Serum Levels of 18 Trace Elements and Type 2 Diabetes Mellitus: A Propensity Score-Matched Case–Control Study in Northwest Chinese Adults

Objective: Current evidence on the association between multiple trace elements and type 2 diabetes mellitus (T2DM) remains limited, particularly regarding combined effects, nonlinear dose–response 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–matched case–control 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–response 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–response 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–response 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.