# Gestational diabetes and offspring aging and metabolism

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $247,547

## Abstract

The goal of this R21 application, “Gestational diabetes and offspring aging and metabolism,” is to examine
whether gestational diabetes mellitus (GDM) is linked to adverse offspring metabolism through accelerated
molecular aging. In the United States, one in five adolescents has pre-diabetes. Despite their young age,
adolescents with glucose intolerance have a high risk of complications. Thus, it is important to understand how
events that happen early in life can alter their glucose metabolism. Exposure to GDM while in-utero is an
established risk factor for offspring insulin resistance (IR). This phenomenon was first documented in the Pima
tribe by Dr. Dabelea, a co-investigator on this application: risk of diabetes was significantly higher in siblings
born after the mother developed diabetes than in those born before the mother’s diagnosis. The mechanisms
through which this happens are incompletely understood, but have important public health implications for the
transmission of diabetes across generations. We propose that one way that maternal dysglycemia might affect
offspring glucose metabolism is via alteration of offspring molecular aging pathways, particularly epigenetic
age and telomere length. Estimates of epigenetic age, generated from “epigenetic clocks,” are derived from
methylation levels at specific CpG sites, and “older” epigenetic age estimates predict mortality. In adults,
epigenetic age acceleration (EAA) predicts greater insulin resistance (IR), lower insulin secretion, and
diabetes. However, there are no studies of EAA and glucose metabolism in youth. Maternal dysglycemia also
has been reported to be linked to shorter telomere length and metabolic syndrome in offspring, but the impact
of shortening of telomere length and whether offspring experience aging across these aging mechanisms has
not been examined. Therefore, we propose to examine molecular aging and measures of glucose metabolism
in a racially diverse cohort, EPOCH, (R01DK068001) which conducted examinations and collected blood
samples at ~10 years (range 6-12 years) and ~17 years (range 12-19 years). Using existing EWAS data
(R01DK100340), we will calculate EAA in EPOCH offspring. Using existing blood samples, we will measure
telomere length using the UCSF Blackburn laboratory. We will examine whether maternal GDM is associated
with EAA and telomere shortening in offspring (Aim 1), and whether accelerated epigenetic aging and telomere
shortening are associated with glucose metabolism (Aim 2). Our preliminary data support the hypotheses that
GDM predicts offspring EAA, which in turn is associated with greater offspring IR and compensatory insulin
secretion. Our team is well-positioned to achieve the study aims, due to our familiarity with the cohorts and the
resources of the Lifecourse Epidemiology of Adiposity & Diabetes Center. We have an established track record
of collaboration. The proposed work is necessary to determine whether targeting aging biomarkers, even...

## Key facts

- **NIH application ID:** 10425757
- **Project number:** 1R21HD108508-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** CATHERINE KIM
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $247,547
- **Award type:** 1
- **Project period:** 2022-03-01 → 2024-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10425757

## Citation

> US National Institutes of Health, RePORTER application 10425757, Gestational diabetes and offspring aging and metabolism (1R21HD108508-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10425757. Licensed CC0.

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