Clinical trial NCT04200391: Very Low Carbohydrate Diets and Glucagon Response in T1DM
Official title: Glucagon Response in Patients With Type 1 Diabetes Mellitus Following a Very Low Carbohydrate
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type1diabetes
Keywords: nutrition
very low carbohydrate diet
ketogenic diet
nutritional ketosis
glucagon
hypoglycemia
glycogen
ketosis
ketones
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
First posted: 2019-12-16
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Participants will receive a very low carbohydrate diet for 12 weeks and undergo a glucagon challenge during weeks 5-12 to assess glycemic response.
Primary purpose: SUPPORTIVE_CARE

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.


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:

  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).

Primary outcomes:
measure: 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
timeFrame: week 5-12 on the very low carbohydrate diet
Secondary outcomes:
measure: Recovery from symptoms of hypoglycemia
timeFrame: week 5-12 on the very low carbohydrate diet
measure: Time to achieve glucagon treatment success
timeFrame: week 5-12 on the very low carbohydrate diet
measure: Plasma levels of beta-hydroxybutyrate following glucagon administration
timeFrame: week 5-12 on the very low carbohydrate diet
measure: Plasma levels of free fatty acids following glucagon administration
timeFrame: week 5-12 on the very low carbohydrate diet
measure: Plasma glucose levels following glucagon administration
timeFrame: week 5-12 on the very low carbohydrate diet
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: Belinda S Lennerz
role: PRINCIPAL_INVESTIGATOR
References: