Academic Journal
Multi-metal co-exposure and type 2 diabetes: integrating biomonitoring evidence, inflammatory mechanisms, and a framework for future risk stratification.
| Τίτλος: | Multi-metal co-exposure and type 2 diabetes: integrating biomonitoring evidence, inflammatory mechanisms, and a framework for future risk stratification. |
|---|---|
| Συγγραφείς: | Mishra RK; Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, Vaishali, Bihar, 844102, India., Roy S; Biological Engineering, Lousiana State University, Baton Rouge, LA, USA., Mishra A; Department of Biomedical Science, Dr. B.R. Ambedkar Centre for Biomedical Research (ACBR), Delhi, India., Prakash V; Department of Endocrinology, Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, Bihar, India., Shekhar R; Department of Biochemistry, Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, Bihar, India., Kumar N; Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, Bihar, India., Murti K; Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, Vaishali, Bihar, 844102, India. krishnamurti@niperhajipur.ac.in. |
| Πηγή: | Environmental geochemistry and health [Environ Geochem Health] 2026 Oct 04; Vol. 48 (15). Date of Electronic Publication: 2026 Oct 04. |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Kluwer Academic Publishers Country of Publication: Netherlands NLM ID: 8903118 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-2983 (Electronic) Linking ISSN: 02694042 NLM ISO Abbreviation: Environ Geochem Health Subsets: MEDLINE |
| Imprint Name(s): | Publication: 1999- : Dordrecht : Kluwer Academic Publishers Original Publication: Kew, Surrey : Science and Technology Letters, 1985- |
| Ιατρικοί όροι (MeSH): | Diabetes Mellitus, Type 2*/chemically induced , Diabetes Mellitus, Type 2*/epidemiology , Diabetes Mellitus, Type 2*/metabolism , Metals, Heavy*/toxicity , Metals, Heavy*/analysis , Biological Monitoring*/methods , Environmental Exposure*/adverse effects , Environmental Pollutants*/toxicity , Environmental Pollutants*/analysis, Inflammation/chemically induced ; Humans ; Risk Assessment ; Oxidative Stress |
| Περίληψη: | Diabetes Mellitus Type 2 prevalence is still increasing around the world, and there is growing evidence of the role of environmental co-exposures to heavy metals-cadmium, lead, arsenic, mercury, and chromium-in glycaemia impairment. Contrarily to studies on single metal toxicology, real-life situations consist in exposure to mixtures of heavy metals through environmental, occupational and dietary pathways, especially in places like the Indo-Gangetic plain of India, characterized by the presence of geological arsenic pollution in association with metals exposure. This paper provides a narrative review on the current state of art in the domain of three key issues connected to risk stratification in Type 2 Diabetes Mellitus: methods for biomonitoring metals, inflammatory and molecular pathways involved in diabetes onset and progression related to metal exposures and statistical approaches for modeling joint effects of mixtures. Firstly, discuss on the biomonitoring methods, with particular emphasis to blood, urine and hair and nail as classical matrices and new emerging matrices (saliva, buccal cells). The analytical technique (AAS vs ICP-MS) is considered as well. It will focus on the heterogeneity between different methodologies, including matrix-specific exposure window and inter-laboratory variability. Regarding mechanistic aspects, there is an agreement in scientific literature on several molecular pathways involved in glycaemia alterations, including oxidative stress, NF-κB inflammation pathway, mitochondria dysfunction, epigenetics alteration and insulin signaling impairment, with possible synergistic rather than additive action of heavy metals in the impairment of beta-cell function and insulin resistance. Finally, it discusses some recent advances in quantifying joint metal effects on diabetes through specific statistics as WQS regression and Bayesian Kernel Machine regression (BKMR) and quantile g-computation. Even though important methodological advances have been made, a translational gap remains: no validated procedure currently exists that integrates exposure metrics, inflammatory biomarkers and clinical variables for individual risk stratification. We therefore outline a research-stage framework that could guide future development of such tools. (© 2026. The Author(s), under exclusive licence to Springer Nature B.V.) |
| Competing Interests: | Declarations. Conflict of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Use of Artificial Intelligence: The authors declare that no generative artificial intelligence (AI) tools were used to generate or write the scientific content of this manuscript. All scientific interpretation, literature synthesis, and manuscript preparation were performed by the authors. Schematic figures were created using BioRender and subsequently edited and finalized by the authors. |
| References: | Alves, A., Kucharska, A., Erratico, C., Xu, F., Hond, E., Koppen, G., et al. (2014). Human biomonitoring of emerging pollutants through non-invasive matrices: State of the art and future potential. Analytical & Bioanalytical Chemistry, 406(17), 4063. (PMID: 10.1007/s00216-014-7748-1) Basil, B., & Okoro, P. N. (2026). Metabolic-associated steatotic liver disease in children and adolescents: A scoping review and narrative synthesis of epidemiology, risk factors, and screening approaches with emerging implications for sub-Saharan Africa. Frontiers in Endocrinology, 17, 1784970. (PMID: 10.3389/fendo.2026.1784970) Batra, J., Thakur, A., Meena, S. K., Singh, L., Kumar, J., & Juyal, D. (2020). Blood lead levels among the occupationally exposed workers and its effect on calcium and vitamin D metabolism: A case-control study. Journal of Family Medicine and Primary Care, 9(5), 2388. (PMID: 10.4103/jfmpc.jfmpc_271_20) Bellanti, F., Coda, A. R. D., Trecca, M. I., Lo Buglio, A., Serviddio, G., & Vendemiale, G. (2025). Redox imbalance in inflammation: The interplay of oxidative and reductive stress. Antioxidants, 14(6), 656. (PMID: 10.3390/antiox14060656) Briffa, J. (2020). Heavy metals in Maltese agricultural soil (Master’s Thesis). University of Malta. Retrieved from https://www.um.edu.mt/library/oar/handle/123456789/73391. Butler, O. T., Cairns, W. R., Cook, J. M., & Davidson, C. M. (2017). Atomic spectrometry update–a review of advances in environmental analysis. Journal of Analytical Atomic Spectrometry, 32(1), 11–57. (PMID: 10.1039/C6JA90058E) Cai, J., Li, Y., Liu, S., Liu, Q., Zhang, J., Wei, Y., et al. (2022). Associations between multiple heavy metals exposure and glycated hemoglobin in a Chinese population. Chemosphere, 287, 132159. (PMID: 10.1016/j.chemosphere.2021.132159) Carli, M. (2023). Model-based Imputation of below detection limit missing data and group selection in Bayesian group index regression. https://scholarscompass.vcu.edu/etd/7439/ . Accessed 4 July 2026. Chen, Y. W., Yang, C. Y., Huang, C. F., Hung, D. Z., Leung, Y. M., & Liu, S. H. (2009). Heavy metals, islet function and diabetes development. Islets, 1(3), 169–176. https://doi.org/10.4161/isl.1.3.9262. (PMID: 10.4161/isl.1.3.9262) Chojnacka, K., & Mikulewicz, M. (2018). Biomarkers of trace element status. In K. Chojnacka & A. Saeid (Eds.), Recent advances in trace elements (1st ed., pp. 457–467). Wiley. https://doi.org/10.1002/9781119133780.ch22. (PMID: 10.1002/9781119133780.ch22) Christman, J. W., Blackwell, T. S., & Juurlink, B. H. J. (2000). Redox regulation of nuclear factor kappa B: Therapeutic potential for attenuating inflammatory responses. Brain Pathology, 10(1), 153–162. https://doi.org/10.1111/j.1750-3639.2000.tb00252.x. (PMID: 10.1111/j.1750-3639.2000.tb00252.x) Clases, D., & de Vega, R. G. (2022). Facets of ICP-MS and their potential in the medical sciences—Part 1: Fundamentals, stand-alone and hyphenated techniques. Analytical and Bioanalytical Chemistry, 414(25), 7337. (PMID: 10.1007/s00216-022-04259-1) Cortés, S., Zúñiga-Venegas, L., Pancetti, F., Covarrubias, A., Ramírez-Santana, M., Adaros, H., & Muñoz, L. (2021). A positive relationship between exposure to heavy metals and development of chronic diseases: A case study from Chile. International Journal of Environmental Research and Public Health, 18(4), 1419. (PMID: 10.3390/ijerph18041419) De Paula Nunes, E., Abou Dehn Pestana, B., & Pereira, B. B. (2026). Human biomonitoring and environmental health: A critical review of global exposure patterns, methodological challenges and research gaps. Journal of Toxicology and Environmental Health, Part B, Critical Reviews, 29(2), 109–127. https://doi.org/10.1080/10937404.2025.2529845. (PMID: 10.1080/10937404.2025.2529845) Deng, P., Li, X., Petriello, M. C., Wang, C., Morris, A. J., & Hennig, B. (2019). Application of metabolomics to characterize environmental pollutant toxicity and disease risks. Reviews on Environmental Health, 34(3), 251–259. https://doi.org/10.1515/reveh-2019-0030. (PMID: 10.1515/reveh-2019-0030) Duncan, B. B., Magliano, D. J., & Boyko, E. J. (2026). IDF diabetes atlas 11th