# Epigenetic Markers of Short- and Long- Term Near-Normoglycemia Remission in Patients with Ketosis-Prone Diabetes

> **NIH NIH K23** · EMORY UNIVERSITY · 2021 · $190,080

## Abstract

Project Summary/Abstract
Ketosis-prone diabetes mellitus (KPDM) affects ~20-50% of African American patients with newly diagnosed
diabetes who present with diabetic ketoacidosis (DKA). At presentation of DKA, these patients have a severe
decompensation in insulin secretion (beta-cell function) accompanied by severe insulin resistance. Unlike
patients with type 1 diabetes, following intensive insulin treatment, many of these patients exhibit
improvements in insulin secretion and insulin sensitivity and are able to discontinue insulin therapy (near-
normoglycemia remission, HbA1c < 7%). The period of near-normoglycemia remission is variable and many
patients eventually experience a hyperglycemic relapse or even DKA. Therefore, studying the underlying
mechanisms leading to changes in insulin secretion and sensitivity and near-normoglycemia remission has
implications for a significant number of African American patients with diabetes.
DNA methylation and gene expression, have been proposed as mechanisms that affect insulin secretion and
insulin sensitivity. In this proposal, based on preliminary results, the PI Priyathama Vellanki, MD, will test
whether longitudinal gene expression and DNA methylation changes in specific pathways affect quantitative
traits of insulin sensitivity and secretion along with achievement and maintenance of near-normoglycemia
remission. In Aim1, she will characterize whether gene expression and DNA methylation changes in glucose
sensing and insulin secretion pathways associate with quantitative measures of insulin secretion derived from
glucagon stimulation tests. In Aim 2, she will characterize glucose uptake and insulin signaling pathways with
quantitative traits of insulin sensitivity from frequently-sampled IV glucose tolerance tests (FSIVGTT). She will
also test whether gene expression and methylation in these pathways associate with short- and long-term
near-normoglycemia remission. Further, in order to develop blood-based biomarkers, she will test whether
gene expression and DNA methylation in muscle correlate with those in blood. Successful completion of these
aims will yield important insights into mechanisms that underlie changes in insulin sensitivity and secretion
through the clinical course of patients with KPDM.
The proposed aims will be performed under the guidance of an expert interdisciplinary mentorship team led by
her lead mentor Dr. Umpierrez (expertise in KPDM) and co-mentor Dr. Alicia K. Smith (expert in epigenetics)
along with an advisory committee comprised of experts in statistical genetics (Dr. Karen Conneely) and
computational biology (Dr. Darko Stefanovski). Emory University is a world-class institution that has adequate
and ample resources necessary to carry out the research aims, including the Georgia Clinical and Translation
Science Alliance. Her structured training plan has formal didactic training at Emory along with hand-on training
in performance of phenotyping studies and data analyses. T...

## Key facts

- **NIH application ID:** 10197897
- **Project number:** 5K23DK113241-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Priyathama Vellanki
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $190,080
- **Award type:** 5
- **Project period:** 2019-07-16 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197897

## Citation

> US National Institutes of Health, RePORTER application 10197897, Epigenetic Markers of Short- and Long- Term Near-Normoglycemia Remission in Patients with Ketosis-Prone Diabetes (5K23DK113241-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10197897. Licensed CC0.

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