Type1diabetes, Low Carbohydrate Diet
Conditions
Brief summary
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
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.
Interventions
OTHERlow carbohydrate diet
Participants will engage in a diet that limits carbohydrate intake to 15% of total daily calories for 2 weeks.
Participants will engage in a diet that recommends standard carbohydrate intake with respect to total daily calories for 2 weeks.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 21 Years
Healthy volunteers
No
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 * All sexes are 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Time in the Optimal Glucose Range | 2 weeks | 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 the 2 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Time Spent With Hypoglycemia. | 2 weeks | Time spent with hypoglycemia will be operationally defined as the percent time spent in the hypoglycemic ranges during 2 weeks of diet. Level 2 hypoglycemia defined as \<54 mg/dL. Level 1 hypoglycemia defined as 54-69 mg/dL. |
| Percent Time Spent With Hyperglycemia | 2 weeks | Time spent with hyperglycemia will be operationally defined as the percent time spent in the hyperglycemic ranges during 2 weeks of diet. Level 1 hyperglycemia defined as 181-250 mg/dL. Level 2 hyperglycemia defined as \>250 mg/dL. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Human Factors | 8 weeeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Carbohydrate Diet, Then Standard 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.
low carbohydrate diet: Participants will engage in a diet that limits carbohydrate intake to 15% of total daily calories for 2 weeks. | 9 |
| Standard Carbohydrate Diet, Then Low 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.
standard carbohydrate diet: Participants will engage in a diet that recommends standard carbohydrate intake with respect to total daily calories for 2 weeks. | 10 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 2 | Discontinued intervention | 1 | 2 |
Baseline characteristics
| Characteristic | Low Carbohydrate Diet, Then Standard Carbohydrate Diet | Total | Standard Carbohydrate Diet, Then Low Carbohydrate Diet |
|---|---|---|---|
| Age, Continuous | 17 years STANDARD_DEVIATION 3 | 17 years STANDARD_DEVIATION 2.57 | 17 years STANDARD_DEVIATION 2.67 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 6 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 13 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 15 Participants | 7 Participants |
| Region of Enrollment United States | 9 participants | 19 participants | 10 participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 3 Participants |
| Sex: Female, Male Male | 5 Participants | 12 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 19 | 0 / 19 |
| other Total, other adverse events | 8 / 19 | 8 / 19 | 1 / 19 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 | 0 / 19 |
Outcome results
Primary
Percent 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 the 2 weeks.
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low Carbohydrate Diet | Percent Time in the Optimal Glucose Range | 71.20 percentage of time |
| Standard Carbohydrate Diet | Percent Time in the Optimal Glucose Range | 62.51 percentage of time |
p-value: <0.001t-test, 1 sided
Secondary
Percent Time Spent With Hyperglycemia
Time spent with hyperglycemia will be operationally defined as the percent time spent in the hyperglycemic ranges during 2 weeks of diet. Level 1 hyperglycemia defined as 181-250 mg/dL. Level 2 hyperglycemia defined as \>250 mg/dL.
Time frame: 2 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Low Carbohydrate Diet | Percent Time Spent With Hyperglycemia | 181-250 mg/dL | 19.93 percentage of time |
| Low Carbohydrate Diet | Percent Time Spent With Hyperglycemia | >250 mg/dL | 7.19 percentage of time |
| Standard Carbohydrate Diet | Percent Time Spent With Hyperglycemia | 181-250 mg/dL | 23.20 percentage of time |
| Standard Carbohydrate Diet | Percent Time Spent With Hyperglycemia | >250 mg/dL | 12.5 percentage of time |
Comparison: 181-250 mg/dLp-value: 0.006t-test, 1 sided
Comparison: \>250 mg/dLp-value: <0.001t-test, 1 sided
Secondary
Percent Time Spent With Hypoglycemia.
Time spent with hypoglycemia will be operationally defined as the percent time spent in the hypoglycemic ranges during 2 weeks of diet. Level 2 hypoglycemia defined as \<54 mg/dL. Level 1 hypoglycemia defined as 54-69 mg/dL.
Time frame: 2 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Low Carbohydrate Diet | Percent Time Spent With Hypoglycemia. | <54 mg/dL | 0.42 percentage of time |
| Low Carbohydrate Diet | Percent Time Spent With Hypoglycemia. | 54-69 mg/dL | 1.27 percentage of time |
| Standard Carbohydrate Diet | Percent Time Spent With Hypoglycemia. | <54 mg/dL | 0.33 percentage of time |
| Standard Carbohydrate Diet | Percent Time Spent With Hypoglycemia. | 54-69 mg/dL | 1.46 percentage of time |
Comparison: \<54 mg/dLp-value: 0.57t-test, 1 sided
Comparison: 54-69 mg/dLp-value: 0.43t-test, 1 sided
Other Pre-specified
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.
Time frame: 8 weeeks