Analysis of Metabolic and Inflammatory Biomarkers and Urinary Tungsten Concentrations in Human Serum Samples from the San Luis Valley Diabetes Study

Details

• Personal Author:
  McVeigh, Charlotte M. ; Josey, K. ; Tjung, J. A. ; Stoll, N. ; James, Katherine A. ; Bolt, Alicia M.
• Description:
  Background and Purpose: Tungsten is classified as an emerging environmental toxicant due to increased human exposure and lack of knowledge of the health risks. Epidemiological and in vivo studies have shown that tungsten exposure is associated with increased incidence and/or severity of cardiometabolic diseases including cardiovascular disease (CVD), chronic kidney disease (CKD), and diabetes, as well as enhanced cancer progression, however there is not a clear understanding of the underlying molecular mechanisms. An epidemiological cohort exposed to increased levels of tungsten is the San Luis Valley Diabetes Study. The San Luis Valley houses the headwaters of the Rio Grande River and has been experiencing regional water insecurity. The water demands in this region are also starting to trend higher than the current supply, putting this population at increased risk of exposure to environmental metals. Previous publications have correlated urinary tungsten concentrations with increased/ more severe diabetes and CKD outcomes in this cohort. One factor that can drive metabolic diseases is adipocyte dysfunction leading to a pro-inflammatory state. In vivo studies conducted by our lab have also shown that tungsten enhances adipogenesis in the bone marrow niche of mice. By looking at pro-inflammatory adipokines/ cytokines in the serum, we aim to draw further conclusions and provide some of the first evidence linking tungsten exposure to adipocyte dysfunction that could play a role in disease pathogenesis including diabetes, CKD, CVD, and cancer. Methods: Utilizing human serum samples from the San Luis Valley Diabetes Study, we conducted a multi-analyte enzyme-linked immunosorbent assays using the multi-plex Luminex platform. Human serum samples were analyzed for adipokine/ pro-inflammatory cytokines as well as several disease biomarkers. The analytes analyzed included: FABP4, Insulin, Leptin, Chemerin, OPN, Adiponectin, Adipsin, Resistin, PAI-1, IL-6, IL-1β, TNFa, MCP-1, IL-8, IL-18, VCAM-1, ICAM-1, VEGF-A, TFF3, MMP-9, MMP-1, CRP, Cystatin C, β 2-Microglobulin, Calbindin D, and NGF. Simple linear regression and Pearson Correlation analyses were used to correlate urinary tungsten concentration with analyte concentrations in the serum. Results: N=160 serum samples were analyzed in this study, correlating urinary tungsten values to the values (in pg/mL) of each analyte in the serum. Interestingly, there was a significant positive correlation between increasing urinary tungsten concentrations with increasing levels of analytes MMP-1, p = 0.0004; OPN, p = 0.0448; and VCAM-1, p = 0.0644. And a slight negative correlation between increasing urinary tungsten concentrations with decreasing levels of analytes FABP4, p = 0.0565 and Chemerin, p = 0.0818. Conclusions: Overall, this is the first study to correlate tungsten exposure to levels of adipokines/pro-inflammatory cytokines within the serum of humans. This is promising early data to suggest that tungsten exposure could be leading to adipocyte dysfunction. Since epidemiological studies are limited, further studying vulnerable populations such as this one is highly important to be able to determine molecular drivers of tungsten-mediated disease. Further studies need to be completed to include other demographic information into the analysis including sex, age, disease state, etc. In addition, we plan to statistically evaluate the impact of these adipokines/cytokines on the associations between tungsten and cardiometabolic and kidney disease outcomes in this cohort. Description provided by NIOSH
• Subjects:
  • Diabetes Mellitus
  • Immune System
  • Metabolism
  • Occupational Health
  • Safety
  • Tungsten
• Keywords:
  • Diabetes; Tungsten; Biomarkers; Metabolic disorders; Cohort studies; Immune reaction
• Source:
  Toxicologist 2025 Mar; 204(S1):609
• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  Colorado ; Dallas Region OSHA ; Denver Region OSHA ; New Mexico
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  2 pdf pages
• Volume:
  204
• NIOSHTIC Number:
  nn:20071597
• CAS Registry Number:
  • Tungsten (CAS RN 7440-33-7)
• Federal Fiscal Year:
  2025
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of New Mexico Health Sciences Center
• Peer Reviewed:
  False
• Start Date:
  20240901
• End Date:
  20260831
• Download URL:
  https://stacks.cdc.gov/view/cdc/259372/cdc_259372_DS1.pdf
• File Type:
  [PDF - 259.67 KB]
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ba3cb0b8d62754e4911fef2af28898020f8564ed399bdf4c10f04f8ac10999fb2d7741c5a44ea502d82cb17972fd02fe8000b2607bc3b365e27b6ca168921dfe