# Examining a mechanism for insulin resistance in short sleeping adolescents: Melatonin, food intake, and the role of a melatonin receptor gene variant (MTNR1B)

> **NIH NIH R03** · UNIVERSITY OF COLORADO DENVER · 2023 · $116,625

## Abstract

PROJECT SUMMARY
Physiological and psychosocial factors that result in insufficient sleep and circadian misalignment may confer a
unique risk towards obesity and dysmetabolism in youth. Our pilot data demonstrates that insufficient sleep
and circadian misalignment in adolescents with obesity are associated with metabolic dysregulation as
assessed via oral glucose tolerance test. One possible mechanism for the relationship between insufficient
sleep, circadian misalignment, and reduced insulin sensitivity (Si) is the timing of dietary intake and circulating
melatonin levels. Dietary intake during times of high melatonin may lead to glucose dysregulation and
increased risk of type 2 diabetes (T2D). Adolescents, often awake in the hours of wake after/before melatonin
onset/offset when melatonin levels are high and food intake may occur, may be particularly at risk. A common
melatonin receptor gene variant is a risk factor for reduced Si and T2D in adults, and may have greater effect
in younger individuals, but the functional impact of the variant in adolescents has not been studied. Intervening
to increase sleep duration may improve Si in habitually short sleeping adolescents in part by aligning their
circadian clock to the timing of sleep and eating occasions, and initial data from my K23 demonstrates this is
feasible. Our central hypothesis is that the dysmetabolism and adverse dietary timing induced by insufficient
sleep and circadian misalignment can be mitigated by improving sleep and circadian health. Further, we
hypothesize that presence of the risk allele (G) will confer additional risk in habitually short sleeping
adolescents. We propose to leverage our ongoing K23 study by adding additional participants, photographic
diet diaries, continuous glucose monitoring, and genotyping to examine the effect of concurrent food intake and
elevated endogenous melatonin on Si and glycemic variability after one week of typical insufficient sleep,
change in timing of food intake relative to melatonin following a one-week sleep extension manipulation, and
differential risk due to genotype. The proposed project will provide additional training in genetics, build new
collaborations, and provide pilot data for an important new area of study that will help move the PI towards
research independence in applying for an R01. This study will launch our efforts to determine countermeasures
such as behavioral sleep or dietary interventions, timed bright light exposure, and pharmacological treatments
such as melatonin agonists to mitigate the effect of insufficient sleep and circadian misalignment on IR for high
risk adolescents, including those obtaining insufficient sleep, late and early eaters, exogenous melatonin users,
and MTNR1B G allele carriers.

## Key facts

- **NIH application ID:** 10701803
- **Project number:** 5R03DK131225-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Stacey Lynn Simon
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $116,625
- **Award type:** 5
- **Project period:** 2022-09-10 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10701803

## Citation

> US National Institutes of Health, RePORTER application 10701803, Examining a mechanism for insulin resistance in short sleeping adolescents: Melatonin, food intake, and the role of a melatonin receptor gene variant (MTNR1B) (5R03DK131225-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10701803. Licensed CC0.

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