edition 2025: Global prevalence and projections for 2050. Nephrology Dialysis Transplantation. Oxford University Press. https://academic.oup.com/ndt/advance-article-pdf/doi/ https://doi.org/10.1093/ndt/gfaf177/64148213/gfaf177.pdf . Accessed 1 July 2026. El Balkhi, S., & Machon, C. (2022). Toxicology of heavy metals in biological matrices: A paradigm shift from single-analyte measurement to comprehensive screening. Therapeutic Drug Monitoring. https://doi.org/10.1097/ftd.0000000000001416. (PMID: 10.1097/ftd.0000000000001416) European Food Safety Authority (EFSA), Bastaki M, Eskes C, Halldorsson T, Muñoz Guajardo IP, Vejdovszky K, Viviani B, Steinkellner H (2026) Statement on the findings presented in the Toxicological Profile for Mercury issued by the US ATSDR. EFSA Journal, 24(6), e10156. Feigin, V. L., Roth, G. A., Naghavi, M., Parmar, P., Krishnamurthi, R., Chugh, S., et al. (2016). Global burden of stroke and risk factors in 188 countries, during 1990–2013: A systematic analysis for the Global Burden of Disease Study 2013. The Lancet Neurology, 15(9), 913–924. (PMID: 10.1016/S1474-4422(16)30073-4) Filippini, T., Wise, L. A., Vinceti, M. (2022) Cadmium exposure and risk of diabetes and prediabetes: A systematic review and dose-response meta-analysis. Environment International, 158, 106920. Flora, S. J. S., Mittal, M., & Mehta, A. (2008). Heavy metal induced oxidative stress & its possible reversal by chelation therapy. Indian Journal of Medical Research, 128(4), 501–523. Fu, J., Woods, C. G., Yehuda-Shnaidman, E., Zhang, Q., Wong, V., Collins, S., et al. (2010). Low-level arsenic impairs glucose-stimulated insulin secretion in pancreatic beta cells: Involvement of cellular adaptive response to oxidative stress. Environmental Health Perspectives, 118(6), 864. (PMID: 10.1289/ehp.0901608) Gadelmawla, A. F., Alsubaiei, A. A., AlSejari, N. Y., Alkuwaiti, M. A., Mahafdah, B., Abdul-Hafez, H. A., et al. (2026). Interpretable machine learning in heavy metal-associated cardiovascular and metabolic disease: A review of current methodologies, toxicological insights, and clinical implications. Cardiovascular Toxicology, 26(6), 64. https://doi.org/10.1007/s12012-026-10142-7. (PMID: 10.1007/s12012-026-10142-7) Gao, T., Lv, J., Lu, L., Guo, L., Tang, W., Shao, F., et al. (2024). Role of urinary trace elements in diabetic kidney disease: A cross-sectional analysis. BMJ Open Diabetes Research & Care. https://doi.org/10.1136/bmjdrc-2024-004454. (PMID: 10.1136/bmjdrc-2024-004454) Gilles, L., Govarts, E., Rodriguez Martin, L., Andersson, A.-M., Appenzeller, B. M., Barbone, F., et al. (2022). Harmonization of human biomonitoring studies in Europe: Characteristics of the HBM4EU-aligned studies participants. International Journal of Environmental Research and Public Health, 19(11), 6787. (PMID: 10.3390/ijerph19116787) Gong, B., Qiu, H., Romero-Freire, A., Van Gestel, C. A. M., & He, E. (2022). Incorporation of chemical and toxicological availability into metal mixture toxicity modeling: State of the art and future perspectives. Critical Reviews in Environmental Science and Technology, 52(10), 1730–1772. https://doi.org/10.1080/10643389.2020.1862560. (PMID: 10.1080/10643389.2020.1862560) Goyal, T., Mitra, P., Singh, P., Sharma, S., & Sharma, P. (2021). Assessement of blood lead and cadmium levels in occupationally exposed workers of Jodhpur, Rajasthan. Indian Journal of Clinical Biochemistry, 36(1), 100–107. (PMID: 10.1007/s12291-020-00878-6) Hamilton, E. M., Young, S. D., Bailey, E. H., & Watts, M. J. (2018). Chromium speciation in foodstuffs: A review. Food Chemistry, 250, 105–112. (PMID: 10.1016/j.foodchem.2018.01.016) Hassan, N. E., Nakhaee, S., Manoochehri, Z., Bousaeedi, A., Mansouri, B., & Rezaei, A. (2025). Serum levels of trace elements in diabetic pregnant women and their relationship with growth indicators in newborns. Scientific Reports, 15(1), 18382. (PMID: 10.1038/s41598-025-03239-6) He, L., He, T., Farrar, S., Ji, L., Liu, T., & Ma, X. (2017). Antioxidants maintain cellular redox homeostasis by elimination of reactive oxygen species. Cellular Physiology and Biochemistry, 44(2), 532–553. https://doi.org/10.1159/000485089. (PMID: 10.1159/000485089) Hernández, A. F., Gil, F., & Lacasaña, M. (2017). Toxicological interactions of pesticide mixtures: An update. Archives of Toxicology, 91(10), 3211–3223. https://doi.org/10.1007/s00204-017-2043-5. (PMID: 10.1007/s00204-017-2043-5) Himani, K. R., Ansari, J. A., Mahdi, A. A., Sharma, D., Karunanand, B., & Datta, S. K. (2020). Blood lead levels in occupationally exposed