Type1diabetes
Conditions
Keywords
very low carbohydrate diet, nutrition, ketogenic diet, ketosis, nutritional ketosis, metabolism, metabolic health
Brief summary
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.
Interventions
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.
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.
Sponsors
Boston Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
randomized controlled trial, 12-week feeding study
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
No
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: 1. Standard MRI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin A1C change | 12 weeks - baseline | HbA1C change from baseline at 12 weeks will be compared between the 2 interventions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| total daily insulin dose | week 0 and 12 | average daily insulin dose over 1 week will be calculated |
| percent time spent in the glycemic target range of 70-140 mg/dl | week 0 and 12 | will be calculated from 1-week continuous glucose monitoring data |
| percent time spent below the glycemic target of 70 mg/dl | week 0 and 12 | will be calculated from 1-week continuous glucose monitoring data |
| percent time in hypoglycemia below 54 mg/dl | week 0 and 12 | will be calculated from 1-week continuous glucose monitoring data |
| percent time spent above the glycemic target of 140 mg/dl | week 0 and 12 | will be calculated from 1-week continuous glucose monitoring data |
| percent time spent in hyperglycemia | week 0 and 12 | will be calculated from 1-week continuous glucose monitoring data |
| blood glucose average | week 0 and 12 | will be calculated from 1-week continuous glucose monitoring data |
| Glycemic Variability Index, a measure for glycemic variability normalized to mean blood glucose level | week 0 and 12 | will be calculated by dividing blood glucose standard deviation by blood glucose average |
| Mean Amplitude of Glycemic Excursions (MAGE), a measure for postprandial glycemic variability | week 0 and 12 | will be calculated by dividing blood glucose standard deviation by blood glucose average |
| blood glucose standard deviation | week 0 and 12 | will be calculated from 1-week continuous glucose monitoring data |
| fasting high density lipoprotein cholesterol | week 0 and 12 | from venous blood |
| fasting low density lipoprotein cholesterol | week 0 and 12 | from venous blood |
| fasting triglycerides | week 0 and 12 | from venous blood |
| fasting beta hydroxybutyrate | weeks 0, 1, 2, 4, 6, 9, 12 | from venous blood and/or point-of-care testing |
| fasting high-sensitivity c-reactive protein | week 0 and 12 | from venous blood |
| Self-reported quality of life assessed per self-report by The Problem Areas in Diabetes Scale (PAID) | week 0, 6, and 12 | The scores for each item are summed, then multiplied by 1.25 to generate a total score out of 100. |
| Becks Depression Inventory II (BDI II) less suicidality | week 0, 6, and 12 | 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. |
| Yale Food Addiction Scale 2.0 (YFAS 2.0) | week 0, 6, and 12 | 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. |
| Highly Processed Food Withdrawal Scale (ProWS) | Baseline, daily on days 1-7, then weekly; primary focus on change from baseline to day 7 | Assesses withdrawal-type symptoms that may occur when individuals cut down on rewarding foods. |
| fasting total cholesterol | week 0 and 12 | from venous blood |
Countries
United States
Contacts
Primary ContactBelinda Lennerz, MD PhD
Backup ContactAzova
Outcome results
None listed