Clinical trial NCT02578498: Glucagon Efficiency After High and Low Carbohydrate Diet
Official title: Glucagon Efficiency After High and Low Carbohydrate Diet
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 1 Diabetes
Hypoglycemia
Keywords: glucagon
Carbohydrate diet
Lead sponsor: Hvidovre University Hospital
Sponsor class: OTHER
Collaborators: name: Danish Diabetes Academy
First posted: 2015-10-19
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incremental area under the glucose curve
timeFrame: 0-240 minutes
measure: Peak glucose value
timeFrame: within 240 minutes
Secondary outcomes:
measure: Glucagon concentration
timeFrame: 0-240 min.
measure: Insulin concentration
timeFrame: 0-240 min.
measure: Triglycerides concentration
timeFrame: 0-240 min.
measure: Katekolamine concentration
timeFrame: 0-240 min.
measure: Ketone bodies concentration
timeFrame: 0-240 min.
measure: Free fatty acids concentration
timeFrame: 0-240 min.
measure: Nausea
timeFrame: 0-240 min.
measure: Headache
timeFrame: 0-240 min.
measure: Hypoglycemia symptoms
timeFrame: 0-240 min.
measure: Vomit
timeFrame: 0-240 min.
measure: Plasma glucose variation
timeFrame: Two weeks
Other outcomes:
Locations:
city: Hvidovre
country: Denmark
facility: Hvidovre University Hospital
Study officials:
affiliation: Hvidovre University Hospital
name: Kirsten Nørgaard, MD, DMSc
role: STUDY_CHAIR
References:
citation: Ranjan A, Schmidt S, Damm-Frydenberg C, Steineck I, Clausen TR, Holst JJ, Madsbad S, Norgaard K. Low-Carbohydrate Diet Impairs the Effect of Glucagon in the Treatment of Insulin-Induced Mild Hypoglycemia: A Randomized Crossover Study. Diabetes Care. 2017 Jan;40(1):132-135. doi: 10.2337/dc16-1472. Epub 2016 Oct 21.