Very Low Carbohydrate Diets and Glucagon Response in T1DM

NCT04200391 | Recruiting DMC

• 1 other identifier: IRB-P00030039_3
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Glucagon treatment success, defined as an increase in glucose level to ≥ 70 mg/dL or an Increase of ≥ 20 mg/dL from glucose nadir within 30 minutes after receiving 1 mg glucagon IM

  Point-of-care blood glucose levels will be measured pre-dose and every 5 minutes for 30 minutes and until BG is ≥ 70 mg/dL (whichever occurs later), then gradually spaced per MD orders to align with the rest of the labs

  week 5-12 on the very low carbohydrate diet

Secondary Outcomes (5)

• Recovery from symptoms of hypoglycemia

  week 5-12 on the very low carbohydrate diet

• Time to achieve glucagon treatment success

  week 5-12 on the very low carbohydrate diet

• Plasma levels of beta-hydroxybutyrate following glucagon administration

  week 5-12 on the very low carbohydrate diet

• Plasma levels of free fatty acids following glucagon administration

  week 5-12 on the very low carbohydrate diet

• Plasma glucose levels following glucagon administration

  week 5-12 on the very low carbohydrate diet

Study Arms (1)

Very low carbohydrate diet

EXPERIMENTAL

Dietary Intervention, food delivery

Other: Very low carbohydrate diet

Interventions

Very low carbohydrate diet 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.

Very low carbohydrate diet

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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:
• 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).

Sponsors & Collaborators

• Boston Children's Hospital: lead

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

MeSH Terms

Conditions

Hypoglycemia; Ketosis

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Acidosis; Acid-Base Imbalance

Study Officials

• Belinda S Lennerz

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Belinda S Lennerz, MD, PhD

CONTACT

8572183896; belinda.lennerz@childrens.harvard.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Participants will receive a very low carbohydrate diet for 12 weeks and undergo a glucagon challenge during weeks 5-12 to assess glycemic response.

Study Record Dates

• First Submitted: December 12, 2019
• First Posted: December 16, 2019
• Study Start: January 3, 2020
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: December 18, 2024

Record last verified: 2024-12

Locations

US (1)