# What Activates Type 2 Diabetes in Children (WATCh)?

> **NIH NIH U01** · UNIVERSITY OF COLORADO DENVER · 2024 · $59,239

## Abstract

PROJECT SUMMARY
Obesity and subsequently type 2 diabetes (T2D) is increasingly common in adolescents, but the
phenotype of youth-onset T2D (YO-T2D) differs from adults. The NIDDK TODAY study we
helped lead, demonstrated that youth with T2D had a high (≈50%) and rapid failure rate on oral
medications and faster need for insulin therapy vs. adults treated for a similar duration in the
ADOPT study. As further evidence, in our NIDDK RISE study, where treatment responses in
youth with impaired glucose tolerance (IGT) or newly diagnosed T2D were directly compared to
adults of similar BMI and initial glycemia, youth were twice as insulin resistant as adults and had
rapid deterioration of β-cell function and glycemic control compared to adults given the same
treatment with similar medication adherence. Finally in our HIP study, metformin did not improve
insulin sensitivity or secretion even when started early in puberty in normoglycemic youth with
obesity, arguing for innovative approaches. Of most concern, TODAY demonstrated an
incidence of microvascular diabetes complications ranging from 32-68% by a mean age of only
26.4±2.8 yrs, affecting individuals who should be at their peak of productivity; complications
more heavily affected those with minority race/ethnicity, raising concerns related to health
disparities. This unprecedented early morbidity and projected health care costs mandate a focus
on defining a) the ideal T2D diagnostic and/or screening criteria for youth b) pathophysiologic
distinctions between Y-T2D and adult-onset T2D c) how to prevent Y-T2D d) how to better treat
Y-T2D once present. Though some risk factors for developing Y-T2D (e.g. family history,
obesity, etc.) are well-established, only a small subset of these high-risk youth progress to T2D
as adolescents. Thus, other causal components need to be explored, such as adverse
childhood experiences, stress, poverty, racism, sleep/circadian rhythm, subtle differences within
sedentary behavior, and the exact impact(s) of pubertal hormones. The 15-site multicenter
DISCOVERY Study aims to enroll 3,600 diverse youth (240 from our site) at risk for developing
T2D from urban and rural locations who are early in puberty, and perform longitudinal
assessments every 6 mo paired with additional sample storage to be analyzed once a “critical
mass” of youth with new-onset T2D is accumulated. Our primary objective is to identify
physiologic drivers and other determinants of progression to T2D by charting the course of
glycemia, β-cell function, insulin sensitivity, psychosocial, behavioral, and social determinants of
health during this critical period of maturation and inform approaches for precise prediction of
which youth are at highest risk of developing T2D during this period. Local and central
stakeholders will play an active role in the study and provide feedback during follow-up.
Secondarily, during this 5-year funding period, DISCOVERY will create a biobank of samples
with associated phenot...

## Key facts

- **NIH application ID:** 11000918
- **Project number:** 3U01DK134958-02S1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** MEGAN MORIARTY KELSEY
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $59,239
- **Award type:** 3
- **Project period:** 2023-03-10 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11000918

## Citation

> US National Institutes of Health, RePORTER application 11000918, What Activates Type 2 Diabetes in Children (WATCh)? (3U01DK134958-02S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/11000918. Licensed CC0.

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