# Developmental Infant Effects of Exposure to High Doses of Oral Insulin in Human Milk

> **NIH NIH K01** · UNIVERSITY OF ROCHESTER · 2022 · $56,004

## Abstract

Project Summary/Narrative (ORIGINAL APPLICATION)
 This proposal utilizes cutting-edge mechanistic approaches to investigate the clinically meaningful but hard-
to-study question of HOW insulin in human milk (HM) affects infant development. This research question is
particularly relevant to the growing and under-studied population of infants receiving HM from mothers with
obesity and/or insulin resistance (IR) - who produce milk with significantly greater insulin concentrations.
Animal models show that oral insulin delivered to the infant via breast milk has far-reaching effects on normal
offspring development and maturation. This proposal documents these effects in human infants and
investigates how effects may be altered in the context of maternal IR (and sustained infant exposure to high
concentrations of oral insulin. Specifically, we examine both systemic effects regulated by infant pancreatic
function and local intestinal effects. Importantly, we will document both acute effects during the neonatal
period AND effects of more “chronic” exposure. We will recruit 64 exclusively breastfed infants of both normal
weight/normoglycemic (NW; n=28) and mothers with IR (n=36) and study them during the neonatal period (2-4
weeks) and after more “chronic” exposure to mother's milk (5 months). Our aims are:
 Aim 1 – Cross-Sectional Study – Investigate differences in metabolic development and intestinal maturation
between infants exclusively breastfed by NW vs IR mothers at: 2-4 weeks and 5 months. We hypothesize
that infants breastfed by IR mothers will exhibit: an altered metabolomic profile indicating differences in
carbohydrate handling and insulin signaling; an altered microbial composition in the intestinal microbiome;
increased relative transcript abundance of insulin-target genes in exfoliated intestinal cells indicating more
active insulin signaling at the level of the enterocyte; and decreased intestinal permeability at 2-4 weeks.
 Aim 2 – Glycemic Study - Determine if consumption of HM from an IR mother (with high concentrations of
insulin) is correlated with differences in endogenous pancreatic response at 2-4 weeks. We hypothesize
that receipt of HM with high insulin will result in a lower endogenous pancreatic insulin response.
 Aim 3 – Glucose Tolerance Study - Determine if chronic consumption of HM from an IR mother (with high
concentrations of insulin) is correlated with pancreatic response to a glucose challenge at 5 months. We
hypothesize that chronic exposure to HM from an IR mother will under-stimulate pancreatic β-cells and result
in a dampened endogenous insulin response to a standard glucose challenge at 5 months.
Our long-term objective is to fully understand the impact of oral insulin in the development and postnatal
programming of the breastfed infant. As the prevalence of insulin resistance rises among mothers – and as
these women's offspring have increased risk of developing metabolic disease themselves – this work has far-
rea...

## Key facts

- **NIH application ID:** 10628678
- **Project number:** 3K01DK115710-05S1
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Bridget E Young
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $56,004
- **Award type:** 3
- **Project period:** 2018-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10628678

## Citation

> US National Institutes of Health, RePORTER application 10628678, Developmental Infant Effects of Exposure to High Doses of Oral Insulin in Human Milk (3K01DK115710-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10628678. Licensed CC0.

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