Abstract
Type 2 diabetes mellitus (T2DM) is a major global health problem. The rate of infection with Toxoplasma gondii (T. gondii) is more than one-third of the total world population. The effects of T. gondii infection on the risk of diabetic complications and comorbidities are unclear. This study aims to determine the relationship between T. gondii infection and complications of T2DM in the Han Chinese population. We collected 1580 blood samples from T2DM patients and measured the levels of specific IgG antibodies against T. gondii in the sera of these patients using an ELISA assay. A logistic regression analysis was performed to estimate the effect of T. gondii infection on the complications of T2DM, while adjusting for age, gender, and triglyceride level (TG). We applied the multifactor dimensionality reduction (MDR) method to detect the interactions between T. gondii infections, demographic indexes and biochemical indicators among the different complications. Gender (the odds ratio (OR) = 0.63, 95%CI =0.45–0.89, P = 0.008) and TG level (OR = 0.64, 95%CI =0.45–0.89, P = 0.009) were influencing factors in T. gondii infections. T2DM patients who were infected with T. gondii had a 2.34 times risk of developing hypertension than those patients without T. gondii infection (OR = 2.34, 95%CI = 1.12–4.88, P = 0.024). The multiplicative interaction analysis and the additive interaction analysis did not reveal any evidence of interactive effects on diabetic complications and comorbidities. T. gondii might be a factor associated with hypertension in T2DM patients.
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Alvarado-Esquivel C, Vazquez-Alaniz F, Sandoval-Carrillo AA, Salas-Pacheco JM, Hernandez-Tinoco J, Sanchez-Anguiano LF, Liesenfeld O (2014) Lack of association between Toxoplasma gondii infection and hypertensive disorders in pregnancy: a case-control study in a Northern Mexican population. Parasit Vectors 7(1):167. https://doi.org/10.1186/1756-3305-7-167
American Diabetes Association (ADA) (2016) Diabetes guidelines summary recommendations from National Diabetes Education Initiative [NDEI]. Retrieved from http://www.ndei.org/ADA-diabetes-management-guidelines-diagnosis-A1C-testing.aspx
Basavaraju A (2016) Toxoplasmosis in HIV infection: an overview. Trop Parasitol 6(2):129–135. https://doi.org/10.4103/2229-5070.190817
Boia MN, Carvalho-Costa FA, Sodre FC, Pinto GM, Amendoeira MR (2008) Seroprevalence of Toxoplasma gondii infection among indian people living in Iauarete, Sao Gabriel da Cachoeira, Amazonas, Brazil. Rev Inst Med Trop Sao Paulo 50(1):17–20. https://doi.org/10.1590/S0036-46652008000100004
Boothroyd JC, Grigg ME (2002) Population biology of Toxoplasma gondii and its relevance to human infection: do different strains cause different disease? Curr Opin Microbiol 5(4):438–442. https://doi.org/10.1016/S1369-5274(02)00349-1
Chalmers J (1999) The 1999 WHO-ISH Guidelines for the Management of Hypertension. Med J Aust 171(9):458–459
Darde ML (2004) Genetic analysis of the diversity in Toxoplasma gondii. Ann Ist Super Sanita 40(1):57–63
Dyck PJ, Litchy WJ, Lehman KA, Hokanson JL, Low PA, O'Brien PC (1995) Variables influencing neuropathic endpoints: the Rochester diabetic neuropathy study of healthy subjects. Neurology 45(6):1115–1121. https://doi.org/10.1212/WNL.45.6.1115
Ferrannini E, Cushman WC (2012) Diabetes and hypertension: the bad companions. Lancet 380(9841):601–610. https://doi.org/10.1016/s0140-6736(12)60987-8
Ferreira MS, Borges AS (2002) Some aspects of protozoan infections in immunocompromised patients- a review. Mem Inst Oswaldo Cruz 97(4):443–457. https://doi.org/10.1590/S0074-02762002000400001
