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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| very low carbohydrate diet | Experimental | Dietary Intervention, food delivery |
|
| standard diet | Active Comparator | Dietary Intervention, food delivery |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| very low carbohydrate diet | Other | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Hemoglobin A1C change | HbA1C change from baseline at 12 weeks will be compared between the 2 interventions | 12 weeks - baseline |
| 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 |
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Inclusion Criteria:
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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Belinda Lennerz, MD PhD | Contact | 8572183896 | belinda.lennerz@childrens.harvard.edu | |
| Azova | Contact |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Boston Children's Hospital | Recruiting | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29735574 | Background | Lennerz BS, Barton A, Bernstein RK, Dikeman RD, Diulus C, Hallberg S, Rhodes ET, Ebbeling CB, Westman EC, Yancy WS Jr, Ludwig DS. Management of Type 1 Diabetes With a Very Low-Carbohydrate Diet. Pediatrics. 2018 Jun;141(6):e20173349. doi: 10.1542/peds.2017-3349. Epub 2018 May 7. |
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| ID | Term |
|---|---|
| D007662 | Ketosis |
| ID | Term |
|---|---|
| D000138 | Acidosis |
| D000137 | Acid-Base Imbalance |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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randomized controlled trial, 12-week feeding study
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| standard carbohydrate diet | Other | 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. |
|
| 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 |