workers involved in battery factories of Delhi-NCR region: Effect on vitamin D and calcium metabolism. Indian Journal of Clinical Biochemistry, 35(1), 80–87. (PMID: 10.1007/s12291-018-0797-z) Hong, F., Jin, T., & Zhang, A. (2004). Risk assessment on renal dysfunction caused by co-exposure to arsenic and cadmium using benchmark dose calculation in a Chinese population. BioMetals, 17(5), 573–580. https://doi.org/10.1023/B:BIOM.0000045741.22924.d8. (PMID: 10.1023/B:BIOM.0000045741.22924.d8) Hoskovec, L., Benka-Coker, W., Severson, R., Magzamen, S., & Wilson, A. (2021). Model choice for estimating the association between exposure to chemical mixtures and health outcomes: A simulation study. PLoS ONE, 16(3), e0249236. (PMID: 10.1371/journal.pone.0249236) Javaid, A., Akbar, I., Javed, H., Khan, U., Iftikhar, H., Zahra, D., et al. (2021). Role of heavy metals in diabetes: Mechanisms and treatment strategies. Critical Reviews in Eukaryotic Gene Expression. https://doi.org/10.1615/critreveukaryotgeneexpr.2021037971. (PMID: 10.1615/critreveukaryotgeneexpr.2021037971) Junaid, M., Hashmi, M. Z., Malik, R. N., & Pei, D.-S. (2016). Toxicity and oxidative stress induced by chromium in workers exposed from different occupational settings around the globe: A review. Environmental Science and Pollution Research, 23(20), 20151–20167. https://doi.org/10.1007/s11356-016-7463-x. (PMID: 10.1007/s11356-016-7463-x) Karri, V., Kumar, V., Ramos, D., Oliveira, E., & Schuhmacher, M. (2018). Comparative in vitro toxicity evaluation of heavy metals (lead, cadmium, arsenic, and methylmercury) on HT-22 hippocampal cell line. Biological Trace Element Research, 184(1), 226. (PMID: 10.1007/s12011-017-1177-x) Kavitha, S. A., Zainab, S., Muthyalaiah, Y. S., John, C. M., & Arockiasamy, S. (2025). Mechanism and implications of advanced glycation end products (AGE) and its receptor RAGE axis as crucial mediators linking inflammation and obesity. Molecular Biology Reports, 52(1), 556. (PMID: 10.1007/s11033-025-10632-x) Keane, K. N., Cruzat, V. F., Carlessi, R., De Bittencourt, P. I. H., & Newsholme, P. (2015). Molecular events linking oxidative stress and inflammation to insulin resistance and β-cell dysfunction. Oxidative Medicine and Cellular Longevity. https://doi.org/10.1155/2015/181643. (PMID: 10.1155/2015/181643) Kruger, P. C., Bloom, M. S., Arnason, J. G., Palmer, C. D., Fujimoto, V. Y., & Parsons, P. J. (2012). Trace elements in human follicular fluid: Development of a sensitive multielement ICP-MS method for use in biomonitoring studies. Journal of Analytical Atomic Spectrometry, 27(8), 1245–1253. (PMID: 10.1039/C2JA30053B) Kumar, A., Rahman, M. S., Ali, M., Salaun, P., Gourain, A., Kumar, S., et al. (2022). Assessment of disease burden in the arsenic exposed population of Chapar village of Samastipur district, Bihar, India, and related mitigation initiative. Environmental Science and Pollution Research, 29(18), 27443–27459. (PMID: 10.1007/s11356-021-18207-6) Kumar, P., Khan, P. K., & Kumar, A. (2025). Health risk assessment upon exposure to groundwater arsenic among individuals of different sex and age groups of Vaishali district, Bihar (India). Toxicology Reports, 14, 102024. (PMID: 10.1016/j.toxrep.2025.102024) Laoye, B., Olagbemide, P., Ogunnusi, T., & Akpor, O. (2025). Heavy metal contamination: Sources, health impacts, and sustainable mitigation strategies with insights from Nigerian case studies. F1000Research, 14, 134. (PMID: 10.12688/f1000research.160148.3) Ley, S. H., Hamdy, O., Mohan, V., & Hu, F. B. (2014). Prevention and management of type 2 diabetes: Dietary components and nutritional strategies. Lancet, 383(9933), 1999–2007. (PMID: 10.1016/S0140-6736(14)60613-9) Li, L., & Yang, X. (2018). The essential element manganese, oxidative stress, and metabolic diseases: Links and interactions. Oxidative Medicine and Cellular Longevity, 2018(1), 7580707. https://doi.org/10.1155/2018/7580707. (PMID: 10.1155/2018/7580707) Li, Y., Chai, J., Chen, J., Du, J., Mu, J., & Zhang, L. (2025). The AST/ALT ratio as a mediator of heavy metal exposure and diabetic kidney disease (DKD) risk: A NHANES study. Scientific Reports, 15(1), 40137. (PMID: 10.1038/s41598-025-23843-w) Liu, B., Li, K., & Pang, T. (2025). Bayesian smoothed quantile regression. arXiv preprint arXiv:2508.01738 . https://arxiv.org/abs/2508.01738 . Accessed 4 July 2026. Liu, J., & Wu, L. (2025). Heavy metal pollution and ischemic stroke: Multimechanistic pathogenesis and countermeasures. Frontiers in Public Health, 13, 1650999. (PMID: 