# Genetic and Epidemiological Predictors of Glucose Homeostasis Measures

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2021 · $651,974

## Abstract

Summary
Insulin sensitivity and insulin secretion are traits that have a significant impact on the risk of type 2 diabetes
(T2D). The over-arching goal of this proposal is to understand the pathophysiology underlying variation of
these intermediate phenotypes in Mexican Americans, the largest US minority group and one at high risk of
T2D. The Genetics Underlying Diabetes in Hispanics (GUARDIAN) Consortium represents the largest effort to
identify the genetic determinants underlying diabetes-related intermediate phenotypes (DK085175). During the
previous funding period, genome-wide association studies (GWAS) focused on common genetic variation
identified four genome-wide significant loci underlying variation in glucose homeostasis traits which translated
to the clinical endpoint, T2D. In this application, we will build upon significant prior genetic findings with
integration of biological (metabolomics) and analytical (hierarchical clustering and interaction analysis)
approaches to further refine insulin resistance and insulin secretion phenotypes and explore their biological
basis. Aim 1 will develop a novel methodology using existing GWAS and metabolomics data to impute
genetically regulated metabolites (GReM) and test their association with measures of glucose homeostasis in
the GUARDIAN Consortium. Aim 2 will refine known and novel variants associated with T2D and related
phenotypes through hierarchical clustering and perform interaction analyses which exploit the bimodal nature
of T2D to identify additional insulin resistance loci. Aim 3 will identify genetic determinants of dynamic
measures of glucose homeostasis in diverse human populations and translate these loci to T2D. The unique
strengths of this proposal include detailed phenotypes for glucose homeostasis that have not been extensively
examined in the GWAS setting, a focus on the Mexican American population, and our long-standing, highly
productive collaborative team. This project has great public health significance as it is focused on increasing
our biological understanding and resultant mechanisms for the prevention of T2D using pre-diabetic measures
of glucose homeostasis.

## Key facts

- **NIH application ID:** 10088441
- **Project number:** 5R01DK118062-03
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Nicholette D. Allred
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $651,974
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10088441

## Citation

> US National Institutes of Health, RePORTER application 10088441, Genetic and Epidemiological Predictors of Glucose Homeostasis Measures (5R01DK118062-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10088441. Licensed CC0.

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