# A nested case-control study of exposure to toxic metals, essential metals and their interaction on the risk of type 2 diabetes

> **NIH NIH R01** · BROWN UNIVERSITY · 2020 · $525,145

## Abstract

PROJECT SUMMARY
Type 2 diabetes (T2D) is an epidemic of our time afflicting more than 400 million people globally. Identification
of novel preventable risk factors is urgent because established risk factors do not fully account for the rapid
increase in T2D rates. The etiologic role of heavy metals in T2D risk has gained considerable attention
worldwide. In the U.S., the National Toxicological Program recently recommended further research on this
topic following a comprehensively review of the relationship between environmental factors and T2D. Recent
data linking heavy metals to T2D risk, while tantalizing, come mainly from cross-sectional studies susceptible
to reverse causation. Moreover, few studies have investigated the role of exposures to multiple metals on T2D
risk, such that there is little evidence of the independent and joint effects of multiple metals. Separately,
essential metals are recommended as beneficial supplements to mitigate the diabetic effects of toxic metals,
but the optimal levels of essential metals required to counteract the toxic metal effects are not well understood.
Thus, large and high-quality prospective studies are urgently needed to further investigate heavy metals as risk
factors for T2D, and the possible mitigating role of essential metals. Our research team, with support from NIH,
has built the population-based prospective Jinchang Metal Cohort Study. This on-going study includes in-
person interviews of 42,122 participants in 2011-13, a first follow-up visit in 2014-16, and a second follow-up
visit started in 2017. At the baseline and subsequent visits, subjects completed 1) physical examinations; 2)
clinical laboratory tests; 3) in-person interviews; and 4) collections of blood and urine samples. Extensive pilot
work on T2D risk associated with metal exposure has already been conducted in this population. With such
extensive data available from this large prospective population-based cohort, we are now in a unique position
to conduct a nested case-control study to comprehensively investigate if heavy metal exposures increase T2D
risk. Baseline serum and urine levels of selected heavy metals will be measured from 2,200 incident T2D
cases and their individually age-sex-matched 2,200 controls who were T2D- and prediabetes-free at the time
when the corresponding cases were diagnosed with T2D. The study specific aims include: 1) Determine
whether baseline toxic metal levels are independently or jointly associated with T2D risk; 2) Determine whether
imbalanced baseline levels (deficiency or overexposure) of essential metals are independently or jointly
associated with T2D risk; and 3) Determine whether diabetic effects of toxic metals can be mitigated by
essential metals and, if so, the optimal body levels of essential metals that could reduce T2D risk from toxic
metals. The Jinchang Metal Cohort Study is the only large prospectively study specifically designed to
investigate the impact of metal exposures on cardi...

## Key facts

- **NIH application ID:** 9892009
- **Project number:** 5R01ES029082-02
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Simin Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $525,145
- **Award type:** 5
- **Project period:** 2019-03-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892009

## Citation

> US National Institutes of Health, RePORTER application 9892009, A nested case-control study of exposure to toxic metals, essential metals and their interaction on the risk of type 2 diabetes (5R01ES029082-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9892009. Licensed CC0.

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