10.3389/fpubh.2025.1650999) Liu, S., Chen, X., Qi, X., Bai, J., Tong, B., Zhang, D., et al. (2025b). The role of metal ion metabolism in the pathogenesis of diabetes and associated complications. Frontiers in Endocrinology, 16, Article 1541809. (PMID: 10.3389/fendo.2025.1541809) Lobinski, R., Moulin, C., & Ortega, R. (2006). Imaging and speciation of trace elements in biological environment. Biochimie, 88(11), 1591–1604. (PMID: 10.1016/j.biochi.2006.10.003) Malerba, M., Purghè, B., Ragnoli, B., Manfredi, M., & Baldanzi, G. (2025). Molecular profiling of exhaled breath condensate in respiratory diseases. Annals of Medicine, 57(1), 2537910. https://doi.org/10.1080/07853890.2025.2537910. (PMID: 10.1080/07853890.2025.2537910) Mandal, B. K., Suzuki, K. T., & Anzai, K. (2007). Impact of arsenic in foodstuffs on the people living in the arsenic-affected areas of West Bengal, India. Journal of Environmental Science and Health, Part a, Toxic/hazardous Substances & Environmental Engineering, 42(12), 1741–1752. https://doi.org/10.1080/10934520701564244. (PMID: 10.1080/10934520701564244) Manoochehri, Z., Nakhaee, S., Azadi, N. A., Davarinezhad, O., Ariyaee, M., & Mansouri, B. (2025). Association between trace elements and sleep duration in patients with type 2 diabetes mellitus: Evidence from a Kurdish population in Western Iran. Biological Trace Element Research, 204(5), 3245–3252. https://doi.org/10.1007/s12011-025-04889-3. (PMID: 10.1007/s12011-025-04889-3) Mansouri, B., Rezaei, A., Sharafi, K., Azadi, N., Pirsaheb, M., Rezaei, M., & Nakhaee, S. (2024). Mixture effects of trace element levels on cardiovascular diseases and type 2 diabetes risk in adults using G-computation analysis. Scientific Reports, 14(1), 5743. (PMID: 10.1038/s41598-024-56468-6) Mattei, J., Malik, V., Wedick, N. M., Hu, F. B., Spiegelman, D., et al. (2015). Global Nutrition Epidemiologic Transition Initiative Reducing the global burden of type 2 diabetes by improving the quality of staple foods: The Global Nutrition and Epidemiologic Transition Initiative. Globalization and Health, 11(1), 23. https://doi.org/10.1186/s12992-015-0109-9. (PMID: 10.1186/s12992-015-0109-9) Maull, E. A., Ahsan, H., Edwards, J., Longnecker, M. P., Navas-Acien, A., Pi, J., et al. (2012). Evaluation of the association between arsenic and diabetes: A National Toxicology Program workshop review. Environmental Health Perspectives, 120(12), 1658. (PMID: 10.1289/ehp.1104579) Mazumder, D. N. G., Deb, D., Biswas, A., Saha, C., Nandy, A., Ganguly, B., et al. (2013). Evaluation of dietary arsenic exposure and its biomarkers: A case study of West Bengal, India. Journal of Environmental Science and Health, Part a, Toxic/hazardous Substances & Environmental Engineering, 48(8), 896–904. https://doi.org/10.1080/10934529.2013.761495. (PMID: 10.1080/10934529.2013.761495) Medunić, G., Fiket, Ž, & Ivanić, M. (2020). Arsenic contamination status in Europe, Australia, and other parts of the world. In S. Srivastava (Ed.), Arsenic in drinking water and food (pp. 183–233). Springer Singapore. https://doi.org/10.1007/978-981-13-8587-2_6. (PMID: 10.1007/978-981-13-8587-2_6) Michalke, B. (2022). Review about powerful combinations of advanced and hyphenated sample introduction techniques with inductively coupled plasma-mass spectrometry (ICP-MS) for elucidating trace element species in pathologic conditions on a molecular level. International Journal of Molecular Sciences, 23(11), 6109. (PMID: 10.3390/ijms23116109) Munir, N., Jahangeer, M., Bouyahya, A., El Omari, N., Ghchime, R., Balahbib, A., et al. (2021). Heavy metal contamination of natural foods is a serious health issue: A review. Sustainability, 14(1), 161. (PMID: 10.3390/su14010161) Narayanan, M. (2026). Heavy metal exposure among industrial workers mechanisms of toxicity biomonitoring strategies and public health risk assessment. Discover Public Health, 23(1), 146. https://doi.org/10.1186/s12982-026-01431-1. (PMID: 10.1186/s12982-026-01431-1) Neale, R. E., Barnes, P. W., Robson, T. M., Neale, P. J., Williamson, C. E., Zepp, R. G., Wilson, S. R., Madronich, S, Andrady, A. L., Heikkilä, A. M., Bernhard, G. H. (2021) Environmental effects of stratospheric ozone depletion, UV radiation, and interactions with climate change: UNEP Environmental Effects Assessment Panel, Update 2020. Photochemical & Photobiological Sciences, 20(1), 1–67. Newtonraj, A., & Kannan, K. S. (2024). Time series forecasting and projection of diabetes prevalence in India from 2023 to 2035: A cross-sectional study. Journal of Clinical & Diagnostic Research, 18(10). https://search.ebscohost.com/login.aspx?direct=true&profile=ehost&scope=site&authtype=crawler&jrnl=0973709X&AN=180690118&h=%2BrVFoq7ImmN%2BW83T9YCCD%2B4EwAUye4ZDuGu2FqJG8xREBEDSUUUytvdPNpAaEgyQt3XX8hZ1VC0GFchkMX53lg%3D%3D&crl=c . Accessed 1 July 2026. Nguyen, H. D. (2023). An evaluation of the effects of mixed heavy metals on prediabetes and type 2 diabetes: Epidemiological and toxicogenomic analysis. Environmental Science and Pollution Research, 30(34), 82437–82457. https://doi.org/10.1007/s11356-023-28037-3. (PMID: 10.1007/s11356-023-28037-3) Norwood, W. P., Borgmann, U., Dixon, D. G., & Wallace, A. (2003). Effects of metal mixtures on aquatic biota: A review of observations and methods. Human and Ecological Risk Assessment: An International Journal, 9(4), 795–811. https://doi.org/10.1080/713610010. (PMID: 10.1080/713610010) Pannucci, E., Spagnuolo, L., De Gara, L., Santi, L., & Dugo, L. (2023). Phenolic compounds as preventive and therapeutic agents in diabetes-related oxidative stress, inflammation, advanced glycation end-products production and insulin sensitivity. Discovery medicine, 35(178). https://www.iris.unicampus.it/handle/20.500.12610/83723 . Accessed 1 July 2026. Papp, J. R. (2024). CDC laboratory recommendations for syphilis testing, United States, 2024. MMWR. Recommendations and Reports, 73. Parsons, P. J., & Barbosa, F., Jr. (2007). Atomic spectrometry and trends in clinical laboratory medicine. Spectrochimica Acta Part B: Atomic Spectroscopy, 62(9), 992–1003. (PMID: 10.1016/j.sab.2007.03.007) Paustenbach, D., Finley, B., Mowat, F., & Kerger, B. (2003). Human health risk and exposure assessment of chromium (VI) in tap water. Journal of Toxicology and Environmental Health, Part A, 66(14), 1295–1339. https://doi.org/10.1080/15287390306388. (PMID: 10.1080/15287390306388) Podgorski, J., & Berg, M. (2022). Global analysis and prediction of fluoride in groundwater. Nature Communications, 13(1), 4232. (PMID: 10.1038/s41467-022-31940-x) Praamsma, M. L., Arnason, J. G., & Parsons, P. J. (2011). Monitoring Mn in whole blood and urine: A comparison between electrothermal atomic absorption and inorganic mass spectrometry. Journal of Analytical Atomic Spectrometry, 26(6), 1224–1232. (PMID: 10.1039/c1ja10039d) Price, N. F. (2025). Environmental Metal Mixtures, Body Composition, and Insulin Resistance in African Caribbean Adults: Findings from the Tobago Health Study (PhD Thesis). University of Pittsburgh. Retrieved from https://search.proquest.com/openview/a077bf321e8a114fb8d862e8ede1fa13/1?pq-origsite=gscholar&cbl=18750&diss=y. Qureshi, K., & Abrams, G. A. (2007). Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease. World Journal of Gastroenterology: WJG, 13(26), 3540. (PMID: 10.3748/wjg.v13.i26.3540) Rahman, A., & Guillemin, G. J. (2021). Lead and excitotoxicity. In R. M. Kostrzewa (Ed.), Handbook of neurotoxicity (pp. 1–39). Springer International Publishing. https://doi.org/10.1007/978-3-030-71519-9_142-1. (PMID: 10.1007/978-3-030-71519-9_142-1) Ramakrishnan, B., Megharaj, M., Venkateswarlu, K., Sethunathan, N., & Naidu, R. (2011). Mixtures of environmental pollutants: Effects on microorganisms and their activities in soils. In D. M. Whitacre (Ed.), Reviews of environmental contamination and toxicology (Vol. Vol. 211, pp. 63–120). Springer New York. https://doi.org/10.1007/978-1-4419-8011-3_3. (PMID: 10.1007/978-1-4419-8011-3_3) Rasool, A., Pertile, E., Brožová, K., Halfar, J., Čabanová, K., Malíková, P., et al. (2026). Mechanistic insights and environmental ramifications of Cr(III) oxidation to Cr(VI) in soil and groundwater systems: Bridging geochemical mechanisms and emerging remediation strategies. Environmental Geochemistry and Health, 48(1), Article 12. https://doi.org/10.1007/s10653-025-02901-2. (PMID: 10.1007/s10653-025-02901-2) Rice, K. M., Walker, E. M., Jr., Wu, M., Gillette, C., & Blough, E. R. (2014). Environmental mercury and its toxic effects. Journal of Preventive Medicine & Public Health, 47(2), 74. (PMID: 10.3961/jpmph.2014.47.2.74) Rius-Pérez, S., Pérez, S., Martí-Andrés, P., Monsalve, M., & Sastre, J. (2020). Nuclear factor kappa B signaling complexes in acute inflammation. Antioxidants & Redox Signaling, 33(3), 145–165. https://doi.org/10.1089/ars.2019.7975. (PMID: 10.1089/ars.2019.7975) Rob, A., Hoque, A., Asaduzzaman, M. M., Khatoon, M. A. A., Khalil, R., Thomas, D., et al. (2025). The global challenges of type 2 diabetes. Bangladesh Journal of Medicine, 36(2), 92–98. (PMID: 10.3329/bjm.v36i2.78406) Saha, R., Nandi, R., & Saha, B. (2011). Sources and toxicity of hexavalent chromium. Journal