Very Low Carbohydrate Diets and Glucagon Response in T1DM

Type1diabetes Clinical Trial

Official title:

Glucagon Response in Patients With Type 1 Diabetes Mellitus Following a Very Low Carbohydrate

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04200391
• Other study ID #: IRB-P00030039_3
• Status: Recruiting
• Phase: N/A
• Start date: January 3, 2020
• Est. completion date: July 31, 2024

Study information

• Verified date: June 2023
• Source: Boston Children's Hospital
• Contact: Belinda S Lennerz, MD, PhD
• Phone: 8572183896
• Email: belinda.lennerz[@]childrens.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: July 31, 2024
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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).

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Type1diabetes

Intervention

Other:
• 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.

Locations

Country	Name	City	State
United States	Boston Children's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Boston Children's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Recovery from symptoms of hypoglycemia	Recovery from hypoglycemia symptoms will be assessed using a Hypoglycemia Symptoms Scale at baseline, when blood glucose is < 75 mg/dL, pre-dose, and at 15, 30, 45, 60, 75, and 90 minutes following administration of glucagon. The Hypoglycemia Symptoms Scale measures the intensity of 14 commonly experienced hypoglycemic symptoms on a scale from 0 (not present) to 6 (very intense). The higher the score, the more intense the hypoglycemia symptoms. The sum of each symptom score would yield a range of 0 to 84 (e.g., 14 x 6 = 84). The total score will be calculated as the sum of each symptom score and summarized at each time point.	week 5-12 on the very low carbohydrate diet
Secondary	Time to achieve glucagon treatment success	The mean time from glucagon administration to blood glucose = 70 mg/dL or an increase = 20 mg/dL in blood glucose from nadir. 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	Plasma levels of beta-hydroxybutyrate following glucagon administration	Levels will be measured at baseline, pre-dose, and at 10, 20, 30, 45, 60, and 90 minutes. Average levels at each time point, peak level, and area under the curve (AUC) will be reported.	week 5-12 on the very low carbohydrate diet
Secondary	Plasma levels of free fatty acids following glucagon administration	Levels will be measured at baseline, pre-dose, 10, 20, 30, 45, 60, and 90 minutes. Average levels at each time point, peak level, and area under the curve (AUC) will be reported.	week 5-12 on the very low carbohydrate diet
Secondary	Plasma glucose levels following glucagon administration	Levels will be measured at baseline, pre-dose, and at 10, 20, 30, 45, 60, and 90 minutes. Average levels at each time point, peak level, and area under the curve (AUC) will be reported.	week 5-12 on the very low carbohydrate diet