Fructose in Exercising Individuals With Type 1 Diabetes Using Insulin Degludec

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Type 1 Diabetes Mellitus, Diabetes Complications

Intervention / Treatment
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* Dietary Supplement: Fructose
* Other: Plain water


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fructose in water first, water only second<br>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<br>* Intake of 20 g of fructose dissolved in 200 ml of tap water within 5 minutes 30 minutes prior to exercise.<br>Other: Plain water<br>* Intake of 200 ml of tap water within 5 minutes 30 minutes prior to exercise.<br>|
| Experimental: Water only first, Fructose in water second<br>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<br>* Intake of 20 g of fructose dissolved in 200 ml of tap water within 5 minutes 30 minutes prior to exercise.<br>Other: Plain water<br>* Intake of 200 ml of tap water within 5 minutes 30 minutes prior to exercise.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 Diabetes, Fructose, Exercise, Hypoglycaemia, Degludec