of Coordination Chemistry, 64(10), 1782–1806. https://doi.org/10.1080/00958972.2011.583646. (PMID: 10.1080/00958972.2011.583646) Samples, S. S. G. (2026). Agency for toxic substances and disease registry (ATSDR) newsletter for health assessors, including APPLETREE partners. https://www.atsdr.cdc.gov/pha-guidance/resources/ATSDR-Newsletter-for-Healh-Assessors-May-2022-508.pdf . Accessed 4 July 2026. Santonen, T., Schoeters, G., & Nordberg, M. (2022). Biological monitoring of metals and biomarkers. In Handbook on the Toxicology of Metals (pp. 217–235). Elsevier. https://www.sciencedirect.com/science/article/pii/B9780128232927000073 . Accessed 25 September 2026. Sarigiannis, D., Karakitsios, S., Anesti, O., Stem, A., Valvi, D., Sumner, S. C. J., et al. (2025). Advancing translational exposomics: Bridging genome, exposome and personalized medicine. Human Genomics, 19(1), 48. https://doi.org/10.1186/s40246-025-00761-6. (PMID: 10.1186/s40246-025-00761-6) Sauliutė, G., & Svecevičius, G. (2015). Heavy metal interactions during accumulation via direct route in fish: A review. Zoology and Ecology, 25(1), 77–86. Schiavo, B., Meza-Figueroa, D., Vizuete-Jaramillo, E., Robles-Morua, A., Angulo-Molina, A., Reyes-Castro, P. A., et al. (2023). Oxidative potential of metal-polluted urban dust as a potential environmental stressor for chronic diseases. Environmental Geochemistry and Health, 45(6), 3229–3250. (PMID: 10.1007/s10653-022-01403-9) Sies, H., Berndt, C., & Jones, D. P. (2017). Oxidative stress. Annual Review of Biochemistry, 86(1), 715–748. https://doi.org/10.1146/annurev-biochem-061516-045037. (PMID: 10.1146/annurev-biochem-061516-045037) Sikdar, S., & Kundu, M. (2018). A review on detection and abatement of heavy metals. ChemBioEng Reviews, 5(1), 18–29. https://doi.org/10.1002/cben.201700005. (PMID: 10.1002/cben.201700005) Taylor, A., Barlow, N., Day, M. P., Hill, S., Martin, N., & Patriarca, M. (2019). Atomic spectrometry update: Review of advances in the analysis of clinical and biological materials, foods and beverages. Journal of Analytical Atomic Spectrometry, 34(3), 426–459. (PMID: 10.1039/C9JA90004G) Theodorsson, E., Magnusson, B., & Leito, I. (2014). Bias in Clinical Chemistry. Bioanalysis, 6(21), 2855–2875. https://doi.org/10.4155/bio.14.249. (PMID: 10.4155/bio.14.249) Tinajero, M. G., & Malik, V. S. (2021). An update on the epidemiology of type 2 diabetes: A global perspective. Endocrinology and Metabolism Clinics, 50(3), 337–355. (PMID: 10.1016/j.ecl.2021.05.013) Truong, N. N., Tesfamariam, K., Visintin, L., Goessens, T., De Saeger, S., Lachat, C., & De Boevre, M. (2022). Associating multiple mycotoxin exposure and health outcomes: Current statistical approaches and challenges. World Mycotoxin Journal, 16(1), 25–32. (PMID: 10.3920/WMJ2022.2784) Uddin, S., Afroz, H., Hossain, M., Briffa, J., Blundell, R., & Islam, M. R. (2023). Heavy metals/metalloids in food crops and their implications for human health. In M. A. Hossain, A. Z. Hossain, S. Bourgerie, M. Fujita, O. P. Dhankher, & P. Haris (Eds.), Heavy metal toxicity and tolerance in plants (1st ed., pp. 59–86). Wiley. https://doi.org/10.1002/9781119906506.ch3. (PMID: 10.1002/9781119906506.ch3) Urbanowicz, T., & Filipiak, K. J. (2026). From exposure to outcome: Air pollution-induced oxidative stress as a determinant of early and late outcomes after coronary artery bypass grafting. Antioxidants, 15(8), 930. (PMID: 10.3390/antiox15080930) Vasudevan, S. A., Seenivasan, S. N., Raghupathy, A. K., Vasudevan, D., Ayothi, P., Nayak, T., et al. (2026). Association of urine heavy metals with prevalence of type 1 diabetes and poor glycaemic control. Biological Trace Element Research, 204(5), 3426–3436. (PMID: 10.1007/s12011-025-04903-8) Venugopal, V., Richa, R., Singh, D., Gautam, A., & Jahnavi, G. (2023). National programme for prevention and control of cancer, diabetes, cardiovascular diseases, and stroke: A scoping review in the context of hypertension prevention and control in India. Indian Journal of Public Health, 67(Suppl 1), S50–S57. (PMID: 10.4103/ijph.ijph_681_23) Waalkes, M. P., Coogan, T. P., & Barter, R. A. (1992). Toxicological principles of metal carcinogenesis with special emphasis on cadmium. Critical Reviews in Toxicology, 22(3–4), 175–201. https://doi.org/10.3109/10408449209145323. (PMID: 10.3109/10408449209145323) Wang, M., Wang, X., Li, X., Dong, Y., Yu, J., Li, P., et al. (2025). Chenopodium album L herb attenuates inflammation by modulating multiple signaling pathways in zebrafish: Network pharmacology analysis, transcriptomics