{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:13:17Z","timestamp":1789996397687,"version":"4.0.1"},"reference-count":37,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U22A20360"],"award-info":[{"award-number":["U22A20360"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["U22A20360"],"award-info":[{"award-number":["U22A20360"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Scientific Research Project of Ningxia Medical University","award":["XT2023012"],"award-info":[{"award-number":["XT2023012"]}],"id":[{"id":"https:\/\/ror.org\/02h8a1848","id-type":"ROR","asserted-by":"crossref"}]},{"award":["XT2023012"],"award-info":[{"award-number":["XT2023012"]}],"id":[{"id":"https:\/\/ror.org\/02h8a1848","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Objective: Current evidence on the association between multiple trace elements and type 2 diabetes mellitus (T2DM) remains limited, particularly regarding combined effects, nonlinear dose\u2013response patterns, and elemental interactions. This study aimed to evaluate the associations between multiple serum trace elements and T2DM using a sequential analytical strategy. Methods: A 1:1 propensity score\u2013matched case\u2013control study based on sex, age, and residence was conducted (637 controls, 637 T2DM cases). Serum concentrations of 18 trace elements were measured using inductively coupled plasma mass spectrometry (ICP-MS). A sequential analytical strategy was applied: LASSO regression for variable selection; logistic regression with single-element (Model 1) and multi-element (Models 2 and 3) approaches for association assessment; weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) for mixture effects; and restricted cubic spline (RCS) for dose\u2013response patterns. Results: Lithium (Li) and tellurium (Te) showed positive associations with T2DM across multiple analytical methods, whereas boron (B), lead (Pb), and vanadium (V) showed inverse associations. WQS identified V and B as the main contributing elements. BKMR did not identify a statistically significant overall association between the mixture and T2DM. Although bivariate interaction plots suggested possible effect modification between V and Al, B, Li, Pb, and Te, formal interaction tests did not reach statistical significance. RCS showed that serum B was significantly associated with T2DM overall and exhibited a significant non-linear dose\u2013response relationship (P-nonlinear = 0.0028). Serum V showed a linear inverse association with T2DM, and serum Li showed a linear positive association. Conclusions: Our findings suggest that Li, Te, B, and V are associated with T2DM, with the most robust evidence for Li, while the evidence for Te was less consistent. In addition, we observed a trend toward a joint association of the trace element mixture, potential effect modification at the point-estimate level between V and Al, B, Li, Pb, and Te, and distinct dose\u2013response patterns for B, Li, and V. These findings highlight the need for further investigation of trace elements in relation to T2DM, with consideration of both individual and combined associations; future validation of these exploratory findings in larger prospective studies and independent populations is warranted.<\/jats:p>","DOI":"10.3390\/nu18183068","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:50:03Z","timestamp":1789995003000},"page":"3068","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum Levels of 18 Trace Elements and Type 2 Diabetes Mellitus: A Propensity Score-Matched Case\u2013Control Study in Northwest Chinese Adults"],"prefix":"10.3390","volume":"18","author":[{"given":"Lu","family":"Ma","sequence":"first","affiliation":[{"name":"School of Public Health, Ningxia Medical University, No. 1160 Shengli Street, Xingqing District, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianglong","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Public Health, Ningxia Medical University, No. 1160 Shengli Street, Xingqing District, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boqian","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Public Health, Ningxia Medical University, No. 1160 Shengli Street, Xingqing District, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Public Health, Ningxia Medical University, No. 1160 Shengli Street, Xingqing District, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxing","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Ningxia Medical University, No. 1160 Shengli Street, Xingqing District, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0958-0350","authenticated-orcid":false,"given":"Yi","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Public Health, Ningxia Medical University, No. 1160 Shengli Street, Xingqing District, Yinchuan 750004, China"},{"name":"Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Public Health, Ningxia Medical University, No. 1160 Shengli Street, Xingqing District, Yinchuan 750004, China"},{"name":"Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Professional Practice Committee (2025). 