Firas Kareem Al-Kalabi Al-Kalabi (1)
General Background: Type 2 Diabetes Mellitus (T2DM) is a multifactorial metabolic disorder involving genetic and environmental components with chronic low-grade inflammation. Specific Background: Infectious agents such as Toxoplasma gondii and inflammatory cytokine gene variations, including TNF-α -308G/A polymorphism, have been investigated for their association with metabolic disturbances. Knowledge Gap: The combined relationship between T. gondii seropositivity and TNF-α genetic variation in women with T2DM remains insufficiently characterized. Aims: This study aimed to evaluate the association of T. gondii infection and TNF-α -308G/A polymorphism with T2DM in women. Results: In a case-control design involving 480 women, T2DM cases showed higher T. gondii IgG seropositivity (68.3% vs. 45.8%) and elevated IgG titers (47.3 ± 28.6 vs. 32.1 ± 24.8 IU/mL). Additionally, the A allele frequency of TNF-α -308G/A was higher in cases than controls (0.256 vs. 0.208; OR = 1.31, P = 0.047). Novelty: This study integrates parasitic infection status with inflammatory genetic polymorphism in a single analytical framework among women. Implications: Findings suggest that chronic infection and genetic susceptibility are associated with T2DM, supporting further investigation into inflammatory and infectious pathways in metabolic disorders.
Highlights:• Higher IgG seroprevalence observed among diabetic participants• Elevated antibody titers indicate persistent parasitic exposure patterns• Allelic variation linked with increased disease susceptibility
Keywords: Toxoplasma Gondii, Type 2 Diabetes Mellitus, TNF Alpha Polymorphism, Seropositivity, Case Control Study
M. A. B. Khan, M. J. Hashim, J. K. King, R. D. Govender, H. Mustafa, and J. Al Kaabi, “Epidemiology of type 2 diabetes—global burden of disease and forecasted trends,” J. Epidemiol. Glob. Health, vol. 10, no. 1, pp. 107–111, 2020.
G. S. Hotamisligil, “Inflammation, metaflammation and immunometabolic disorders,” Nature, vol. 542, no. 7640, pp. 177–185, 2017.
J. R. Araújo, J. Tomas, C. Brenner, and P. J. Sansonetti, “Impact of high-fat diet on the intestinal microbiota and small intestinal physiology before and after the onset of obesity,” Biochimie, vol. 141, pp. 97–106, 2017.
F. Robert-Gangneux and M. L. Dardé, “Epidemiology of and diagnostic strategies for toxoplasmosis,” Clin. Microbiol. Rev., vol. 25, no. 2, pp. 264–296, 2012.
A. Rostami et al., “Global prevalence of latent toxoplasmosis in pregnant women: A systematic review and meta-analysis,” Clin. Microbiol. Infect., vol. 26, no. 6, pp. 673–683, 2020.
J. Flegr and D. Q. Escudero, “Impaired health status and increased incidence of diseases in Toxoplasma-seropositive subjects—An explorative cross-sectional study,” Parasitology, vol. 143, no. 14, pp. 1974–1989, 2016.
S. Shirbazou, L. Abasian, F. Talebi Meymand, and T. Mazoochi, “Effects of Toxoplasma gondii infection in kidney transplant recipients: A case-control study,” Transpl. Infect. Dis., vol. 19, no. 2, p. e12666, 2017.
H. Majidiani et al., “Is chronic toxoplasmosis a risk factor for diabetes mellitus? A systematic review and meta-analysis of case-control studies,” Braz. J. Infect. Dis., vol. 20, no. 6, pp. 605–609, 2016.
Z. D. Wang et al., “Prevalence and burden of Toxoplasma gondii infection in HIV-infected people: A systematic review and meta-analysis,” Lancet HIV, vol. 4, no. 4, pp. e177–e188, 2017.
C. N. Lumeng and A. R. Saltiel, “Inflammatory links between obesity and metabolic disease,” J. Clin. Invest., vol. 121, no. 6, pp. 2111–2117, 2011.
P. A. Kern, S. Ranganathan, C. Li, L. Wood, and G. Ranganathan, “Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance,” Am. J. Physiol. Endocrinol. Metab., vol. 280, no. 5, pp. E745–E751, 2001.
A. Mahajan et al., “Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps,” Nat. Genet., vol. 50, no. 11, pp. 1505–1513, 2018.
F. Hill-Briggs et al., “Social determinants of health and diabetes: A scientific review,” Diabetes Care, vol. 44, no. 1, pp. 258–279, 2021.
D. Aune et al., “Physical activity and the risk of type 2 diabetes: A systematic review and dose-response meta-analysis,” Eur. J. Epidemiol., vol. 30, no. 7, pp. 529–542, 2015.
A. Wahid et al., “Quantifying the association between physical activity and cardiovascular disease and diabetes: A systematic review and meta-analysis,” J. Am. Heart Assoc., vol. 5, no. 9, p. e002495, 2016.
F. Mauvais-Jarvis, D. J. Clegg, and A. L. Hevener, “The role of estrogens in control of energy balance and glucose homeostasis,” Endocr. Rev., vol. 34, no. 3, pp. 309–338, 2013.
T. Nayeri et al., “The global seroprevalence of anti-Toxoplasma gondii antibodies in women who had spontaneous abortion: A systematic review and meta-analysis,” PLoS Negl. Trop. Dis., vol. 15, no. 4, p. e0009410, 2021.
J. Xiao et al., “Toxoplasma gondii: Biological parameters of the connection to schizophrenia,” Schizophr. Bull., vol. 44, no. 5, pp. 983–992, 2018.
R. N. Feng et al., “BMI is strongly associated with hypertension, and waist circumference is strongly associated with type 2 diabetes and dyslipidemia, in northern Chinese adults,” J. Epidemiol., vol. 26, no. 4, pp. 175–180, 2016.
B. Zhou, J. F. Xiao, L. Tuli, and H. W. Ressom, “LC-MS-based metabolomics,” Mol. BioSyst., vol. 8, no. 2, pp. 470–481, 2012.
L. J. Abraham and J. H. Cho, “Inflammatory bowel disease,” N. Engl. J. Med., vol. 361, no. 21, pp. 2066–2078, 2009.
P. M. Visscher et al., “10 years of GWAS discovery: Biology, function, and translation,” Am. J. Hum. Genet., vol. 101, no. 1, pp. 5–22, 2017.
J. C. Ralston et al., “Fatty acids and NLRP3 inflammasome-mediated inflammation in metabolic tissues,” Annu. Rev. Nutr., vol. 37, pp. 77–102, 2017.
A. Berbudi, N. Rahmadika, A. I. Tjahjadi, and R. Ruslami, “Type 2 diabetes and its impact on the immune system,” Curr. Diabetes Rev., vol. 16, no. 5, pp. 442–449, 2016.
E. K. Shwab et al., “Geographical patterns of Toxoplasma gondii genetic diversity revealed by multilocus PCR-RFLP genotyping,” Parasitology, vol. 141, no. 4, pp. 453–461, 2014.
J. L. Jones and J. P. Dubey, “Foodborne toxoplasmosis,” Clin. Infect. Dis., vol. 55, no. 6, pp. 845–851, 2012.
M. V. Relling and W. E. Evans, “Pharmacogenomics in the clinic,” Nature, vol. 526, no. 7573, pp. 343–350, 2015.