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Muscle Oxygenation, Type 1 Diabetes, and Glycated Hemoglobin (OXYDIAB)

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ClinicalTrials.gov Identifier: NCT02051504
Recruitment Status : Completed
First Posted : January 31, 2014
Last Update Posted : September 13, 2016
Sponsor:
Information provided by (Responsible Party):
University Hospital, Lille

Brief Summary:
Most of the studies concerning aerobic fitness in Type 1 diabetic patients noted a relationship between impaired aerobic fitness and high glycated haemoglobin (HbA1c) levels, reflecting poor long term glycaemic control. To explain this relationship, the indirect effect of chronically high blood glucose levels on cardiovascular complications - and hence on exercise cardiovascular adaptations - are often mentioned. However, one could wonder if HbA1c could also have a direct impact on aerobic fitness patients with Type 1 diabetes. Haemoglobin glycation may increase its O2 affinity, thus limiting the O2 availability at the muscular level and impairing maximal aerobic power. Moreover, chronic hyperglycaemia might have deleterious effect on muscle mitochondrial capacity to use O2. The aim of this study is to assess the effect of Type 1 diabetes and of HbA1c level on muscular oxygen delivery and use and hence on aerobic fitness.

Condition or disease Intervention/treatment
Type 1 Diabetes Behavioral: Incremental maximal exercise Dietary Supplement: Oral Glucose Tolerance Test Procedure: Muscle biopsy Procedure: Combined DLCO-DLNO Procedure: Dual energy X-ray absorptiometry Procedure: Accelerometry over one week Other: Questionnaires

Detailed Description:

The current study aims at assessing the impact of Type 1 diabetes and HbA1c on muscle oxygen delivery and on muscle mitochondrial capacity. Our hypothesis is that these both steps of the oxygen cascade might be involved in the aerobic fitness impairment usually observed in poor-controlled patients.

Adults with Type 1 diabetes, aged 18-40 years, without microvascular and macrovascular diabetic complications, will be recruited among patients that regularly attend the unit of diabetology of the University Hospital of Lille and the regional hospital of Roubaix. They will be separated into 2 groups according to their glycaemic control at entrance in the study (HbA1c < 7%, HbA1c > 8%). Subsequently, two healthy control groups (checked by an OGTT) will be selected to strictly match the patients with Type 1 diabetes (age, sex, BMI, number of hours of physical activity per week, tobacco smoking). This is a cross-sectional study including 4 groups.

On their first visit, after the determination of HbA1c, all the subjects will perform at rest a DLCO/DLNO. Then they will realise an incremental exercise test to exhaustion on an electromagnetic cycle ergometer. Non-invasive measures will be performed throughout the exercise test, including gas exchange parameters (and maximal oxygen uptake), muscular and brain oxygenation (Near Infra Red Spectroscopy at vastus lateralis muscle and at prefrontal cortex). A blood sample from an arterialised ear-lobe will be taken at rest and exhaustion to determine O2 haemoglobin saturation, arterial partial pressure in O2 and CO2, haemoglobin concentration, hematocrit, and bicarbonates. Blood, from a catheter in a superficial cubital vein, will also be taken at rest, at a precise time during the exercise and immediately after the exercise to measure potential of hydrogen, bicarbonates, haemoglobin concentration, hematocrit, erythrocyte 2,3-diphosphoglycerate, and other blood markers of metabolic and hormonal adaptations to exercise. The subjects will also fill in questionnaires.

On a second visit, in a fasting state, the subjects will have a muscle biopsy at vastus lateralis using a specific needle (less than 150mg) in order to assess mitochondrial respiration capacity and endocannabinoid system activity. A venous blood sampling will allow analysing other health markers (lipid profile, insulin resistance...).

On another visit, the subjects will have a measure of body composition by Dual energy X-ray Absorptiometry and skinfold thickness.

They will also wear an accelerometer over one week and fill in a diet questionnaire over 3 days.


Study Type : Observational
Actual Enrollment : 79 participants
Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Impact of Type 1 Diabetes and Glycated Haemoglobin Levels on Oxygen Delivery and Release to Active Muscle During Exercise and on Muscle Oxidation Capacity - Possible Impact on Aerobic Fitness
Study Start Date : March 2010
Actual Primary Completion Date : November 2013
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Type 1 diabetes, HbA1c <7%

Patients with Type 1 diabetes and adequate glycemic control: HbA1c <7% at the entrance in the study.

