Glucagon Efficiency After High and Low Carbohydrate Diet

Study Overview
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Brief Summary
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No studies have investigated if the dietary composition of carbohydrate influences the glycaemic effect of single and multiple boluses of subcutaneous low-dose glucagon. Further, the recommended diet composition to patients with type 1 diabetes has not been thoroughly validated. Many patients with type 1 diabetes practice low carbohydrate eating patterns due to the assumption that this diet can reduce fluctuations in plasma glucose. Before glucagon can be used as an add-on to intensive insulin treatment, these aspects need to be elucidated. The purpose of this study is to determine, whether diet composition of carbohydrate affects the glycogen stores in the liver and affects the glucose response of glucagon during hypoglycaemia. HYPOTHESIS: In patients with type 1 diabetes, the glucose response of a single bolus of low-dose glucagon is not associated with diet carbohydrate content. AIM: The aim is to investigate how one week of high- compared to low-carbohydrate diet influence the glycaemic response of low-dose glucagon in patients with insulin pump treated type 1 diabetes. The secondary aim is to investigate how two dietary intervention weeks differ in the incidence of hypoglycaemia, postprandial hyperglycaemia, and daily glucose excursions. DESIGN:A non-blinded two-way cross-over, randomized study will be conducted. After participants have given an informed consent, they will go through four steps: 1) screening visit 2) Run-in period, 3) first meal intervention for one week finalizing with one study visit and 4) second meal intervention for one week finalizing with another study visit.

Official Title
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Glucagon Efficiency After High and Low Carbohydrate Diet

Conditions
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Type 1 Diabetes, Hypoglycemia

Intervention / Treatment
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* Dietary Supplement: High carbohydrate intake
* Dietary Supplement: Low carbohydrate intake


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 - 70 years T1D ≥ 3 year BMI 20-27 kg/m2 CSII ≥ 1 year HbA1c < 69 mmol/mol (8.5 %) C-peptide negative (< 60 pmol/l) Hypoglycemia awareness (self-reported) Use of carbohydrate counting and the insulin pump bolus calculator for all meals Exclusion Criteria: Allergy or intolerance to lactose or Glucagen®(Novo Nordisk, Bagsværd, DK) Impaired renal function (eGFR < 60 ml/min/1.73m2) Liver disease with ALAT > 2.5 times the upper limit of the reference interval Use of anti-diabetic medicine (other than insulin), corticosteroids or other drugs affecting glucose metabolism during the study period or within 30 days prior to study start Known or suspected alcohol or drug abuse Other concomitant medical or psychological condition that according to the investigator's assessment makes the patient unsuitable for study participation Females who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods. Inability to understand the patient information and to give informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: High carbohydrate diet<br>high carbohydrate intake | Dietary Supplement: Low carbohydrate intake<br>* Carbohydrate intake > 250 gram<br>|
| Active Comparator: Low carbohydrate diet<br>low carbohydrate intake | Dietary Supplement: High carbohydrate intake<br>* Carbohydrate intake < 50 gram<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incremental area under the glucose curve |  | 0-240 minutes | 
| Peak glucose value |  | within 240 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucagon concentration | Blood samples | 0-240 min. | 
| Insulin concentration | Blood samples | 0-240 min. | 
| Triglycerides concentration | Blood samples | 0-240 min. | 
| Katekolamine concentration | Blood samples | 0-240 min. | 
| Ketone bodies concentration | Blood samples | 0-240 min. | 
| Free fatty acids concentration |  | 0-240 min. | 
| Nausea | Visual analog scale | 0-240 min. | 
| Headache | Visual analog scale | 0-240 min. | 
| Hypoglycemia symptoms | Visual analog scale | 0-240 min. | 
| Vomit | Occurence | 0-240 min. | 
| Plasma glucose variation | A continuous glucose monitor register daily glucose variation levels for two weeks. | Two weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glucagon, Carbohydrate diet