analysis and experimental verification. Journal of Functional Foods, 127, 106719. (PMID: 10.1016/j.jff.2025.106719) Wang, X., Liu, L., Xie, K., Feng, X., Gao, L., Sun, M., et al. (2026). Cross-regional assessment of heavy metal contamination and Cd exceedance risk in specialty vegetable-producing soils across China. Environmental Research. https://doi.org/10.1016/j.envres.2026.124540. (PMID: 10.1016/j.envres.2026.124540) Wang, Y., Xu, A., Ye, J., Kraegen, E. W., Tse, C. A., & Cooper, G. J. (2001). Alteration in phosphorylation of P20 is associated with insulin resistance. Diabetes, 50(8), 1821–1827. (PMID: 10.2337/diabetes.50.8.1821) Warkentin, M. T., Al-Sawaihey, H., Lam, S., Liu, G., Diergaarde, B., Yuan, J.-M., et al. (2024). Radiomics analysis to predict pulmonary nodule malignancy using machine learning approaches. Thorax, 79(4), 307–315. (PMID: 10.1136/thorax-2023-220226) Welsh, N. (2017). Department of medical cell biology: Annual report 2016. Uppsala University. https://www.diva-portal.org/smash/get/diva2:1119869/FULLTEXT01.pdf . Accessed 4 July 2026. Wu, K., Chen, Y., & Huang, W. (2025). Combined molecular toxicity mechanism of heavy metals mixtures. In D. Pei & Y. Liu (Eds.), Toxicological assessment of combined chemicals in the environment (1st ed., pp. 125–172). Wiley. https://doi.org/10.1002/9781394158355.ch09. (PMID: 10.1002/9781394158355.ch09) Wu, X., Cobbina, S. J., Mao, G., Xu, H., Zhang, Z., & Yang, L. (2016). A review of toxicity and mechanisms of individual and mixtures of heavy metals in the environment. Environmental Science and Pollution Research, 23(9), 8244–8259. https://doi.org/10.1007/s11356-016-6333-x. (PMID: 10.1007/s11356-016-6333-x) Wu, X., Zhou, Y., Nie, Y., Xu, H., Liu, H., Cheng, M., et al. (2026). Organophosphate flame retardants and incident type 2 diabetes: Integrating population evidence, mechanistic insights, and effect modification by healthy lifestyle. Journal of Hazardous Materials, 516, 143347. (PMID: 10.1016/j.jhazmat.2026.143347) Wu, Xiaofei, Sun, Y., Zhou, W., Liu, Q., Xie, L., Zhang, M., et al. (n.d.). Effect and Regulatory Mechanism of Serum Metal Mixtures on Childhood Blood Pressure: from a Cohort and Multi-omics Analyses. Available at SSRN 6724475. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=6724475 . Accessed 4 July 2026. Yang, Y., Li, C., Zhang, D., Sheng, Y., Jiang, Q., Luo, X., et al. (2025). Association between mixed urinary metal exposure and metabolic syndrome in the population of Guangxi, China: Mechanistic insights from a case-control study. Ecotoxicology and Environmental Safety, 307, 119435. (PMID: 10.1016/j.ecoenv.2025.119435) Zainith, S. (2024). Sources and pathways of heavy metals and their persistence in ecosystems. Heavy metal contamination in the environment (pp. 19–33). CRC Press. Zhang, J., Yin, H., Zhu, X., Xiang, R., Miao, Y., Zhang, Y., et al. (2022). Effects of multi‐metal exposure on the risk of diabetes mellitus among people aged 40–75 years in rural areas in southwest China. Journal of Diabetes Investigation, 13(8), 1412–1425. https://doi.org/10.1111/jdi.13797. (PMID: 10.1111/jdi.13797) Zhang, S., Tang, H., Pan, L., & Zhou, M. (2025). Association of metal and metalloid exposure with cardiovascular-kidney-metabolic syndrome: Mediation by inflammation, oxidative stress, and aging. BMC Public Health, 26(1), 222. https://doi.org/10.1186/s12889-025-25894-0. (PMID: 10.1186/s12889-025-25894-0) Zheng, Y., Lin, P.-I.D., Williams, P. L., Weisskopf, M. G., Cardenas, A., Rifas-Shiman, S. L., et al. (2021). Early pregnancy essential and non-essential metal mixtures and gestational glucose concentrations in the 2nd trimester: Results from project viva. Environment International, 155, 106690. (PMID: 10.1016/j.envint.2021.106690) Zia, B., AlKaabi, J., Agha, A., Sharma, C., & Ali, B. R. (2026). The diabetes exposome: interplay of environmental and genetic determinants in diabetes. Human Genomics. https://link.springer.com/content/pdf/10.1186/s40246-026-00987-y_reference.pdf. Accessed 4 July 2026. |
| Contributed Indexing: | Keywords: Biomonitoring; Heavy metal mixtures; Inflammation; Mixture modelling; Oxidative stress; Risk stratification; Type 2 diabetes mellitus |
| Substance Nomenclature: | 0 (Metals, Heavy) 0 (Environmental Pollutants) |
| Entry Date(s): | Date Created: 20261004 Date Completed: 20261004 Latest Revision: 20261004 |
| Update Code: | 20261005 |
| DOI: | 10.1007/s10653-026-03518-9 |
| PMID: | 42829886 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1573-2983 |
|---|---|
| DOI: | 10.1007/s10653-026-03518-9 |