Flegr J, Prandota J, Sovickova M, Israili ZH (2014) Toxoplasmosis—a global threat. Correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries. PLoS One 9(3):e90203. https://doi.org/10.1371/journal.pone.0090203
Gao XJ et al (2012) Toxoplasma gondii infection in pregnant women in China. Parasitology 139(02):139–147. https://doi.org/10.1017/s0031182011001880
Gokce C, Yazar S, Bayram F, Gundogan K, Yaman O, Sahin I (2008) Anti-Toxoplasma gondii antibodies in type 2 diabetes. Natl Med J India 21:51
Guo C, Zhang L, Nie L, Zhang N, Xiao D, Ye X, Ou M, Liu Y, Zhang B, Wang M, Lin H, Yang G, Jing C (2016) Association of polymorphisms in the MyD88, IRAK4 and TRAF6 genes and susceptibility to type 2 diabetes mellitus and diabetic nephropathy in a southern Han Chinese population. Mol Cell Endocrinol 429:114–119. https://doi.org/10.1016/j.mce.2016.04.003
Huang WH, Nie LH, Zhang LJ, Jing LP, Dong F, Wang M, Zhang N, Liu Y, Zhang BH, Chen C, Lin HS, Wei XC, Yang G, Jing CX (2015) Association of TLR2 and TLR4 non-missense single nucleotide polymorphisms with type 2 diabetes risk in a southern Chinese population: a case-control study. Genet Mol Res 14(3):8694–8705. https://doi.org/10.4238/2015.July.31.18
Jones JL, Muccioli C, Belfort R Jr, Holland GN, Roberts JM, Silveira C (2006) Recently acquired Toxoplasma gondii infection, Brazil. Emerg Infect Dis 12(4):582–587. https://doi.org/10.3201/eid1204.051081
Jones JL, Kruszon-Moran D, Sanders-Lewis K, Wilson M (2007) Toxoplasma gondii infection in the United States, 1999 2004, decline from the prior decade. Am J Trop Med Hyg 77(3):405–410
Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN (2009) Hyperglycemic crises in adult patients with diabetes. Diabetes Care 32(7):1335–1343. https://doi.org/10.2337/dc09-9032
Lampe MA, Burlingame AL, Whitney J, Williams ML, Brown BE, Roitman E, Elias PM (1983) Human stratum corneum lipids: characterization and regional variations. J Lipid Res 24(2):120–130
Lee J (1981) Covariance adjustment of rates based on the multiple logistic regression model. J Chronic Dis 34(8):415–426. https://doi.org/10.1016/0021-9681(81)90040-0
Mendez-Samperio P, de-la-Rosa-Arana JL (2015) Prevention of type 1 diabetes through parasite infection. Immunotherapy 7(6):595–598. https://doi.org/10.2217/imt.15.34
Montoya JG, Liesenfeld O (2004) Toxoplasmosis. Lancet 363(9425):1965–1976. https://doi.org/10.1016/s0140-6736(04)16412-x
Muller LM, Gorter KJ, Hak E, Goudzwaard WL, Schellevis FG, Hoepelman AI, Rutten GE (2005) Increased risk of common infections in patients with type 1 and type 2 diabetes mellitus. Clin Infect Dis 41(3):281–288. https://doi.org/10.1086/431587
Munoz M, Liesenfeld O, Heimesaat MM (2011) Immunology of toxoplasma gondii. Immunol Rev 240(1):269–285. https://doi.org/10.1111/j.1600-065X.2010.00992.x
Patel RS, Asselbergs FW, Quyyumi AA, Palmer TM, Finan CI, Tragante V, Deanfield J, Hemingway H, Hingorani AD, Holmes MV (2014) Genetic variants at chromosome 9p21 and risk of first versus subsequent coronary heart disease events: a systematic review and meta-analysis. J Am Coll Cardiol 63(21):2234–2245. https://doi.org/10.1016/j.jacc.2014.01.065
Ritchie MD, Hahn LW, Roodi N, Bailey LR, Dupont WD, Parl FF, Moore JH (2001) Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet 69(1):138–147. https://doi.org/10.1086/321276
Saki J, Khademvatan S, Soltani S, Shahbazian H (2013) Detection of toxoplasmosis in patients with end-stage renal disease by enzyme-linked immunosorbent assay and polymerase chain reaction methods. Parasitol Res 112(1):163–168. https://doi.org/10.1007/s00436-012-3120-6
Saki J, Shafieenia S, Foroutan-Rad M (2016) Seroprevalence of toxoplasmosis in diabetic pregnant women in southwestern of Iran. J Parasit Dis 40(4):1586–1589. https://doi.org/10.1007/s12639-015-0735-4
