# In utero exposure to diabetes and future cardiometabolic risk: the role of miRNA

> **NIH NIH K23** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2021 · $19,964

## Abstract

Abstract
 The candidate, Jeanie B. Tryggestad, MD, proposes a Mentored Patient-Oriented Research Career
Development Award project as a mechanism by which to achieve her ultimate career goal of becoming a
physician scientist studying type 2 diabetes and its comorbidities in children, specifically the cardiometabolic
effects that emerge in childhood before overt disease. Perinatal conditions like diabetes mellitus (DM) have
been shown to “program” offspring for certain metabolic phenotypes later in life. For example, children born to
diabetic mothers have been shown to have increased adiposity at birth that can persist through childhood and
increase the risk of cardiovascular disease and type 2 diabetes (T2DM) in early adulthood. The mechanisms
underpinning this sequence are not well understood, but epigenetic modification has come to the forefront as a
potential mediator of the association between perinatal conditions and future cardiometabolic disease. Dr.
Tryggestad postulates that altered miRNA expression is an important mechanism by which maternal DM elicits
changes that influence cardiometabolic health in the children. She hypothesizes that the diabetic milieu
induces changes in fetal endothelial cell miRNA that target specific mRNAs within the endothelial cell and
result in miRNA release into the circulation, allowing the miRNA to act on distant tissues. This hypothesis will
be tested with the following specific aims: 1) to determine the mechanisms of action of miRNAs 148a and 126
in HUVEC and 2) to examine the abundance of miRNAs 148a and 126 in vivo and in vitro and their impact on
distant cells. She will identify target proteins of two miRNAs that are upregulated in endothelial cells of infants
of diabetic mothers and assess the impact of these miRNAs on endothelial function. The effect of the miRNAs
on distant tissues will also be studied. In the long term, the findings will provide an understanding of the
molecular and cellular processes that are altered by the diabetic milieu and result in cardiometabolic
complications, including obesity and diabetes, in the offspring of women with diabetes. Further, this work may
help us to develop new prevention and treatment strategies.
 Dr. Tryggestad has demonstrated a commitment to improving children's health through her research in
childhood obesity and diabetes. Her research has focused on the cardiometabolic effects of obesity and
diabetes on children. Her previous work, funded by Endocrine Fellows Foundation, Pediatric Endocrine
Society, and Oklahoma Shared Clinical and Translational Resources Pilot Grant, has resulted in five first-
author papers. Dr. Tryggestad is presently an assistant professor at the University of Oklahoma Health
Sciences Center in the Department of Pediatrics, Section of Diabetes/Endocrinology.
 This proposal expands Dr. Tryggestad's research in the cardiometabolic effects of obesity and diabetes.
However, training gaps have been identified regarding an in-depth knowled...

## Key facts

- **NIH application ID:** 10426687
- **Project number:** 3K23DK106533-04S1
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Jeanie Beatrice Tryggestad
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $19,964
- **Award type:** 3
- **Project period:** 2016-09-12 → 2021-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10426687

## Citation

> US National Institutes of Health, RePORTER application 10426687, In utero exposure to diabetes and future cardiometabolic risk: the role of miRNA (3K23DK106533-04S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10426687. Licensed CC0.

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