Impact of Physical Activity on Blood Glucose Stability and Energy Stores in Individuals With Type 1 Diabetes

Type 1 Diabetes Mellitus Clinical Trial

— CARBEX1  

Official title:

Exercise-related Fuel Metabolism and Glucose Stability in Individuals With Type 1 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02068638
• Other study ID #: 001/14
• Secondary ID: 320030_149321/11
• Status: Completed
• Phase: N/A
• First received: February 18, 2014
• Last updated: August 9, 2016
• Start date: February 2014
• Est. completion date: July 2016

Study information

• Verified date: August 2016
• Source: University Hospital Inselspital, Berne
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Ethikkommission
• Study type: Interventional

Clinical Trial Summary

Whereas physical activity clearly results in improvements in glycemic control in type 2 diabetes, in individuals with type 1 diabetes (T1DM) the impact of exercise on blood sugar control is more complex. In type 1 diabetes T1DM the inability to reduce exogenous insulin levels during exercise is a key factor that contributes to an increased risk of exercise-induced hypoglycemia. Since rapid adaptation of insulin dosage may be especially difficult in patients on a multiple daily injection regimen, alternative strategies are required to improve exercise-associated glucose stability. There is increasing evidence that the combination of steady state continuous low to moderate intensity exercise with short bursts of high intensity exertion (eg in the form of sprints) is an effective, well tolerated, novel strategy to prevent exercise-related hypoglycemia. A further promising option to stabilize blood sugar levels during and after exercise may be the ingestion of fructose in addition to glucose in form of a sport drink.

Description:

Background

Regular physical activity enhances insulin sensitivity in both healthy subjects and patients with diabetes mellitus. However, while the effects of physical activity on glucose control are undoubtedly beneficial in patients with type 2 diabetes, exercise can cause major disturbances in blood glucose levels in type 1 diabetic individuals. Hypoglycemia is a common complication in patients with T1DM engaging in endurance activities such as running and cycling. So far there are limited strategies suggested to improve exercise-related blood sugar self-management. Current recommendations focus on variation in timing and dosage of insulin administration and adjustments in carbohydrate intake. Since rapid adaptation of insulin dosage may be difficult, alternative strategies to improve exercise-related glucose stability are required. Increasing evidence suggests that intermittent high intensity exercise (IHE), by triggering a counterregulatory hormone response, may counter-balance the risk of exercise-associated hypoglycemia. However, previous studies investigating IHE in T1DM were limited by heterogeneous study populations, comparably short exercise protocols, and deficits in standardization procedures. In addition, a comprehensive assessment of the underlying fuel metabolism has not been performed so far. As a consequence, the results remain controversial and their interpretation as well as applicability are restricted.

A further alternative strategy to maintain stable glycemia during exercise may be deduced from recent studies in non-diabetic individuals suggesting that the combined ingestion of fructose and glucose during exercise provides the liver with an increased amount of gluconeogenic precursors, thereby reducing consumption of endogenous glycogen stores.Moreover, conversion of fructose into glucose and lactate may provide constant and efficient fuel for working muscles. However, studies assessing the impact of fructose ingestion during exercise in patients with T1DM have not been performed so far.

Objective

The investigators aim to assess the impact of two novel non-pharmaceutical and easily feasible approaches on exercise-related blood glucose stability and its underlying exercise-related fuel metabolism in patients with T1DM.

Substudy A will assess the influence on exercise-related glycemia and fuel metabolism of an IHE protocol compared to an iso-energetic continuous exercise (CONT). It will be investigated whether individuals reach more stable blood glucose levels when engaging in IHE compared to CONT.

Substudy B will investigate whether fueling the patients with a mixed oral 1:1 glucose-fructose carbohydrate solution will maintain glucose values within a more stable range when compared to carbohydrate supplementation by glucose alone.

Methods

Blood glucose levels, counterregulatory hormones, metabolites such as lactate and free fatty acids as well as inflammatory biomarkers will be assessed by regular blood samplings. By means of oral and intravenously given stable isotopes (U-13 C glucose and 2H glucose) exercise-related glucose kinetics will be investigated. Exercise-induced glycogen consumption will be measured using magnetic resonance spectroscopy technology. Late glycemic excursions will be recorded by continuous glucose monitoring systems.

In order to validate 13C magnetic resonance spectroscopy (MRS) measurement of hepatic and myocellular glycogen content a pre-study involving 10 patients and an equal number of matched healthy controls will be performed (validation and reproducibility study).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Male

• Aged 18 to 35 years

• Diabetes mellitus duration for at least 5 years

• No change in insulin regimen for at least 3 months prior to the study

• Under acceptable to good metabolic control

• Normal insulin sensitivity

• Regular physical activity

• BMI in the range of 18-25 kg/m2

• Written informed consent

Exclusion Criteria

• Diabetes-related complications (macro and microvascular)

• Anemia (hemoglobin concentration <130g/l)

• Abnormal thyroid function

• Dyslipidemia

• Major depression, psychosis and other severe personality disorders, claustrophobia

