# Metabolic and Neurological Changes Induced by a Very Low Carbohydrate Diet in Youth with Type 1 Diabetes

> **NIH NIH K23** · YALE UNIVERSITY · 2022 · $193,016

## Abstract

PROJECT SUMMARY/ABSTRACT
 Thirty years of follow up data from two landmark trials (DCCT/EDIC) demonstrates that intensive insulin
management to achieve near-normal blood glucose levels decreases the risk of retinopathy, neuropathy, and
nephropathy for individuals with type 1 diabetes (T1D).1,2 Yet, achieving near-normal blood glucose levels
increases the risk of severe hypoglycemia in those with T1D by 3-fold. Currently, there are no specific dietary
recommendations from the American Diabetes Association for pediatric T1D;3 however, a growing number of
youth with T1D and their parents are interested in very low carbohydrate diets to improve blood glucose
control.4
There has been hesitance to prescribe such diets to adolescents as no rigorous studies have been
performed in this age group.
The goal of this proposal is to determine the safety and efficacy of a very low
carbohydrate diet in adolescents with T1D by looking at metabolic and neurological changes that occur with
this diet. Aim 1 of this proposal uses a randomized crossover study design to compare the time spent in the
target range using continuous glucose monitors when adolescents with T1D follow a standard versus very low
carbohydrate diet. Less time in the hyperglycemic and hypoglycemic ranges indicates better safety. The
number of episodes of diabetic ketoacidosis and severe hypoglycemia will also be reported. Aim 2 will
compare the counterregulatory hormone response to hypoglycemia between the 2 diets using the 2-step
hyperinsulinemic euglycemic-hypoglycemic clamp technique.
Stable isotope infusions will be used to assess
rates of hepatic glucose production (glucose release from the liver) and
glycerol metabolism from adipose
tissue. Further, very low carbohydrate diets are likely to cause higher ketone levels in the blood (nutritional
ketosis), but there is little known about how this will affect awareness of hypoglycemia and other neurological
changes. Aim 3 will assess changes in symptoms of hypoglycemia using validated questionnaires during the
hypoglycemia portion of the
clamp, which will be correlated with fMRI findings.
Through this aim, we will
determine if the ketosis that develops in very low carbohydrate diets will blunt warning signs of hypoglycemia.
Dr. Nally has assembled a leadership team with a diverse skillset to guide her in this research. Dr. Nally's
primary mentor, Dr. William Tamborlane, has over 45 years of experience in pediatric T1D research and has
mentored 14 current physician scientist faculty at Yale. Dr. Raimund Herzog (co-mentor) has expertise in the
metabolic effects of hypoglycemia and ketosis on the brain and will guide Dr. Nally with these aspects of the
study. With expertise in pediatric T1D, continuous glucose monitoring and the hyperinsulinemic euglycemic-
hypoglycemic clamps, Dr. Jennifer Sherr (co-mentor) will ensure Dr. Nally has the skillset necessary to conduct
the studies proposed herein. Dr. Nally will gain expertise in sophisticated measur...

## Key facts

- **NIH application ID:** 10455443
- **Project number:** 5K23DK128560-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Laura Marie Nally
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $193,016
- **Award type:** 5
- **Project period:** 2021-08-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455443

## Citation

> US National Institutes of Health, RePORTER application 10455443, Metabolic and Neurological Changes Induced by a Very Low Carbohydrate Diet in Youth with Type 1 Diabetes (5K23DK128560-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10455443. Licensed CC0.

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