The independent and combined effects of blood heavy metal concentrations on all-cause mortality and cardiovascular mortality in adult patients with diabetes mellitus

Abstract

Background: Most epidemiological studies have focused on the association between single metal exposure and cardiovascular disease risk, utilizing a single-pollutant model for analysis. However, multiple metals may interact with each other, leading to misjudgment of health risks. This study sought to ascertain both the independent and combined effects of various blood heavy metal concentrations on all-cause mortality and cardiovascular mortality in patients with DM.

Methods: Patients (≥20 years) with DM from the NHANES (2011-2018) were selected. To explore the relationships of exposure to individual metals, including cadmium (Cd), mercury (Hg), manganese (Mn), lead (Pb), and selenium (Se), with all-cause mortality and cardiovascular mortality, weighted logistic regression and RCS analysis were leveraged. The WQS model was utilized to estimate the effects of combined blood metal exposures.

Results: 1,798 patients with DM were included. In the unadjusted model, ln-transformed blood Pb level (OR = 2.3, 95% CI: 1.70-3.10, p < 0.001) and ln-transformed Cd level (OR = 1.54, 95% CI: 1.27-1.87, p < 0.001) demonstrated positive associations with the all-cause mortality risk. According to RCS analysis, a nonlinear dose-response relationship was noted between Pb, Cd, Se, and the all-cause mortality risk (p-nonlinear < 0.05), while Hg and Mn showed linear relationships (p-nonlinear > 0.05).

Conclusion: According to this study, a high blood concentration of a combination of heavy metals is a significant risk factor for both cardiovascular disease and all-cause mortality of patients with diabetes, with Pb contributing a relatively higher proportion to these risks.

Keywords: all-cause mortality; cardiovascular mortality; diabetes mellitus; environmental health; heavy metals in blood.

Figure 1

Correlations among five metals in blood.

Figure 2

Dose–response effect between blood heavy metal content and all-cause death risk of diabetic patients. (A) The dose–response relationship between the lead content in blood and the risk of all-cause death in diabetic patients (fully adjusted RCS model). The baseline value (β = 1) is represented by a dotted line, and the inflection point appears at 0.120 (blood lead content after logarithmic conversion). (B) the relationship between the cadmium content in blood and the risk of all-cause death of diabetic patients (fully adjusted RCS model), the baseline value (β = 1) is represented by a dotted line, and the inflection point appears at −1.118 (logarithmic converted blood cadmium content) (C) the relationship between the mercury content in blood and the risk of all-cause death of diabetic patients is linear (fully adjusted RCS model). (D) The dose–response relationship between the blood selenium content and the risk of all-cause death of diabetic patients (fully adjusted RCS model), the baseline value (β = 1) is represented by a dotted line, and the inflection point appears at 5.265 (blood selenium content after logarithmic conversion). (E) The dose–response relationship between the manganese content in blood and the risk of all-cause death in diabetic patients (fully adjusted RCS model). The baseline value (β = 1) is indicated by the dotted line, and the inflection point appears at 2.211 (logarithmic converted blood manganese content). The adjustment of the model takes into account the following variables: age, gender, race, education level, exercise, smoking status, BMI, family PIR, drinking status, education level, direct high-density lipoprotein cholesterol, hyperlipidemia and hypert.

Figure 3

Dose–response effect between blood heavy metal content and risk of all-cause death in diabetic patients. (A) There is a linear relationship between the lead content in blood and the risk of all-cause death in diabetic patients (fully adjusted RCS model). (B) There is a linear relationship between the concentration of cadmium in blood and the risk of all-cause death in diabetic patients (fully adjusted RCS model). (C) There is a linear relationship between the content of mercury in blood and the dose–response between the content and the risk of all-cause death in diabetic patients (fully adjusted RCS model). (D) There is a linear relationship between the selenium content in blood and the risk of all-cause death in diabetic patients (fully adjusted RCS model). (E) There is a linear relationship between the manganese content in blood and the risk of all-cause death in diabetic patients (fully adjusted RCS model). The adjustment of the model takes into account the following variables: age, gender, race, education level, exercise, smoking status, BMI, family PIR, drinking status, education level, direct high-density lipoprotein cholesterol, hyperlipidemia and hypertension.

Figure 4

Relationship between WQS index of blood heavy metal mixture and risk of all-cause death in diabetic patients. Lbxpb-lead; Lxbcd-cadmium; LBXBMN- manganese; Lxbse-selenium; Lbxhg-mercury. The adjustment of the whole model takes into account the following variables: age, gender, race, education level, exercise, smoking status, BMI, family PIR, drinking status, education level and direct high density lipoprotein. Cholesterol, hyperlipidemia and hypertension.

Figure 5

Relationship between WQS index of blood heavy metal mixture and death risk of cardiovascular and cerebrovascular diseases in diabetic patients. Lbxpb-lead; Lxbcd-cadmium; LBXBMN- manganese; Lxbse-selenium; Lbxhg-mercury. The adjustment of the whole model takes into account the following variables: age, gender, race, education level, exercise, smoking status, BMI, family PIR, drinking status, education level, straight. High density lipoprotein cholesterol, hyperlipidemia and hypertension.