This study examined the association between hyperuricemia and metabolic syndrome, and the association between blood lead and serum uric acid concentrations. Hyperuricemia showed a significant association with metabolic syndrome even in the results adjusted for confounding variables, whereas lead was shown to be associated with hyperuricemia even at low blood concentrations.
According to existing studies
[13, 14], an increase in serum uric acid concentration is thought to partially contribute to an increase in blood pressure via the activation of the renin-angiotensin-aldosterone system by inducing renal vascular inflammation, preglomerular arteriolopathy, tubulointerstitial inflammation and fibrosis. Serum uric acid concentration also seems to interfere with blood vessel expansion by decreasing the response of blood vessels to acetylcholine and to increase blood pressure by causing endothelial dysfunction through interference in the excretion process of nitric oxide (NO) from vascular endothelial cells by expressing toxicity directly on the blood vessels
[15, 16]. In this regard, a study reported that when the activity of xanthine oxidase, which is involved in the uric acid generation process, was inhibited by administering allopurinol to patients, blood flow was improved along with vasodilation
Whether serum uric acid level independently influences the increase in blood glucose level is controversial. While there are reports on increased insulin resistance due to certain serum uric acid levels increasing blood flow and causing vasodilation to interfere with the action of nitric oxide, which facilitates glucose absorption
, other results suggest that hyperuricemia is caused by hyperinsulinemia due to insulin resistance acting on the renal tubules to facilitate the reabsorption of uric acid
[19, 20]. These results suggest an interaction between uric acid and insulin levels. However, the mean fasting glucose level in the hyperuricemia group was significantly lower than that in the healthy group in this study, contradicting the results of existing studies. Upon considering the results of recent related studies, a decreased fasting glucose level in patients with hyperuricemia is possibly due to the increase in uric acid excretion caused by the glomerular hyperfiltration when hyperglycemia is maintained
[21, 22]. However, additional research is necessary in the future to validate this hypothesis.
The effects of serum uric acid level on dyslipidemia have not yet been clearly identified; however, according to recent studies, the increase in uric acid concentration seems to reduce the function of lipid peroxidase and lipoprotein lipase, which are involved in lipolysis, while the process of decreased nitric oxide excretion from blood vessels is believed to affect the progression of dyslipidemia
[23, 24]. In this study, the total cholesterol and LDL-cholesterol levels in the hyperuricemia group were not statistically significant, but the mean levels were still higher compared to those in the healthy group. Meanwhile, triglyceride levels were significantly higher in the hyperuricemia group, with significantly lower HDL-cholesterol levels, than in the healthy group. In particular, the levels of the triglycerides related to metabolic syndrome showed the greatest difference in mean values when compared with the other parameters, which seems to be due to the decreased function of the tricarboxylic acid cycle with the increased oxidative stress in the mitochondria of liver cells as the uric acid synthesis increased due to purine metabolism, resulting in slower triglyceride metabolism and an increase in lipogenesis
Regarding the association between obesity and serum uric acid concentration, it is known that obese individuals mostly consume meat, with high intake of purine, which results in an increase in uric acid concentration
, and hyperuricemia is caused by the facilitation of uric acid reabsorption in the renal tubules due to high insulin resistance. These results point to obesity as the cause of hyperuricemia
[27, 28]. However, based on the various correlations identified so far, such as the close association between insulin resistance and nitric oxide synthesis dysfunction in vascular endothelial cells and the claim that uric acid interferes with the nitric oxide excretion process
, the increase in the risk for fatty liver in proportion to the purine metabolism-induced uric acid synthesis triggered by the deterioration in mitochondria function in liver cells
, and the contribution of the reduced mitochondria functioning to the fat accumulation in muscles and liver in a study with a non-obese elderly population
, hyperuricemia itself seems to partially contribute to obesity. This finding warrants additional research in the future.
In this study, the hyperuricemia group showed a significantly higher mean blood lead concentration than that in the healthy group. The subjects’ geometric mean (standard deviation) blood lead concentration was approximately 3.4 (1.8) μg/dL, which was significantly lower than 25.0 μg/dL
, the blood lead concentration designated by the Centers for Disease Control and Prevention (CDC) as affecting the physiological health of adults, and even below the recommended upper limit level of 5.0 μg/dL for children in 2012
. However, in our univariate and multivariate regression analyses, the risk of hyperuricemia was shown to increase even at low blood lead concentrations between 2.61 and 4.50 μg/dL.
