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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Type1diabetes, Low Carbohydrate Diet

Intervention / Treatment
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* Other: low carbohydrate diet
* Other: standard carbohydrate diet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: low carbohydrate diet<br>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<br>* Participants will engage in a diet that limits carbohydrate intake to 15% of total daily calories for 2 weeks.<br>|
| Active Comparator: standard carbohydrate diet<br>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<br>* Participants will engage in a diet that recommends standard carbohydrate intake with respect to total daily calories for 2 weeks.<br>|

What is the study measuring?
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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 |