Association of metabolic syndrome and sarcopenia with all-cause and cardiovascular mortality: a prospective cohort study based on the NHANES.

Background: Metabolic syndrome (MetS) and sarcopenia (SP) have emerged as significant public health concerns in contemporary societies, characterized by shared pathophysiological mechanisms and interrelatedness, leading to profound health implications. In this prospective cohort study conducted within a US population, we aimed to examine the influence of MetS and SP on all-cause and cardiovascular mortality. Methods: This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) III for the years 1999-2006 and 2011-2018, and death outcomes were ascertained by linkage to National Death Index (NDI) records through December 31, 2019. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause and cardiovascular mortality. In addition, subgroup and sensitivity analyses were conducted to test the robustness of the results. Results: Over a median follow-up period of 13.3 years (95% CI: 12.8-13.8), 1714 deaths were observed. The groups characterized by MetS-/SP+, MetS+/SP-, and MetS+/SP+ exhibited higher all-cause mortality rates in comparison to the MetS-/SP- group, with the MetS+/SP+ group (HR 1.76, 95% CI: 1.37-2.25) displaying the highest all-cause mortality. Increased cardiovascular mortality was observed in the MetS+/SP- (HR 1.84, 95% CI: 1.24-2.72), and MetS+/SP+ groups (HR 2.39, 95% CI: 1.32-4.35) compared to the MetS-/SP- group, whereas it was not statistically significant in the MetS-/SP+ group. However, among males and individuals aged < 60, the presence of both MetS and SP (MetS+/SP+ group) was found to be significantly associated with a higher risk of all-cause and cardiovascular mortality. Conclusion: The coexistence of MetS and SP increased the risk of all-cause and cardiovascular mortality, particularly in males and in nonelderly populations. Individuals with either MetS or SP may require more careful management to prevent the development of other diseases and thereby reduce mortality.

Prevalence and risk factors of MAFLD and its metabolic comorbidities in community-based adults in China: A cross-sectional study.

AIMS: There is a growing interest in the co-management of metabolic dysfunction-associated fatty liver disease (MAFLD) and its metabolic comorbidities. However, there is insufficient epidemiological data regarding MAFLD and its metabolic comorbidities in China. This study aims to investigate the prevalence and risk factors of MAFLD and its metabolic comorbidities. METHODS: 9171 participants were recruited in this cross-sectional study, utilizing a multistage, stratified sampling method. All participants underwent a comprehensive assessment. The diagnosis of MAFLD was based on vibration-controlled transient elastography (VCTE). The prevalence of MAFLD and its metabolic comorbidities was calculated. Binary and ordinary logistic regressions were conducted. RESULTS: The overall weighted prevalence of MAFLD was 21.18%. Of the 2081 adults with MAFLD, 1866 (89.67%) had more than one metabolic comorbidity, and only 215 (10.33%) did not have comorbidity. Among the population with MAFLD, the prevalence of dyslipidemia, hypertension, hyperuricemia, and diabetes was 67.47%, 43.73%, 39.10%, and 33.88%, respectively. Advanced age, male gender, overweight/obesity, excessive alcohol consumption, and elevated HOMA-IR levels were positively correlated with the number of MAFLD-related metabolic comorbidities. CONCLUSIONS: A significant proportion of individuals diagnosed with MAFLD presented with metabolic comorbidities. Therefore, engaging in the co-management of MAFLD and its metabolic comorbidities is imperative.

Association of sensitivity to thyroid hormones with all-cause mortality in euthyroid US adults: A nationwide cohort study.

Background This study aimed to examine the associations of thyroid hormone sensitivity indices, including free triiodothyronine to free thyroxine (FT3/FT4) ratio, thyroid feedback quantile-based index by FT4 (TFQIFT4), thyroid-stimulating hormone index (TSHI), and thyrotrophic thyroxine resistance index (TT4RI) with all-cause mortality in euthyroid adults. Methods The study included 6243 euthyroid adults from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. FT3/FT4 ratio, TFQIFT4, TSHI, and TT4RI were calculated. The multivariable Cox proportional hazard regression, restricted cubic spline (RCS), and subgroup analysis were conducted. Results Individuals in quartile 4th (Q4) had lower all-cause mortality than those in quartile 1st (Q1) of FT3/FT4 ratio (OR 0.70, 95% CI (0.51, 0.94)). Regarding TFQIFT4, individuals in Q4 of TFQIFT4 had a 43% higher all-cause mortality than those in Q1 (OR 1.43, 95% CI (1.05, 1.96)) (P <0.05, all). Compared with participants in Q1, no associations of TSHI and TT4RI with mortality were found. TFQIFT4 was linearly and positively associated with mortality. However, the FT3/FT4 ratio showed a U-shaped association with mortality. Conclusions Increased risk for all-cause mortality was positively associated with TFQIFT4, suggesting that increased risk for all-cause mortality was associated with decreased central sensitivity to thyroid hormones. Furthermore, the FT3/FT4 ratio showed a U-shaped association with mortality, with an inflection point at 0.5. However, more cohort studies are needed to validate the conclusions.

