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

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.

Study Overview

• Status: Recruiting
• Conditions: Type1diabetes
• Intervention / Treatment: Other: very low carbohydrate diet; Other: standard carbohydrate diet

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Belinda Lennerz, MD PhD; Phone Number: 8572183896; Email: belinda.lennerz@childrens.harvard.edu
• Study Contact Backup: Name: Svetlana Azova, MD; Phone Number: 6179196675; Email: svetlana.azova@childrens.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Contact: Svetlana Azova, MD; Phone Number: 6179196675; Email: svetlana.azova@childrens.harvard.edu
      • Contact: Belinda S Lennerz, MD PhD; Phone Number: 857-218-3896; Email: belinda.lennerz@childrens.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 exclusion criteria
  2. Irregular menses
  3. 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: very low carbohydrate diet; Dietary Intervention, food delivery	Other: very low carbohydrate diet; 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.
Active Comparator: standard diet; Dietary Intervention, food delivery	Other: standard carbohydrate diet; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Boston Children's Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2020
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: October 16, 2018
• First Submitted That Met QC Criteria: October 17, 2018
• First Posted (Actual): October 18, 2018

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 29, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: nutrition; ketogenic diet; metabolism; very low carbohydrate diet; nutritional ketosis; ketosis; metabolic health
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: IRB-P00030039

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No