Type 1 Diabetes Management Using a Very Low Carbohydrate Versus Standard Diet

Study Overview
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Brief Summary
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Despite major technological advances, management of type one diabetes mellitus (T1D) remains suboptimal, putting millions of people at risk for immediate and long-term complications. After meals, a mismatch between carbohydrate absorption rate and insulin action typically leads to alternating periods of hyper- and hypoglycemia. A conceptually promising approach to control both problems is dietary carbohydrate restriction to reduce postprandial blood glucose changes and insulin needs. In a prior survey study, the investigators documented exceptional glycemic control (HbA1c 5.67%) and low acute complication rates among 316 children and adults with T1D consuming a very-low-carbohydrate diet. To test the feasibility of this approach, the investigators will conduct a randomized-controlled feeding study involving 32 adults and adolescents with T1D. Participants will be randomized to receive a very low carbohydrate vs. standard carbohydrate diet. Participants will be in the study for 12 weeks and receive all their meals by meal delivery.They will share continuous glucose monitoring data with the study team and be in close communication to adjust insulin doses as needed. All participants will have a screening visit, an individual or group education session, and 3 study visits to evaluate diabetes control and metabolic health. Some of these visits will have a fasting blood draw. Two of the visits will also comprise additional metabolic studies to assess glucagon response and brain function during hypoglycemia by magnetic resonance imaging (MRI). Participants will have IV catheters placed and receive IV insulin to drop blood glucose levels to 50 mg/dl for up to 30 minutes. The primary outcome will be HbA1c change from baseline. Secondary outcomes include detailed measures of glycemic variability, metabolic health, and quality of life.

Official Title
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Type 1 Diabetes Management Using a Very Low Carbohydrate Versus Standard Diet

Conditions
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Type1diabetes

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females with T1D for at least 1 year Age 18 to 40 years Tanner stage ≥ IV BMI 18.5-35 kg/m2 Stable glycemic control (HbA1c 6.5-9%) Use of a continuous glucose monitor (CGM) Use of an insulin pump Attendance of at least 1 diabetes care visit over the past 12 months (including virtual) Exclusion Criteria: Ketoacidosis or severe hypoglycemia with seizure or coma in the past 6 months Dietary restrictions or intolerances that are incompatible with the planned food deliveries, e.g. celiac disease, gastroparesis, certain food allergies Following a weight-loss or otherwise restrictive diet Vigorous exercise >2 hours on >3 days a week History of an eating disorder or at risk for eating disorder, assessed by the Eating Disorders Diagnostic Scale (EDDS) Major medical illness or use of medications other than insulin and metformin that could interfere with metabolic or glycemic variables Significant psychiatric illness Smoking, use of recreational drugs, or excessive alcohol consumption Pregnancy or breastfeeding Anemia For participants who undergo MRI: Standard MRI exclusion criteria Irregular menses Use of psychotropic medication other than SSRIs or other mild antidepressant or anxiety medications (unless these medications are safe to be held for several days to allow for the acquisition of MRI data)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized controlled trial, 12-week feeding study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: very low carbohydrate diet<br>Dietary Intervention, food delivery | Other: very low carbohydrate diet<br>* All meals will be delivered and participants will consume study foods exclusively. Participants will receive a fiber supplement as needed with each meal to support digestive health, and a daily multi-vitamin, magnesium and omega-three supplement to ascertain micronutrient sufficiency. Participants will be weighed at each study visit and the diet plan will be adjusted for satiety and weight-maintenance. The diet composition will be as follows: 5% carbohydrate, 70% fat, 20% protein.<br>|
| Active Comparator: standard diet<br>Dietary Intervention, food delivery | Other: standard carbohydrate diet<br>* All meals will be delivered and participants will consume study foods exclusively. Participants will receive a daily multi-vitamin and omega-3 supplement to ascertain micronutrient sufficiency. Participants will be weighed at each study visit and the diet plan will be adjusted for satiety and weight-maintenance. The diet composition will be as follows: 50% carbohydrate, 30% fat, 20% protein.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin A1C change | HbA1C change from baseline at 12 weeks will be compared between the 2 interventions | 12 weeks - baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| total daily insulin dose | average daily insulin dose over 1 week will be calculated | week 0 and 12 | 
| percent time spent in the glycemic target range of 70-140 mg/dl | will be calculated from 1-week continuous glucose monitoring data | week 0 and 12 | 
| percent time spent below the glycemic target of 70 mg/dl | will be calculated from 1-week continuous glucose monitoring data | week 0 and 12 | 
| percent time in hypoglycemia below 54 mg/dl | will be calculated from 1-week continuous glucose monitoring data | week 0 and 12 | 
| percent time spent above the glycemic target of 140 mg/dl | will be calculated from 1-week continuous glucose monitoring data | week 0 and 12 | 
| percent time spent in hyperglycemia | will be calculated from 1-week continuous glucose monitoring data | week 0 and 12 | 
| blood glucose average | will be calculated from 1-week continuous glucose monitoring data | week 0 and 12 | 
| blood glucose standard deviation | will be calculated from 1-week continuous glucose monitoring data | week 0 and 12 | 
| Glycemic Variability Index, a measure for glycemic variability normalized to mean blood glucose level | will be calculated by dividing blood glucose standard deviation by blood glucose average | week 0 and 12 | 
| Mean Amplitude of Glycemic Excursions (MAGE), a measure for postprandial glycemic variability | will be calculated by dividing blood glucose standard deviation by blood glucose average | week 0 and 12 | 
| fasting total cholesterol | from venous blood | week 0 and 12 | 
| fasting high density lipoprotein cholesterol | from venous blood | week 0 and 12 | 
| fasting low density lipoprotein cholesterol | from venous blood | week 0 and 12 | 
| fasting triglycerides | from venous blood | week 0 and 12 | 
| fasting beta hydroxybutyrate | from venous blood and/or point-of-care testing | weeks 0, 1, 2, 4, 6, 9, 12 | 
| fasting high-sensitivity c-reactive protein | from venous blood | week 0 and 12 | 
| Self-reported quality of life assessed per self-report by The Problem Areas in Diabetes Scale (PAID) | The scores for each item are summed, then multiplied by 1.25 to generate a total score out of 100. | week 0, 6, and 12 | 
| Becks Depression Inventory II (BDI II) less suicidality | BDI-II less suicidality is a 20-item self-report inventory that measures assesses for presence and severity of depression depressive symptoms. Each item is scored between 0-3. Item scores are added up to a total score (max. 60) and reported. | week 0, 6, and 12 | 
| Yale Food Addiction Scale 2.0 (YFAS 2.0) | Assesses indicators of addictive-like eating.The YFAS includes two scoring options: 1) a symptom count that reflects the number of addiction-like criteria endorsed and 2) a dichotomous diagnosis that indicates whether a threshold of three or more symptoms plus clinically significant impairment or distress has been met. The diagnosis score will be calculated at baseline and used as an effect modifier. Symptom counts will be reported separately as a longitudinal measure. | week 0, 6, and 12 | 
| Highly Processed Food Withdrawal Scale (ProWS) | Assesses withdrawal-type symptoms that may occur when individuals cut down on rewarding foods. | Baseline, daily on days 1-7, then weekly; primary focus on change from baseline to day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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very low carbohydrate diet, nutrition, ketogenic diet, ketosis, nutritional ketosis, metabolism, metabolic health