• Active neoplasia

• Contraindications to exposure to a 3 T magnetic field

• Abnormal liver or renal function

• Smoking, drug abuse, or daily alcohol consumption >60g

• Participation in another study

• Medication other than insulin

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Carbohydrate Metabolism
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Exercise
• Hypoglycemia
• Type 1 Diabetes Mellitus

Intervention

Procedure:
• IHE first, CONT second
IHE: intermittent high intensity exercise: integration of 10 s maximal sprints every 10 minutes in a continuous low to moderate intensity exercise of 90 minutes. CONT (occurring after a washout period of 2-8 weeks): continuous moderate intensity exercise of 90 minutes
• CONT first, IHE second
CONT: continuous moderate intensity exercise of 90 minutes. IHE (occurring after a washout period of 2-8 weeks): intermittent high intensity exercise: integration of 10 s maximal sprints every 10 minutes in a continuous low to moderate intensity exercise of 90 minutes
• GLU first, GLU-FRU second
: ingestion of a 6% carbohydrate solution (consisting of 90 g glucose dissolved in 1500 ml tap water) over a continuous moderate exercise of 90 minutes. GLU FRU (occurring after a washout period of 2-8 weeks): ingestion of a 12% carbohydrate solution (consisting of 90 g glucose + 90 g fructose dissolved in 1500 ml tap water) over a continuous moderate exercise of 90 minutes
• GLU-FRU first, GLU second
GLU-FRU : ingestion of a 12% carbohydrate solution (consisting of 90 g glucose + 90 g fructose dissolved in 1500 ml tap water) over a continuous moderate exercise of 90 minutes. GLU (occurring after a washout period of 2-8 weeks): : ingestion of a 6% carbohydrate solution (consisting of 90 g glucose dissolved in 1500 ml tap water) over a continuous moderate exercise of 90 minutes.

Locations

Country	Name	City	State
Switzerland	Division of Endocrinology, Diabetes and Clinical Nutrition, Bern University Hospital	Bern

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne	University of Bern, University of Lausanne

Country where clinical trial is conducted

Switzerland, 

References & Publications (8)

Bussau VA, Ferreira LD, Jones TW, Fournier PA. A 10-s sprint performed prior to moderate-intensity exercise prevents early post-exercise fall in glycaemia in individuals with type 1 diabetes. Diabetologia. 2007 Sep;50(9):1815-8. Epub 2007 Jun 22. — View Citation

Bussau VA, Ferreira LD, Jones TW, Fournier PA. The 10-s maximal sprint: a novel approach to counter an exercise-mediated fall in glycemia in individuals with type 1 diabetes. Diabetes Care. 2006 Mar;29(3):601-6. — View Citation

Guelfi KJ, Jones TW, Fournier PA. The decline in blood glucose levels is less with intermittent high-intensity compared with moderate exercise in individuals with type 1 diabetes. Diabetes Care. 2005 Jun;28(6):1289-94. — View Citation

Guelfi KJ, Ratnam N, Smythe GA, Jones TW, Fournier PA. Effect of intermittent high-intensity compared with continuous moderate exercise on glucose production and utilization in individuals with type 1 diabetes. Am J Physiol Endocrinol Metab. 2007 Mar;292( — View Citation

Iscoe KE, Riddell MC. Continuous moderate-intensity exercise with or without intermittent high-intensity work: effects on acute and late glycaemia in athletes with Type 1 diabetes mellitus. Diabet Med. 2011 Jul;28(7):824-32. doi: 10.1111/j.1464-5491.2011. — View Citation

Jenni S, Oetliker C, Allemann S, Ith M, Tappy L, Wuerth S, Egger A, Boesch C, Schneiter P, Diem P, Christ E, Stettler C. Fuel metabolism during exercise in euglycaemia and hyperglycaemia in patients with type 1 diabetes mellitus--a prospective single-blin — View Citation

Lecoultre V, Benoit R, Carrel G, Schutz Y, Millet GP, Tappy L, Schneiter P. Fructose and glucose co-ingestion during prolonged exercise increases lactate and glucose fluxes and oxidation compared with an equimolar intake of glucose. Am J Clin Nutr. 2010 N — View Citation

Stettler C, Jenni S, Allemann S, Steiner R, Hoppeler H, Trepp R, Christ ER, Zwahlen M, Diem P. Exercise capacity in subjects with type 1 diabetes mellitus in eu- and hyperglycaemia. Diabetes Metab Res Rev. 2006 Jul-Aug;22(4):300-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Amount of exogenous glucose required to maintain glycemia within a range between 7-10mM		30 minutes (last 30 minutes of 90 min exercise period)	Yes
Secondary	Exercise - related glycogen consumption		90 minutes	No
Secondary	Glucose kinetics	Rate of glucose appearance and disappearance	180 minutes	No
Secondary	Counterregulatory hormones, metabolites, and inflammatory response		300 minutes	No
Secondary	Spiroergometric parameters	CO2 and O2 production, RER	180 minutes	No
Secondary	Pre- and post-exercise glycemic excursions		72 h pre-exercise and 72 h post-exercise respectively	No
Secondary	Heart rate variability		90 minutes	No