Uric acid is synthesized through the metabolism of purine, and humans are known to have a relatively high level of serum uric acid concentration compared with other mammals, as humans do not possess the enzyme for metabolizing uric acid
. Therefore, to maintain an appropriate level of serum uric acid, males need to excrete a daily volume of 600–700 mg of uric acid through the glomeruli, and proximal and distal tubules of the kidney; ascending loop; and collecting duct. If kidney functioning is reduced, the probability of hyperuricemia becomes relatively high
. Furthermore, in this study, serum creatinine level and hyperuricemia showed a positive association, which is consistent with the existing study results that renal functioning affects serum uric acid levels.
In fact, according to recent studies, an increase in blood lead concentration caused a reduction in estimated glomerular filtration rate (eGFR) even at a blood lead concentration lower than 10.0 μg/dL
. In addition to the glomeruli, blood lead causes the atrophy and hyperplasia of the tubular epithelial cells and increases the risk for hyperuricemia by reducing secretory functions to cause interstitial fibrosis and inflammation
[7, 35, 36]. In addition, when blood lead concentration is higher than 1.2 μg/dL, the risk for gout reportedly increases with the reduction in uric acid excretion ability of the kidney
An independent association with hyperuricemia was observed for smoking and γ-GTP level; however, it is too early to assume that both are direct risk factors for hyperuricemia, as existing studies report inconsistent results, suggesting the need to conduct a prospective study
The steelmaking company investigated in this study was an independent steelmaker largely divided into steelmaking and rolling processes. The steelmaking process exposes workers to lead fumes during the dissolving process, during which metal containing impurities is melted
. In fact, according to a study that measured ambient lead concentration using individual samples during the steelmaking process, most of the samples showed lead concentrations exceeding 50% of the domestic threshold (0.05 mg/m3), indicating that the steelmaking process require attention regarding occupational lead exposure, along with the iron making process, in which metal is extracted by dissolving ore
[41–43]. In addition, the workers involved in iron-making processes were exposed to mineral dust, noise, hyperthermia, sulfur dioxide (SO2), carbon monoxide (CO), and hydrogen sulfide (H2S), but none of the causative factors of hyperuricemia identified by previous studies was found.
This study has its significance in providing results that controlled task properties and sex by limiting the subjects to male workers from a steelmaking company known to have the most number of lead handling processes among other metal industries, in comparison with existing studies that did not match task properties while targeting the general public or workers as subjects. It is also significant in that its simultaneous analyses revealed that hyperuricemia is significantly associated with metabolic syndrome and that low levels of blood lead can affect hyperuricemia.
This study has the following limitations: First, it is a cross-sectional study, and a causal relationship between blood lead level, serum uric acid level, and metabolic syndrome could not be established while attempting to explain the intervariable relationships using various studies in the existing literature. Second, recall bias might have existed, as the smoking, drinking, and exercise habits, and drug therapy were examined through surveys; this bias was minimized through the comparison between existing survey data for identical subjects. Third, no survey was conducted on diet related to serum uric acid concentration; it was partially controlled as the workers took the same meal twice a day at the company canteen while working 3 shifts, but a more accurate investigation needs to be conducted. Lastly, as it is an analysis for a particular group, our study was limited in generalizing the results to all population groups. In a group without occupational exposure, identical physiological mechanisms due to blood lead levels were reported
. However, a study with a general population group is needed in the future.
At present, with the prevention and management of workplace workers’ cerebrovascular and cardiovascular diseases becoming increasingly important, attention should be given to serum uric acid concentration, which has been regarded as a causal factor only for gout. In particular, from the perspective of occupational environment medicine, hyperuricemia should be managed in individuals who are likely to be exposed to lead over a longer period of time for occupational and environmental reasons. The results of this study suggest that a risk for hyperuricemia exists even at low blood lead concentrations. Thus, it is necessary to conduct a large-scale prospective study to identify any causal relationship.