Glucagon Efficiency After High and Low Carbohydrate Diet (HiLoCarb)

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.

Study Overview

• Status: Completed
• Conditions: Hypoglycemia; Type 1 Diabetes
• Intervention / Treatment: Dietary supplement: Low carbohydrate intake; Dietary supplement: High carbohydrate intake

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Hvidovre, Denmark, 2650
    • Hvidovre University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: High carbohydrate diet; high carbohydrate intake	Dietary supplement: Low carbohydrate intake; Carbohydrate intake > 250 gram
ACTIVE_COMPARATOR: Low carbohydrate diet; low carbohydrate intake	Dietary supplement: High carbohydrate intake; Carbohydrate intake < 50 gram

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital
• Collaborators: Danish Diabetes Academy

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (ACTUAL): March 1, 2016
• Study Completion (ACTUAL): July 1, 2016

Study Registration Dates

• First Submitted: October 14, 2015
• First Submitted That Met QC Criteria: October 15, 2015
• First Posted (ESTIMATE): October 19, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): August 16, 2016
• Last Update Submitted That Met QC Criteria: August 15, 2016
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: glucagon; Carbohydrate diet
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hypoglycemia
• Other Study ID Numbers: H-15009662