Metabolic Changes Induced by a Very Low Carbohydrate Diet in Youth With Type 1 Diabetes

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

As more adolescents with type 1 diabetes (T1D) opt to follow very low carbohydrate diets to improve glucose control, it is becoming increasingly important to study the metabolic and neurological changes that occur on these diets and how these effect patient safety. Understanding the impact of dietary changes on metabolic and neurological factors will help guide clinical advice about the overall safety and efficacy of these diets in the pediatric T1D population. This work will be the basis of future studies testing dietary interventions to improve glycemic control and ensure that these dietary interventions are safe for growing youth with T1D.

Study Overview

• Status: Recruiting
• Conditions: Type1diabetes, Low Carbohydrate Diet
• Intervention / Treatment: Other: low carbohydrate diet; Other: standard carbohydrate diet

Detailed Description

The primary objective of this randomized crossover study is to determine whether a very low carbohydrate diet improves glycemic changes (measured by continuous glucose monitors) when compared to a standard carbohydrate diet in youth with type 1 diabetes.

The secondary objectives of the study are to compare metabolic changes after 2 weeks on each diet using the 2-step hyperinsulinemic euglycemic-hypoglycemic clamp and stable isotope infusions. The euglycemic portion of the clamp will allow us to determine the hepatic glucose production and adipose tissue lipolysis. Secondary objectives also include measuring the neurohormonal response to hypoglycemia after 2 weeks on each diet.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Laura M Nally, M.D.; Phone Number: 203-785-5831; Email: laura.nally@yale.edu
• Study Contact Backup: Name: Carol Alexandrescu, M.S.; Phone Number: 203-785-7022; Email: carol.alexandrescu@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Recruiting
      • Yale-New Haven Hospital
      • Contact: Laura Nally, MD; Phone Number: 203-785-5831; Email: laura.nally@yale.edu
      • Contact: Amy Steffen; Phone Number: 203-737-8852

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of type 1 diabetes for at least 1 year
• Hemoglobin A1c level < 10% within the past 2 months
• Provision of signed and dated informed consent form by the adult (if person is at least 18 years old) or parent and assent form if the participant is <18 years old.
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male, female, transgender, nonbinary are all eligible
• Diagnosis of type 1 diabetes for at least 1 year
• Insulin pump use for at least 2 months.
• Ability to perform daily blood ketone checks, wear a continuous glucose monitor, willing to wear an activity monitor, willing to adhere to the study diets and keep a diet journal.
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 4 weeks after the end of the dietary intervention.
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner

Exclusion Criteria:

• Current use of glucose-lowering agents other than insulin
• Unstable psychiatric disorders, including eating disorders
• Weight loss medications within the last 6 months
• Pregnancy or lactation, or planning pregnancy within the next 6 months
• BMI < 19 kg/m2 for individuals 18 years of age or older
• BMI < 5%ile for individuals under 18 years
• Weight less than 49 kg or 108 pounds
• Other medical conditions that may interfere with glucose metabolism and insulin sensitivity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: low carbohydrate diet; In this crossover study, participants will be randomized to either a low or standard carbohydrate for 2 weeks. Participants in the low carbohydrate group will limit carbohydrate intake to 15% of total daily calories.	Other: low carbohydrate diet; Participants will engage in a diet that limits carbohydrate intake to 15% of total daily calories for 2 weeks.
Active Comparator: standard carbohydrate diet; In this crossover study, participants will be randomized to either a low or standard carbohydrate for 2 weeks. Participants in the standard carbohydrate group will follow an ad libitum diet with standard carbohydrate intake.	Other: standard carbohydrate diet; Participants will engage in a diet that recommends standard carbohydrate intake with respect to total daily calories for 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in the optimal glucose range	Time in the optimal glucose range will be operationally defined as the percent time spent in the target range of 70-180 mg/dL during 2 weeks the diet.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time spent with hypoglycemia.	Time spent with hypoglycemia will be operationally defined as the percent time spent in the hypoglycemic (<54 mg/dL, <70 mg/dL) ranges during 2 weeks of diet.	2 weeks
Time spent with hyperglycemia	Time spent with hyperglycemia will be operationally defined as the percent time spent in the hyperglycemic (>180 mg/dL, >250 mg/dL) ranges during 2 weeks of diet.	2 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Human Factors	To describe how participants feel about and react to following a very low carbohydrate diet, interviews will be conducted. Data will be coded and emerging patterns will be combined into descriptive themes.	8 weeeks

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2021
• Primary Completion (Estimated): December 15, 2024
• Study Completion (Estimated): December 15, 2024

Study Registration Dates

• First Submitted: July 1, 2021
• First Submitted That Met QC Criteria: July 1, 2021
• First Posted (Actual): July 9, 2021

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 2000029479; 1K23DK128560-01 (U.S. NIH Grant/Contract); 2P30DK045735-26 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No