# Perfluoroalkyl substances and incident type 2 diabetes in a multi-ethnic population: A metabolome-genome investigation

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $645,869

## Abstract

PROJECT SUMMARY
Increasing prevalence of type 2 diabetes (T2D) is accompanied by racial/ethnic disparities, but etiological factors
promoting the T2D epidemic and T2D disparities are not fully understood. Growing experimental evidence shows
that exposures to endocrine-disrupting chemicals (EDCs), such as per- and polyfluoroalkyl substances (PFAS),
promote T2D development, likely in synergy with known risk factors such as genetic variations. PFAS are
ubiquitous and persistent chemicals that perturb metabolism. However, few prospective studies examined the
association between PFAS and T2D risk, and those were almost exclusively in White populations. Previous
studies also lacked clinically ascertained T2D diagnosis, investigated only a few of the many potentially
hazardous PFAS, and did not examine potential effects of PFAS mixtures or gene–PFAS interactions. State-of-
the-art integrated omics approaches can overcome these barriers to advance the field. We propose the first
integrated metabolome–genome approach to (1) characterize the associations between PFAS concentrations
(individual PFAS and mixtures) in prediagnostic plasma samples and incident T2D risk and potential effect
modification by genetic predisposition to T2D using polygenic risk scores as an innovative solution for studying
interactions, (2) identify underlying dysregulated metabolic pathways, and (3) identify metabolic signatures in
prediagnostic plasma samples defined by EDC exposures and endogenous metabolites associated with T2D
risk. We will perform a nested case–control study leveraging BioMe, an ongoing electronic health record-linked
biobank with >55,000 participants enrolled while seeking primary care at Mount Sinai Hospital (NY) since 2007.
Incident T2D cases are matched (1:1) to BioMe T2D-free controls (N = 1,700) and are of African American,
Hispanic and White ancestry, with ~6 years average time between blood draw and T2D diagnosis. We will use
prediagnostic plasma to measure PFAS and metabolic pathways using state-of-the-art high-resolution
metabolomics (HRM) approaches. We will replicate findings among incident T2D cases and matched controls
from the population-based Multiethnic Cohort (MEC) study in Los Angeles and Hawaii with extant genome data
and prediagnostic plasma concentrations of PFAS and HRM measured at the same lab as BioMe samples. In
contrast to prior studies, we incorporate a wide suite of legacy and emerging PFAS, exposure-mixture effects,
and gene–environment interactions by leveraging state-of-the-art metabolome–genome approaches and a
rigorous discovery–replication design in two unique, well-phenotyped multiethnic cohorts with prediagnostic
plasma samples to identify early biomarkers associated with T2D. This research relies on a multidisciplinary
team of seasoned investigators with expertise in environmental/genetic epidemiology, PFAS and T2D research,
and state-of-the-art HRM, genomics, and biostatistical exposure–mixture methods. Findings will info...

## Key facts

- **NIH application ID:** 10862866
- **Project number:** 5R01ES033688-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Damaskini Valvi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $645,869
- **Award type:** 5
- **Project period:** 2022-09-02 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862866

## Citation

> US National Institutes of Health, RePORTER application 10862866, Perfluoroalkyl substances and incident type 2 diabetes in a multi-ethnic population: A metabolome-genome investigation (5R01ES033688-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10862866. Licensed CC0.

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