Very Low Carbohydrate Diet as an Adjunctive Therapy for Youth Type 1 Diabetes

This prospective, open-label pilot/feasibility study of 10 youth with T1D is to evaluate glycemic and metabolic changes taking place with a very low carbohydrate diet.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Behavioral: Very Low Carbohydrate Diet

Detailed Description

First, to evaluate the feasibility of following each type of VLCD (high protein or high fat), participants will follow a standard carbohydrate diet for 2 weeks, followed by a 1 week transition to a VLCD, and then follow the a high protein VLCD for 2 weeks followed by a high fat VLCD for 2 weeks. The study will consist of 4 in person or virtual visits which will take place over ~7 weeks. All participants will be initially studied for 2 weeks while ingesting a standard diet recommended by the American Diabetes Association, followed by a 1-week transition to a VLCD, and followed by 2 weeks on each type of VLCD (high protein, high fat). During the first (baseline) period fasting β-hydroxybutyrate levels will be measured 2-3 times per week. During the VLCD study periods, fasting β-hydroxybutyrate levels will be measured daily in the morning using a blood ketone meter; insulin doses will be collected using insulin pump downloads and continuous glucose monitoring (CGM) profiles will be used to assess glycemic excursions on each diet, as well as the time in hypo-, eu- and hyperglycemic ranges. The purpose of this study is to examine changes in sensor glucose levels, basal and bolus insulin doses, and metabolic factors following implementation of a very low carbohydrate diet (VLCD). Sensor-derived time glucose ranges will serve as a surrogate marker of hemoglobin A1c given the short duration of the study. Safety measures of the diet will also be assessed, including daily fasting ketone levels.

The first hypothesis of the study is that use of a VLCD with strict monitoring of ketosis will reduce glycemic variability and increase time in target range, defined as 70-180 mg/dL by reducing the time in the hyperglycemic (>180 mg/dL) and hypoglycemic ranges (<70 mg/dL). Decreased carbohydrate intake will lead to less postprandial hyperglycemia. Lower insulin doses for meals and snacks as a result of decreased carbohydrate intake will lessen postprandial hypoglycemia as well.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale-New Haven Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• BMI 19-30 m2 for individuals at least 18 years old or BMI < 95 percentile for individuals less than 18 years old
• Participants 18 years of age must be able to read and provide written consent
• Participants under 18 years of age must be able to read and provide written assent
• Participants are managed using an insulin pump or injections
• Participant has or is willing to wear a CGM for the duration of the study
• Participant is willing to complete diet logging procedures stated above

Exclusion Criteria:

• A1c < 6.5% or > 10%
• Recent history of more than 1 of diabetic ketoacidosis (DKA) in the past 6 months
• Treatment with glucose-lowering drugs other than insulin
• Unstable psychiatric disorders, including eating disorders (DSM-V criteria)
• Weight loss medications within the last 6 months
• Females who are pregnant, lactating or planning to become pregnant in the next 6 months
• Another medical condition that precludes participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Very Low Carbohydrate Diet; Participants will follow a high protein very low carbohydrate diet (VLCD) for 2 weeks. This will be 11% of caloric intake from carbohydrates, 54% of calories from protein, and 35% of calories from fat. Immediately following this, participants will follow a high protein very low carbohydrate diet (VLCD) which will be 11% of caloric intake from carbohydrates, 23% of calories from protein, and 66% of calories from fat.

Behavioral: Very Low Carbohydrate Diet; A very low carbohydrate diet (VLCD), is defined as limiting carbohydrate intake to 11% of total daily caloric intake.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Time in Target Range of 70-180 mg/dL.	The target range is 70 mg/dL - 180 mg/dL based on sensor-derived glucose levels. The outcome is reflected as the percentage of time spent in this range during the time frame.	2 weeks per intervention, up to 7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Time Spent > 180 mg/dL to 250 mg/dl	The percent of time spent > 180 mg/dL to 250 mg/dl based on sensor-derived glucose values. Reflected is the percentage of time spent in the range of 181-250 mg/dL.	2 weeks per intervention, up to 7 weeks
Percent Time Spent > 250 mg/dL Based on Sensor-derived Glucose Values	The percent of time spent > 250 mg/dL based on sensor-derived glucose values. Presented is the percentage of time people spent in the range.	2 weeks per intervention, up to 7 weeks
Percent of Time Spent > = 55 to < 70 mg/dL Based on Sensor-derived Glucose Values	The percent of time spent > = 55 to < 70 mg/dL based on sensor-derived glucose values. Reflected is the percentage of time within range.	2 weeks per intervention, up to 7 weeks
Percent Time Spent < 55 mg/dL Based on Sensor-derived Glucose Values	The percent of time spent < 55 mg/dL based on sensor-derived glucose values during the timeframe. Presented is the percentage of overall time spent in the specified range.	2 weeks per intervention, up to 7 weeks
Total Daily Insulin Dose	The total daily insulin dose will be defined as the average total daily insulin dose will be calculated over 2 weeks. Values represent the mean units/kg/day for the 2 week period.	2 weeks per intervention, up to 7 weeks
Average Sensor Glucose Level	The average sensor glucose level recorded by the continuous glucose monitor over the 2 week dietary period in mg/dL.	2 weeks per intervention, up to 7 weeks

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): June 25, 2020
• Primary Completion (Actual): February 20, 2022
• Study Completion (Actual): February 20, 2022

Study Registration Dates

• First Submitted: September 6, 2019
• First Submitted That Met QC Criteria: September 6, 2019
• First Posted (Actual): September 9, 2019

Study Record Updates

• Last Update Posted (Actual): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: very low carbohydrate diet
• 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: 2000026189; 2K12DK094714-06 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No