. Diabetes Care. 2009;32:1921–1923.

Jagannathan M, McDonnell M, Liang Y, Hasturk H, Hetzel J, Rubin D, Kantarci A, Van Dyke TE, Ganley-Leal LM, Nikolajczyk BS. Toll–like receptors regulate B cell cytokine production in patients with diabetes. Diabetologia. 2012;53:1461–1471.

Jagannathan M, McDonnell ME, Shin H, Rehman Q, Hasturk H, Apovian CM, Nikolajczyk BS. Elevated Proinflammatory Cytokine Production by a Skewed T Cell Compartment Requires Monocytes and Promotes Inflammation in Type 2 Diabetes. Journal of Immunology. 2011;186:1162–1172.

Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nature Reviews Immunology. 2011;11:98–107.

Ramadan JW, Steiner SR, O'Neill CM, Nunemaker CS. The central role of calcium in the effects of cytokines on beta–cell function: implications for type 1 and type 2 diabetes. Cell Calcium. 2011;50:481–90.

Oz HS, Tobin T. Atovaquone ameliorate gastrointestinal toxoplasmosis complications in a pregnancy model. Medical Science Monitor. 2012;18:BR337–345.

Coppari R, Bjørbæk C. The Potential of Leptin for Treating Diabetes and Its Mechanism of Action. Nature Reviews Drug Discovery. 2012;11:692–70.

Baltaci AK, Mogulkoc R. Plasma leptin levels in rats with induced Toxoplasma gondii infection. Bratislava Medical Journal. 2012;113:67–69.

Flegr J. Influence of latent Toxoplasma infection on human personality physiology and morphology: pros and cons of the Toxoplasma–human model in studying the manipulation hypothesis. Journal of Experimental Biology. 2013;216:127–133.

Sakuraba H, Mizukami H, Yagihashi N, Wada R, Hanyu C, Yagihashi S. Reduced beta–cell mass and expression of oxidative stress–related DNA damage in the islet of Japanese type II diabetic patients. Diabetologia. 2002;45:85–96.

Yoon KH, Ko SH, Cho JH, Lee JM, Ahn YB, Song KH, Yoo SJ, Kang MI, Cha BY, Lee KW, Son HY, Kang SK, Kim HS, Lee IK, Bonner-Weir S. Selective beta–cell loss and alpha–cell expansion in patients with type 2 diabetes mellitus in Korea. The Journal of Clinical Endocrinology and Metabolism. 2003;88:2300–2308.

Butler AE, Janson J Bonner–Weir S, Ritzel R, Rizza RA, Butle PC. Beta–cell deficit and increased beta–cell apoptosis in humans with type 2 diabetes. Diabetes. 2013;52:102–110.

Gonzalez–Perez A, Schlienger RG, Rodríguez LA. Acute Pancreatitis in Association with Type 2 Diabetes and Antidiabetic Drugs A population–based cohort study. Diabetes Care. 2010;33:2580–2585.

Waree P. Toxoplasmosis: Pathogenesis and immune response. Thammasat Medical Journal. 2008;8:487–496.

Dupont CD, Christian DA, Hunter CA. Immune response and immunopathology during toxoplasmosis. Seminars in Immunopathology. 2012;34:793–813.

Oz HS. Toxoplasmosis Pancreatitis Obiesty and Drug Discovery. Pancreatic Disorders and Therapy. 2014;4:138.

Hassanain MA, El–Fadaly HA, Hassanain NA. Toxoplasma gondii parasite load elevation in diabetic rats as latent opportunistic character. Annals of Tropical Medicine and Public Health. 2014;7:110–115.

Daryani A, Sarvi S, Aarabi M, Mizani A, Ahmadpour E, Shokri A, Rahimi MT, Sharif M. Seroprevalence of Toxoplasma gondii in the Iranian general population: a systematic review and meta–analysis. Acta Tropica. 2014;37:185–94.

Carter CJ. Toxoplasmosis and Polygenic Disease Susceptibility Genes: Extensive Toxoplasma gondii Host/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders. Journal of Pathology. 2013;965046.

Reeves GM, Mazaheri S, Snitker S, Langenberg P, Giegling I, Hartmann A, Konte B, Friedl M, Okusaga O, Groer MW, Mangge H, Weghuber D, Allison DB, Rujescu D, Postolache1 TT. A positive association between T gondii seropositivity and obesity. Frontiers in Public Health. 2013. doi:103389/fpubh201300073.

Bessman AN, Sapico FL. Infections in the diabetic patient: the role of immune dysfunction and pathogen virulence factors. Journal of Diabetes Complications. 1992;6:258–262.

Nazligulm Y, Sabuncu T, Ozbilge H. Is There a Predisposition to Intestinal Parasitosis in Diabetic Patients? Diabetes Care. 2001;24:1503–1504.

Zhu S, Lai D, Li S, Lun Z. Simulative effects of insulin on Toxoplasma gondii replication in 3T3–L1 cells. Cell Biology International. 2006;30:149–153.

Akinbo FO, Olujobi SO, Omoregie R, Egbe E. Intestinal parasitic infections among diabetes mellitus patients Biomark. Genomic Medicine. 2013;5:44–47.

Mohtashamipour M, Hoseini SG, Pestehchian N, Yousefi H, Fallah E, Hazratatian T. Intestinal parasitic infections in patients with Diabetes Mellitus: A case–control study. Journal of Analytical Research in Clinical Medicine. 2015;3:157–63.


Refbacks

  • There are currently no refbacks.


Copyright (c) 2018 American Journal of Life Science Researches

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

  

© DIILI PUBLICATION