Sex-Specific Associations of Five Serum Essential Metal Elements with Thyroid Nodules in Euthyroid Adults: a Cross­sectional Study.

The association between the serum essential metal elements (magnesium, iron, copper, zinc, and calcium) and thyroid nodules is still inconsistent. The current study aims to investigate the relationship of metal elements with thyroid nodules and their malignant tendency. A total of 6480 Chinese euthyroid adults were included in our study. We collect basic information through questionnaires and medical checkups. We diagnose thyroid nodules by ultrasound and detect serum trace metal concentrations by using an automatic biochemical analyzer. Binary and multinomial logistic regressions were used to investigate the associations. As a result, we found that serum copper concentrations were positively associated with thyroid nodules in the second, third, and fourth quartiles, compared to the first quartile (P = 0.024, P = 0.016, P = 0.032) in women and P for trend is 0.038. There is a significant sex-specific association between copper concentrations and thyroid nodules (P for interaction = 0.009). The results of the multinomial logistic regression analyses indicate high serum calcium and magnesium concentrations emerged as consistent risk factors for thyroid nodules in both genders, whereas low zinc was a sex-specific factor. We also observed significant sex interactions in the relationships of magnesium (P for interaction = 0.043) with thyroid nodules with malignant tendency among participants with thyroid nodules. In conclusion, our study suggests that gender is an important factor when studying the association between serum metals and thyroid nodules. The imbalance of selected metal elements (calcium, copper, zinc, and magnesium) may relate to thyroid nodules and their malignant tendency, and future prospective studies are needed to further confirm the associations.

Associations between blood essential metal mixture and serum uric acid: a cross-sectional study.

Introduction: Although several studies have explored the associations between single essential metals and serum uric acid (SUA), the study about the essential metal mixture and the interactions of metals for hyperuricemia remains unclear. Methods: We performed a cross-sectional study to explore the association of the SUA levels with the blood essential metal mixture, including magnesium (Mg), calcium (Ca), iron (Fe), copper (Cu), zinc (Zn), manganese (Mn) in Chinese community-dwelling adults (n=1039). The multivariable linear regression, the weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were conducted to estimate the associations of blood essential metals with SUA levels and the BKMR model was also conducted to estimate the interactions of the essential metals on SUA. Results: In the multivariable linear regression, the association of blood Mg, Mn, and Cu with SUA was statistically significant, both in considering multiple metals and a single metal. In WQS regression [ß=13.59 (95%CI: 5.57, 21.60)] and BKMR models, a positive association was found between the mixture of essential metals in blood and SUA. Specifically, blood Mg and Cu showed a positive association with SUA, while blood Mn showed a negative association. Additionally, no interactions between individual metals on SUA were observed. Discussion: In conclusion, further attention should be paid to the relationship between the mixture of essential metals in blood and SUA. However, more studies are needed to confirm these findings.

Single and combined associations of blood lead and essential metals with serum lipid profiles in community-dwelling adults.

Background: Although several studies have examined the relationships between lead (Pb) exposure and serum lipid profiles, the associations of the metal mixture, including lead (Pb) and essential metals with lipid profiles, remain unclear. Objective: To investigate the associations of the metal mixture including Pb and essential metals [magnesium (Mg), manganese (Mn), copper (Cu), iron (Fe), zinc (Zn), and calcium (Ca)] with serum lipid profiles [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)], as well as the potential interactions among the metals. Methods: Nine hundred and ninety-eight Chinese community-dwelling adults completed a questionnaire and underwent checkups of anthropometric parameters, serum lipid profile levels (TC, TG, LDL-C, and HDL-C), and blood metal concentrations (Pb, Mg, Mn, Cu, Fe, Zn, and Ca). The multivariable linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were applied to evaluate the single and combined associations of blood Pb and essential metals with serum lipid profiles. Results: In the multivariable linear regression model, the blood Pb was positively associated with TC, LDL-C, and HDL-C (p < 0.05, all), and the blood Mg were positively associated with serum TC, LDL-C, and Ln TG (p < 0.05, all). In the WQS regression and BKMR models, the metal mixture of blood Pb and the essential metals was positively associated with all of the serum lipid profiles. In addition, an inverse U-shaped association of Pb with Ln TG and the positive interactive effect between blood Pb and Mg levels on TC and LDL-C were found. Conclusion: The levels of blood Pb, together with the essential metals, especially Mg levels, are suggested to be considered when assessing dyslipidemia risk. However, more evidence is still needed to validate the conclusions.