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2025. Diabetes Care, 48, S27\u2013S49.","DOI":"10.2337\/dc25-S002"},{"key":"ref_2","unstructured":"Magliano, D.J., and Boyko, E.J. (2021). IDF Diabetes Atlas 10th edition scientific committee. IDF DIABETES ATLAS, International Diabetes Federation."},{"key":"ref_3","first-page":"159","article-title":"Epidemiology of diabetes mellitus: Prevalence, incidence, pathogenesis, and prognosis","volume":"96","author":"Janka","year":"2002","journal-title":"Z. Arztl. Fortbild. Qualitatssich."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1210\/endrev\/bnad030","article-title":"Protective Factors and the Pathogenesis of Complications in Diabetes","volume":"45","author":"Yu","year":"2024","journal-title":"Endocr. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"117941","DOI":"10.1016\/j.ecoenv.2025.117941","article-title":"Associations of multiple plasma metals with the risk of type 2 diabetes in Chinese adults: A cross-sectional study","volume":"292","author":"Yang","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"113325","DOI":"10.1016\/j.envpol.2019.113325","article-title":"Association between exposure to arsenic, nickel, cadmium, selenium, and zinc and fasting blood glucose levels","volume":"255","author":"Li","year":"2019","journal-title":"Environ. Pollut."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12937-016-0169-6","article-title":"Association between serum selenium level and type 2 diabetes mellitus: A non-linear dose-response meta-analysis of observational studies","volume":"15","author":"Wang","year":"2016","journal-title":"Nutr. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"111210","DOI":"10.1016\/j.envres.2021.111210","article-title":"A systematic review and dose-response meta-analysis of exposure to environmental selenium and the risk of type 2 diabetes in nonexperimental studies","volume":"197","author":"Vinceti","year":"2021","journal-title":"Environ. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.envpol.2018.01.046","article-title":"Associations of multiple plasma metals with incident type 2 diabetes in Chinese adults: The Dongfeng-Tongji Cohort","volume":"237","author":"Yuan","year":"2018","journal-title":"Environ. Pollut."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1038\/s41598-025-31637-3","article-title":"Associations of metal mixtures with insulin resistance and glucose homeostasis in U.S. adults from the NHANES 2011\u20132018","volume":"16","author":"Wu","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1002\/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S","article-title":"Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation","volume":"15","author":"Alberti","year":"1998","journal-title":"Diabet. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1289\/ehp.7199","article-title":"Epidemiologic evaluation of measurement data in the presence of detection limits","volume":"112","author":"Lubin","year":"2004","journal-title":"Environ. Health Perspect."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1007\/s10534-022-00419-z","article-title":"Associations between whole blood trace elements concentrations and HbA1c levels in patients with type 2 diabetes","volume":"35","author":"Luan","year":"2022","journal-title":"Biometals"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"118802","DOI":"10.1016\/j.foodres.2026.118802","article-title":"Dietary zinc antagonism of selenium toxicity in a natural seleniferous region: Insights from bioaccessibility, risk assessment, and biomarker verification","volume":"231","author":"Zhou","year":"2026","journal-title":"Food Res. Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.clnu.2007.10.003","article-title":"Acute inflammatory response does not affect erythrocyte concentrations of copper, zinc and selenium","volume":"27","author":"Oakes","year":"2008","journal-title":"Clin. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.taap.2009.04.020","article-title":"Current status of cadmium as an environmental health problem","volume":"238","author":"Akesson","year":"2009","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"327","DOI":"10.5271\/sjweh.2404","article-title":"Biological half-time of cadmium in the blood of workers after cessation of exposure","volume":"9","author":"Rogenfelt","year":"1983","journal-title":"Scand. J. Work Environ. Health"},{"key":"ref_18","first-page":"699","article-title":"Cadmium and lead in blood in relation to low bone mineral density and tubular proteinuria","volume":"110","author":"Elinder","year":"2002","journal-title":"Environ. Health Perspect."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/bdi.13308","article-title":"Pharmacological treatment of bipolar disorder and risk of diabetes mellitus: A nationwide study of 30,451 patients","volume":"25","author":"Rohde","year":"2023","journal-title":"Bipolar Disord."