# Understanding and Targeting the Pathophysiology of Youth-onset Type 2 Diabetes-Texas Children's Center.

> **NIH NIH U01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $715,946

## Abstract

Project Summary
Youth-onset type 2 diabetes (T2D) is a heterogeneous disease, more rapidly progressive than adult-onset
disease, and is associated with increased comorbidities. Yet, it is not clear which high-risk youth will eventually
progress to T2D. T2D pathogenesis is related to complex hormonal mechanisms that result in β-cell dysfunction,
influenced by genetic, epigenetic, social and environmental factors. The overarching goal of this proposal is to
prevent youth-onset T2D. Our aims are to identify the risk factors and pathophysiologic changes that lead to the
development of youth-onset T2D. We will collaborate as a member of a consortium of clinical centers to achieve
these aims. We will leverage our community and stakeholders’ engagement, our robust research infrastructure
and the diverse high-risk patient population at our Center, to recruit a high-risk diverse cohort of children from
early through mid-puberty (age range 8 to 14 years, Tanner stage II-IV at enrollment), with normal glucose
tolerance and with prediabetes. We will screen 300 children aiming to retain 200 children longitudinally, perform
in-depth assessments and survey them for the progression to T2D. We will investigate complementary pathways
which, by disrupting the delicate balance between insulin sensitivity and secretion, are most likely to modulate
the risk of progression to T2D in youth. To that end, we will 1) characterize the evolution of β-cell dysfunction in
relation to changes in adiposity, sex steroids and growth factors during the pubertal transition. We will combine
clinical phenotypes with physiologic measures of glucose tolerance, β-cell function and insulin sensitivity (derived
from serial oral glucose tolerance tests), circulating metabolites, body composition and abdominal fat changes
(dual-energy X-ray absorptiometry and magnetic resonance imaging); 2) employ novel epigenetic markers of
DNA methylation at correlated regions of systemic interindividual variation (CoRSIVs) to evaluate epigenetic
changes that may predispose to β-cell dysfunction; and 3) evaluate social and behavioral determinants of health
that could lead to long-term disease phenotype through promotion of adiposity and activation of the
hypothalamic-pituitary-adrenal axis (as measured by urinary catecholamines and cortisol), and inflammation
pathways. Our innovative study design will allow us to determine the evolution of the risk factors for youth-onset
T2D during the pubertal transition, the underlying metabolic changes, and the modifying social and
environmental effects, in the context of genetic/epigenetic susceptibility. The findings from this study are highly
significant to improve the identification of high-risk children vulnerable to progression to T2D, and characterize
the pathophysiology of the disease during a critical window of childhood growth and development. The
knowledge gained will allow the consortium to develop risk stratification algorithms and design personalized
prec...

## Key facts

- **NIH application ID:** 10800694
- **Project number:** 5U01DK134982-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** FIDA BACHA
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $715,946
- **Award type:** 5
- **Project period:** 2023-03-05 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10800694

## Citation

> US National Institutes of Health, RePORTER application 10800694, Understanding and Targeting the Pathophysiology of Youth-onset Type 2 Diabetes-Texas Children's Center. (5U01DK134982-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10800694. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*