Very Low Carbohydrate Diets and Glucagon Response in T1DM

NCT ID: NCT04200391

Last Updated: 2024-12-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-03
• Study Completion Date: 2026-07-31

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 (VLC) diet. Despite these promising preliminary results, the use of VLC diets for T1D remain controversial, because of their restrictive nature and theoretical concerns regarding growth, ketoacidosis and hypoglycemia risks and efficiency of glucagon treatment for hypoglycemia. Glucagon is used as a rescue medication during severe hypoglycemia and increases blood glucose levels by mobilizing liver glycogen stores. If these stores are depleted during carbohydrate restriction, glucagon response may be inadequate and put individuals at risk for refractory hypoglycemia. A physiologic study has shown a blunted but still adequate response to glucagon in n=10 participants after following a VLCD for 1 week. Longer-term studies have not been done.

To test the hypotheses that glucagon response remains adequate while following a VLC diet in the longer term, the investigators will conduct a glucagon challenge in participants who are assigned to the VLC arm of a randomized-controlled feeding study in 32 young adults with T1D who will receive a VLC vs a standard diet for 12 weeks. After an overnight fast, twelve participants in the VLC arm will receive IV insulin to lower blood glucose levels to 60 mg/dL, followed by a glucagon injection and monitoring of blood glucose levels and other metabolic fuels.

Conditions

Type1diabetes

Keywords

nutrition; very low carbohydrate diet; ketogenic diet; nutritional ketosis; glucagon; hypoglycemia; glycogen; ketosis; ketones

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Very low carbohydrate diet

Dietary Intervention, food delivery

Group Type: EXPERIMENTAL

Very low carbohydrate diet

Intervention Type: OTHER

All meals will be delivered and participants will consume study foods exclusively. Participants will receive a fiber supplement with each meal as needed to promote digestive health, and a daily multi-vitamin, magnesium 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: 5% carbohydrate, 75% fat, 20% protein.

Interventions

Very low carbohydrate diet

All meals will be delivered and participants will consume study foods exclusively. Participants will receive a fiber supplement with each meal as needed to promote digestive health, and a daily multi-vitamin, magnesium 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: 5% carbohydrate, 75% fat, 20% protein.

Intervention Type: OTHER

Eligibility Criteria

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:

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boston Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Belinda Lennerz

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Belinda S Lennerz

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Locations

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Belinda S Lennerz, MD, PhD

Role: CONTACT

Phone: 8572183896

Email: belinda.lennerz@childrens.harvard.edu

Facility Contacts

Belinda S Lennerz

Role: primary

Other Identifiers

IRB-P00030039_3

Identifier Type: -

Identifier Source: org_study_id