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0304-4165(00)00068-4","article-title":"Effects of lithium and insulin on glycogen synthesis in L6 myocytes: Additive effects on inactivation of glycogen synthase kinase-3","volume":"1475","author":"Choi","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0006-291X(70)90760-6","article-title":"Inhibition of thyrotropin-stimulated adenyl cyclase activity of beef thyroid membranes by low concentration of lithium ion","volume":"39","author":"Wolff","year":"1970","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"436","DOI":"10.18632\/aging.100468","article-title":"The Tellurium compound, AS101, increases SIRT1 level and activity and prevents type 2 diabetes","volume":"4","author":"Gertler","year":"2012","journal-title":"Aging"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S1357-2725(98)00113-7","article-title":"Binding of tellurium to hepatocellular selenoproteins during incubation with inorganic tellurite: Consequences for the activity of selenium-dependent glutathione peroxidase","volume":"31","author":"Garberg","year":"1999","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jtemb.2017.03.001","article-title":"Trace element status in patients with type 2 diabetes in Norway: The HUNT3 Survey","volume":"41","author":"Hansen","year":"2017","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jtemb.2016.12.008","article-title":"Trace elements in early phase type 2 diabetes mellitus-A population-based study. The HUNT study in Norway","volume":"40","author":"Hansen","year":"2017","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1007\/s00394-021-02730-w","article-title":"Plasma boron concentrations in the general population: A cross-sectional analysis of cardio-metabolic and dietary correlates","volume":"61","author":"Weber","year":"2022","journal-title":"Eur. J. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100482","DOI":"10.1016\/j.advnut.2025.100482","article-title":"Educational Attainment as a Super Determinant of Diet Quality and Dietary Inequities","volume":"16","author":"Olstad","year":"2025","journal-title":"Adv. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1093\/aje\/kwu148","article-title":"Inverse association of plasma vanadium levels with newly diagnosed type 2 diabetes in a Chinese population","volume":"180","author":"Wang","year":"2014","journal-title":"Am. J. Epidemiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"119252","DOI":"10.1016\/j.ecoenv.2025.119252","article-title":"Interactions between multiple serum metals and genetic variants for type 2 diabetes risk: A prospective Chinese cohort study","volume":"306","author":"Shen","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/BF01075924","article-title":"Modulation of insulin action by vanadate: Evidence of a role for phosphotyrosine phosphatase activity to alter cellular signaling","volume":"153","author":"Fantus","year":"1995","journal-title":"Mol. Cell Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/BF01075918","article-title":"Peroxovanadium compounds: Biological actions and mechanism of insulin-mimesis","volume":"153","author":"Bevan","year":"1995","journal-title":"Mol. Cell Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Xiong, Z., Xing, C., Xu, T., Yang, Y., Liu, G., Hu, G., Cao, H., Zhang, C., Guo, X., and Yang, F. (2021). Vanadium Induces Oxidative Stress and Mitochondrial Quality Control Disorder in the Heart of Ducks. Front. Vet. Sci., 8.","DOI":"10.3389\/fvets.2021.756534"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1080\/15287394.2019.1603280","article-title":"Estimates of urinary blood lead clearance and its relationship to glomerular filtration rate based on a large population survey","volume":"82","author":"Diamond","year":"2019","journal-title":"J. Toxicol. Environ. Health Part A"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"49063","DOI":"10.1007\/s11356-021-13623-0","article-title":"Blood lead, nutrient intake, and renal function among type 2 diabetic patients","volume":"28","author":"Chen","year":"2021","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"141357","DOI":"10.1016\/j.jhazmat.2026.141357","article-title":"The influence of sociodemographic factors on blood lead levels in healthy adults living in Belgrade, Serbia","volume":"504","author":"Bulat","year":"2026","journal-title":"J. Hazard. Mater."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1289\/ehp.7917","article-title":"A critical review of biomarkers used for monitoring human exposure to lead: Advantages, limitations, and future needs","volume":"113","author":"Barbosa","year":"2005","journal-title":"Environ. Health Perspect."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"116470","DOI":"10.1016\/j.ecoenv.2024.116470","article-title":"Association of serum metal levels with type 2 diabetes: A prospective cohort and mediating effects of metabolites analysis in Chinese population","volume":"279","author":"Liu","year":"2024","journal-title":"Ecotoxicol. Environ. Saf."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/18\/3068\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:58:20Z","timestamp":1789995500000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/18\/3068"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,20]]},"references-count":37,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["nu18183068"],"URL":"https:\/\/doi.org\/10.3390\/nu18183068","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,20]]}}}