Shin JJ, Lee EK, Park TJ, Kim W (2015) Damage-associated molecular patterns and their pathological relevance in diabetes mellitus. Ageing Res Rev 24(Pt A):66–76. https://doi.org/10.1016/j.arr.2015.06.004
Shirbazou S, Delpisheh A, Mokhetari R, Tavakoli G (2013) Serologic detection of anti Toxoplasma gondii infection in diabetic patients. Iran Red Crescent Med J 15(8):701–703. https://doi.org/10.5812/ircmj.5303
Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR (2000) Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321(7258):405–412. https://doi.org/10.1136/bmj.321.7258.405
Sun LL, Zhang SJ, Chen MJ, Elena K, Qiao H (2017) Relationship between modulator recognition factor 2/AT-rich interaction domain 5B gene variations and type 2 diabetes mellitus or lipid metabolism in a northern Chinese population. Chin Med J 130(9):1055–1061. https://doi.org/10.4103/0366-6999.204926
Tang Q, Sun Z, Zhang N, Xu G, Song P, Xu L, Tang W (2016) Cost-effectiveness of bariatric surgery for type 2 diabetes mellitus: a randomized controlled trial in China. Medicine (Baltimore) 95(20):e3522. https://doi.org/10.1097/md.0000000000003522
Wang L, Chen H, Liu D, Huo X, Gao J, Song X, Xu X, Huang K, Liu W, Wang Y, Lu F, Lun ZR, Luo Q, Wang X, Shen J (2013) Genotypes and mouse virulence of toxoplasma gondii isolates from animals and humans in China. PLoS One 8(1):e53483. https://doi.org/10.1371/journal.pone.0053483
Wellen KE, Hotamisligil GS (2005) Inflammation, stress, and diabetes. J Clin Invest 115(5):1111–1119. https://doi.org/10.1172/jci25102
Xiao Y, Yin J, Jiang N, Xiang M, Hao L, Lu H, Sang H, Liu X, Xu H, Ankarklev J, Lindh J, Chen Q (2010) Seroepidemiology of human Toxoplasma gondii infection in China. BMC Infect Dis 10(1):4. https://doi.org/10.1186/1471-2334-10-4
Yang W, Weng J (2014) Early therapy for type 2 diabetes in China. Lancet Diabetes Endocrinol 2(12):992–1002. https://doi.org/10.1016/s2213-8587(14)70136-6
Yang W, Lu J, Weng J, Jia W, Ji L, Xiao J, Shan Z, Liu J, Tian H, Ji Q, Zhu D, Ge J, Lin L, Chen L, Guo X, Zhao Z, Li Q, Zhou Z, Shan G, He J, China National Diabetes and Metabolic Disorders Study Group (2010) Prevalence of diabetes among men and women in China. N Engl J Med 362(12):1090–1101. https://doi.org/10.1056/NEJMoa0908292
Young MJ, Boulton AJ, MacLeod AF, Williams DR, Sonksen PH (1993) A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia 36(2):150–154. https://doi.org/10.1007/BF00400697
Zhou P, Chen Z, Li HL, Zheng H, He S, Lin RQ, Zhu XQ (2011) Toxoplasma gondii infection in humans in China. Parasit Vectors 4(1):165. https://doi.org/10.1186/1756-3305-4-165
Zhu S, Lai DH, Li SQ, Lun ZR (2006) Stimulative effects of insulin on Toxoplasma gondii replication in 3T3-L1 cells. Cell Biol Int 30(2):149–153. https://doi.org/10.1016/j.cellbi.2005.09.004
Funding
This work was supported in part by the Major Research Plan of the National Natural Science Foundation of China (91543132), National Natural Science Foundation of China (grant nos: 81541070, 30901249, and 81101267), the Guangdong Natural Science Foundation (grant nos: 10151063201000036, S2011010002526, and 2016A030313089), Guangdong Province Medical Research Foundation (grant nos: A2014374, A2015310), and Project from Jinan university (grant nos: 21612426, 21615426, JNUPHPM2016001, and JNUPHPM2016002).
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Han, Y., Nie, L., Ye, X. et al. The association between Toxoplasma gondii infection and hypertensive disorders in T2DM patients: a case-control study in the Han Chinese population. Parasitol Res 117, 689–695 (2018). https://doi.org/10.1007/s00436-017-5737-y
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DOI: https://doi.org/10.1007/s00436-017-5737-y