# Serotonin as a Novel Biomarker for Progression to Type 2 Diabetes in Obese Adolescents

> **NIH NIH K23** · DUKE UNIVERSITY · 2021 · $187,891

## Abstract

PROJECT SUMMARY:
Type 2 diabetes (T2D) is a worldwide pandemic affecting nearly 300 million adults and a rapidly increasing
number of children, with profound individual and community health consequences. Estimated diabetes costs in
the United States now exceed $200 billion. It is the major cause of blindness, leg amputation, and end-stage
kidney disease and a principal cause of myocardial infarction and stroke. The two major determinants of T2D
are obesity and insulin resistance (IR), yet the pathogenesis of T2D remains poorly understood. Only one-half
of obese children are IR, and a far lower percentage progress to T2D. Why some obese children avoid metabolic
dysfunction while others develop T2D is a critical gap in in the understanding of T2D pathogenesis and precludes
the design and implementation of programs for diabetes prevention and treatment. My long-term career goal is
to establish an independent research program dedicated to identifying and treating obese children at highest risk
for IR and T2D. Using state-of-the-art metabolomic profiling of plasma samples, we previously found that
childhood IR is associated with increased levels of the branch-chain amino acids (BCAA). Recently we have
employed metabolic profiling of 24-hour urine samples, which has the advantage of integrating differences in
metabolic status over time non-invasively. We identified a decrease in urine 5-Hydroxyindoleacetic acid (5-
HIAA), the major metabolite of serotonin, as a novel biomarker associated with T2D in obese youth. This finding
is particularly interesting given that serotonin increases pancreatic β-cell replication, β-cell mass, and glucose-
stimulated insulin secretion. The reduction in 5HIAA in T2D likely reflects a decrease in cellular serotonin
availability, since: (a) elevated BCAA compete with tryptophan, the precursor of serotonin, for uptake into β-cells
and other tissues; and (b) in obesity, tryptophan metabolism is dysregulated and shifted towards production of
kynurenine rather than serotonin. These findings suggest that reductions in tryptophan availability and serotonin
production contribute to diabetes pathogenesis through inhibition of insulin secretion, promoting progression
from obesity to glucose intolerance and T2D. We hypothesize that serotonin and serotonin metabolites
including 5-HIAA constitute useful urine biomarkers that predict development of T2D in obese youth. This
hypothesis will be tested in three Specific Aims. Aim 1 will identify urinary metabolic signatures that differ
among non-obese and obese children with and without T2D. Aim 2 will determine if these urinary metabolic
signatures correlate with parameters of glucose tolerance and glycemic control. Aim 3 will determine if urinary
5-HIAA measured at baseline or during follow-up predicts changes in disposition index, a composite measure of
β-cell function in a longitudinal study of lean and obese subjects without T2D. My mentoring team, which includes
Drs. Christopher Newg...

## Key facts

- **NIH application ID:** 10249226
- **Project number:** 5K23DK117067-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Pinar Gumus Balikcioglu
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $187,891
- **Award type:** 5
- **Project period:** 2018-09-07 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249226

## Citation

> US National Institutes of Health, RePORTER application 10249226, Serotonin as a Novel Biomarker for Progression to Type 2 Diabetes in Obese Adolescents (5K23DK117067-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10249226. Licensed CC0.

---

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