Association of multiple blood metals with thyroid function in general adults: A cross-sectional study.

Introduction: Thyroid function has a large impact on humans' metabolism and is affected by iodine levels, but there is a scarcity of studies that elucidate the association between thyroid function and other elements. Methods: We performed a cross-sectional study on 1,067 adults to evaluate the associations of the common essential metals with thyroid function in adults living in an iodine-adequate area of China. Serum free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH), and blood metals (zinc, iron, copper, magnesium, manganese, and calcium) were measured. Further, the thyroid hormone sensitivity indexes, FT3:FT4 ratio, and thyrotropin T4 resistance index (TT4RI) were calculated. Linear regression, quantile g-computation, and Bayesian kernel machine regression methods were used to explore the association of metals with thyroid function. Results: We found that the TSH levels correlated with copper (negative) and zinc (positive). Iron and copper were positively associated with FT3 and FT4 levels, respectively. Iron (positive) and copper (negative) were correlated with the FT3:FT4 ratio. Furthermore, we found that manganese was inversely correlated with TT4RI, while zinc was positively correlated. Discussion: Our findings suggest that manganese, iron, copper, and zinc levels were strongly correlated with thyroid function, and patients with thyroid disorders are recommended to measure those metals levels.

Central Sensitivity to Free Triiodothyronine With MAFLD and Its Progression to Liver Fibrosis in Euthyroid Adults.

CONTEXT: Impaired sensitivity to thyroid hormones has been demonstrated to be positively associated with the prevalence of metabolic disorders. However, the relationship between sensitivity to thyroid hormones and metabolic dysfunction-associated fatty liver disease (MAFLD) and liver fibrosis remained unclear. OBJECTIVE: We aimed to determine the associations of thyroid hormone sensitivity indices with MAFLD and its progression to liver fibrosis in Chinese euthyroid adults. METHODS: This community-based study included 7906 euthyroid adults. We calculated the thyroid sensitivity indices, including free triiodothyronine to free thyroxine (FT3/FT4) ratio, Thyroid Feedback Quantile-based Index by FT4 (TFQIFT4), and Thyroid Feedback Quantile-based Index by FT3 (TFQIFT3), indicating peripheral and central thyroid hormone sensitivity respectively. Liver steatosis and fibrosis were diagnosed by vibration-controlled transient elastography (VCTE). Multivariable logistic/linear regression and restricted cubic spline (RCS) analysis were conducted. RESULTS: Compared with participants in the first quartile (Q1), the prevalence of MAFLD was increased by 62% in the fourth quartile (Q4) of FT3/FT4 ratio (OR 1.62; 95% CI [1.38, 1.91]) and by 40% in Q4 of TFQIFT3 (OR 1.40; 95% CI [1.18, 1.65]) (both P < .05). No associations between TFQIFT4 and the prevalence of MAFLD were found. In addition, compared with participants in Q1, the prevalence of liver fibrosis was increased by 45% in Q4 of TFQIFT3 (OR 1.45; 95% CI [1.03, 2.06]) (P < .05) in participants with MAFLD. CONCLUSION: Impaired central sensitivity to FT3 was associated with MAFLD and its progression to liver fibrosis. More prospective and mechanism studies are warranted to confirm these conclusions.

Sex-specific associations of the urinary fourteen-metal mixture with NAFLD and liver fibrosis among US adults: A nationally representative study.

Although previous studies have examined the hepatotoxicity of single metal exposure, the associations between metal mixture and non-alcoholic fatty liver disease (NAFLD) or fibrosis remain unclear. This study investigated the associations of urinary metal mixture with the risks of NAFLD and liver fibrosis in US adults using data from the National Health and Nutrition Examination Survey (NHANES) from 2017.01 to 2020.03. Vibration-controlled transient elastography was used to detect the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), which are indicators of NAFLD and liver fibrosis respectively. Three novel mixture modeling approaches including the Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regression and quantile g-computation (qgcomp) were used to estimate the associations of the urinary fourteen-metal mixture with Ln CAP and Ln LSM. There were 2283 adults aged over 18 years (1209 women and 1074 men) were included. Among women, urinary metal mixture was positively associated with Ln CAP in the BKMR and qgcomp models (both P < 0.05). However, no significantly associations of urinary metal mixture with Ln CAP were observed among men in all models (all P > 0.05). The metal mixture was not associated with Ln LSM in the three models regardless of genders (all P > 0.05). In conclusion, we observed sex-specific associations between urinary metal mixture and the prevalence of NAFLD in US adults. These findings emphasize the role of environmental heavy metal exposure in the development of NAFLD, and confirm the need for more prospective cohort studies on sex-specific manner.