Fructose in Exercising Individuals With Type 1 Diabetes Using Insulin Degludec (FruDeg)

Fructose to Reduce Exercise-associated Hypoglycaemia in Individuals With Type 1 Diabetes Treated With Insulin Degludec: Questioning a Paradigm and Offering a Novel Strategy

To determine and compare the time-to-hypoglycaemia (defined as plasma glucose <3.9mmol/L) in individuals with type 1 diabetes treated with ultra-Long acting insulin degludec during aerobic exercise with or without prior ingestion of a single oral fructose load.

Study Overview

• Status: Completed
• Conditions: Diabetes Complications; Type 1 Diabetes Mellitus
• Intervention / Treatment: Dietary supplement: Fructose; Other: Plain water

Detailed Description

Glycaemic control remains complex and demanding during exercise for type 1 diabetes (T1D) patients. Traditional treatment guidelines for exercise emphasizing the reduction of insulin doses and/or ingestion of additional carbohydrates are of limited applicability for patients treated with ultra-long acting basal insulin analogues. Dose reductions may require two to three days for modern basal insulin analogues in order to achieve an adapted steady state, hereby increasing the risk of inadequate insulin-following exercise. If T1D patients engage in recreational exercise - as recommended by every international treatment guideline - current treatment strategies may simply not be sufficient.

As a consequence for patients treated with modern basal insulin analogues, it seems more adequate not to modify insulin doses but to apply alternative strategies for recreational exercise. The ingestion of fructose, an insulin-independent carbohydrate, which increases lipid oxidation but attenuates the dependency on carbohydrates may offer a novel strategy. Up to date, only preliminary data for fructose have been produced regarding clinical effectiveness and underlying mechanisms in the prevention of hypoglycaemia. The present comprehensive study aims to investigate the clinical efficacy, feasibility, and safety of a pre-exercise oral fructose load without modification of insulin degludec in T1D patients.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Division of Endocrinology, Diabetes and Clinical Nutrition, Bern University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Type 1 diabetes as defined by the World Health Organization (WHO) for at least 1 year or confirmed negative C-peptide (<100pmol/l with concomitant blood glucose >4 mmol/l)
• Male subjects aged between 18-45 years
• HbA1c <8.0% (64mmol/mol) based on analysis from the central laboratory unit of the University Hospital Bern.
• Basal/Bolus-insulin regimen with insulin degludec for at least 3 months, with good knowledge of insulin self-management
• Regular physical activity (at least 30 min of moderate exercise 3 times weekly)
• Written informed consent

Exclusion Criteria:

• Relevant diabetic complications as judged by the investigator
• Total daily insulin dose >2 IU/kg/day
• Hypoglycaemia unawareness (Gold score > 4) or any episode of severe hypoglycaemia as defined by the American Diabetes Association within the last 6 months
• Physical or psychological disease likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator
• Current treatment with drugs known to interfere with metabolism, e.g. systemic corticosteroids, statins etc.
• Known fructose-intolerance or malabsorption
• Known allergy to one of the study drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fructose in water first, water only second; Intake of 20 g of fructose dissolved in 200 ml of tap water at first visit; intake of 200 ml of tap water at second visit	Dietary supplement: Fructose; Intake of 20 g of fructose dissolved in 200 ml of tap water within 5 minutes 30 minutes prior to exercise.; Other: Plain water; Intake of 200 ml of tap water within 5 minutes 30 minutes prior to exercise.
Experimental: Water only first, Fructose in water second; Intake of 200 ml of tap water at first visit; intake of 200 ml of 20 g of fructose dissolved in 200 ml of tap water at second visit	Dietary supplement: Fructose; Intake of 20 g of fructose dissolved in 200 ml of tap water within 5 minutes 30 minutes prior to exercise.; Other: Plain water; Intake of 200 ml of tap water within 5 minutes 30 minutes prior to exercise.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time (in minutes) to hypoglycaemia (plasma glucose <3.9mmol/l)	The development of hypoglycaemia will be determined by repeated measurement of plasma glucose.	From time point 0 minutes (initiation of exercise) to time point 60 minutes (completion of exercise) or development of hypoglycaemia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose levels before exercise	Plasma glucose will be measured repeatedly every 5 minutes	Time point -30 minutes until time point 0 minutes (initiation of exercise)
Glucose levels during exercise	Plasma glucose will be measured repeatedly every 5 minutes	From time point 0 minutes until time point 60 minutes (completion of exercise) or development of hypoglycaemia
Glucose levels after exercise	Plasma glucose will be measured repeatedly every 5 minutes	From time point 0 minutes until time point 90 minutes
Lactate levels before exercise	Lactate will be measured repeatedly every 5 minutes	From time point -30 minutes until time point 0 minutes (initiation of exercise)
Lactate levels during exercise	Lactate will be measured repeatedly every 5 minutes	From time point 0 minutes until time point 60 minutes (completion of exercise) or development of hypoglycaemia
Lactate levels after exercise	Lactate will be measured repeatedly every 5 minutes	From time point 0 minutes until time point 90 minutes
Insulin levels before exercise	Lactate will be measured repeatedly every 15 minutes	Time point -30 minutes until time point 0 minutes (initiation of exercise)
Insulin levels during exercise	Insulin will be measured repeatedly every 15 minutes	From time point 0 minutes until time point 60 minutes (completion of exercise) or development of hypoglycaemia
Insulin levels after exercise	Insulin will be measured repeatedly every 15 minutes	From time point 0 minutes until time point 150 minutes
Heart rate before exercise	Heart rate will be measured using an electro-cardio-gramme	Time point -30 minutes until time point 0 minutes (initiation of exercise)
Heart rate during exercise	Heart rate will be measured using an electro-cardio-gramme	From time point 0 minutes until time point 60 minutes (completion of exercise) or development of hypoglycaemia
Oxygen consumption before exercise	Oxygen consumption will be measured via spirometry	Between 15 minutes and 5 minutes before initiation of exercise
Oxygen consumption during exercise	Oxygen consumption will be measured via spirometry	Between 15 minutes and 20 minutes during exercise
Carbon dioxide production before exercise	Carbon dioxide production will be measured via spirometry	Between 15 minutes and 5 minutes before initiation of exercise
Carbon dioxide production during exercise	Carbon dioxide production will be measured via spirometry	Between 15 minutes and 20 minutes during exercise

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Investigators: Principal Investigator: Christoph Stettler, MD, Inselspital, Bern University Hospital, University of Bern

Publications and helpful links

General Publications

• Kosinski C, Herzig D, Laesser CI, Nakas CT, Melmer A, Vogt A, Vogt B, Laimer M, Bally L, Stettler C. A Single Load of Fructose Attenuates the Risk of Exercise-Induced Hypoglycemia in Adults With Type 1 Diabetes on Ultra-Long-Acting Basal Insulin: A Randomized, Open-Label, Crossover Proof-of-Principle Study. Diabetes Care. 2020 Sep;43(9):2010-2016. doi: 10.2337/dc19-2250. Epub 2020 Jun 26.

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2019
• Primary Completion (Actual): September 6, 2019
• Study Completion (Actual): September 8, 2019

Study Registration Dates

• First Submitted: April 6, 2018
• First Submitted That Met QC Criteria: April 6, 2018
• First Posted (Actual): April 13, 2018

Study Record Updates

• Last Update Posted (Actual): September 20, 2019
• Last Update Submitted That Met QC Criteria: September 19, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Type 1 Diabetes, Fructose, Exercise, Hypoglycaemia, Degludec
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Complications
• Other Study ID Numbers: FruDeg

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No