A nested case-control study of serum zinc and incident diabetes among Chinese adults: Effect modifications and mediation analysis

Although numerous evidences suggest that zinc may have a beneficial impact on preventing and treating diabetes, findings from the population studies are inconclusive. To address this gap, we conducted a nested case-control study, employing restricted cubic splines and a conditional logistic regression model to explore the association between serum zinc levels and the risk of diabetes. We also assessed potential effect modifications through stratified analyses and examined the mediating effects of metabolic indicators using a multiclass mediation effect model. We measured baseline serum zinc concentrations using Inductively Coupled Plasma Mass Spectrometry in a cohort of 2156 participants, including 1078 individuals with diabetes and 1078 matched controls. Our findings revealed a 51 % increased risk of diabetes when comparing the highest quartile (Q4) to the lowest quartile (Q1) of serum zinc levels (Odds Ratio [95 % Confidence Interval]: 1.51 [1.09, 2.09]). There was a positive linear dose-response relationship between serum zinc and diabetes risk (P overall ≤0.01, P nonlinear = 0.20). Effect modifications were evident between serum zinc and factors such as educational attainment, body mass index, alcohol index, family history of diabetes, history of hypertension, coronary heart disease, and stroke, all of which influenced the risk of diabetes (all P-interaction <0.05). Moreover, our study identified significant indirect effects of triglycerides levels on diabetes risk for participants in the third (Q3) and fourth (Q4) quartiles of serum zinc, with mediation proportions of 19.23 % and 19.28 %, respectively. A significant indirect effect of alanine aminotransferase on diabetes risk was found for those in the Q4 of serum zinc, with a mediation proportion of 12.05 %. Considering these findings, it is advisable to conduct testing for serum zinc level and exercise caution when considering zinc supplementation. Furthermore, our results emphasized the necessity for additional validation through large-sample prospective population studies and experimental research.