Intervention:

Incremental maximal exercise Near-Infra Red-Spectroscopy at vastus lateralis and pre-frontal cortex (during exercise) Gas exchanges (VO2, VCO2) during exercise Combined DLCO/DLNO (at rest) Venous and arterialised blood sampling (rest and exercise) Muscle biopsy at the vastus lateralis (rest) Diet questionnaire, quality-of-life questionnaires, physical activity questionnaires Accelerometry over one week Dual energy X-ray Absorptiometry

Behavioral: Incremental maximal exercise
The exercise test starts 2-4h after a standardised breakfast. After a 2-min resting period sitting on the cycle ergometer (Excalibur Sport, Lode B.V, Medical Technology, Groningen, Netherlands), the test starts at 30 watts with a 20 watts increment every 2min until exhaustion.

Procedure: Muscle biopsy
A sample of vastus lateralis (less than 150mg) is taken with a specific needle under local anesthesia.

Procedure: Combined DLCO-DLNO
Lung carbon monoxide and nitric oxide diffusion capacities are assessed at rest in a sitting position.

Procedure: Dual energy X-ray absorptiometry
Body composition is measured using dual energy X-ray absorptiometry at rest.

Procedure: Accelerometry over one week
The subjects wear an uniaxial accelerometer over one week to assess their usual physical activity level

Other: Questionnaires
Diet questionnaire, quality-of-life questionnaires, physical activity questionnaires

Type 1 diabetes, HbA1c >8%

Patients with Type 1 diabetes and inadequate glycemic control: HbA1c >8% at the entrance in the study.

Intervention:

Incremental maximal exercise Near-Infra Red-Spectroscopy at vastus lateralis and pre-frontal cortex (during exercise) Gas exchanges (VO2, VCO2) during exercise Combined DLCO/DLNO (at rest) Venous and arterialised blood sampling (rest and exercise) Muscle biopsy at the vastus lateralis (rest) Diet questionnaire, quality-of-life questionnaires, physical activity questionnaires Accelerometry over one week Dual energy X-ray Absorptiometry

Behavioral: Incremental maximal exercise
The exercise test starts 2-4h after a standardised breakfast. After a 2-min resting period sitting on the cycle ergometer (Excalibur Sport, Lode B.V, Medical Technology, Groningen, Netherlands), the test starts at 30 watts with a 20 watts increment every 2min until exhaustion.

Procedure: Muscle biopsy
A sample of vastus lateralis (less than 150mg) is taken with a specific needle under local anesthesia.

Procedure: Combined DLCO-DLNO
Lung carbon monoxide and nitric oxide diffusion capacities are assessed at rest in a sitting position.

Procedure: Dual energy X-ray absorptiometry
Body composition is measured using dual energy X-ray absorptiometry at rest.

Procedure: Accelerometry over one week
The subjects wear an uniaxial accelerometer over one week to assess their usual physical activity level

Other: Questionnaires
Diet questionnaire, quality-of-life questionnaires, physical activity questionnaires

Healthy controls, Groupe 1

Healthy controls for patients with Type 1 diabetes and adequate glycemic control matched on age, sex, body composition and physical activity level.

Intervention:

Oral Glucose Tolerance Test Incremental maximal exercise Near-Infra Red-Spectroscopy at vastus lateralis and pre-frontal cortex (during exercise) Gas exchanges (VO2, VCO2) during exercise Combined DLCO/DLNO (at rest) Venous and arterialised blood sampling (rest and exercise) Muscle biopsy at the vastus lateralis (rest) Diet questionnaire, quality-of-life questionnaires, physical activity questionnaires Accelerometry over one week Dual energy X-ray Absorptiometry

Behavioral: Incremental maximal exercise
The exercise test starts 2-4h after a standardised breakfast. After a 2-min resting period sitting on the cycle ergometer (Excalibur Sport, Lode B.V, Medical Technology, Groningen, Netherlands), the test starts at 30 watts with a 20 watts increment every 2min until exhaustion.

Dietary Supplement: Oral Glucose Tolerance Test
The subjects arrive after an overnight fast and have a 75g Glucose Oral Charge.

Procedure: Muscle biopsy
A sample of vastus lateralis (less than 150mg) is taken with a specific needle under local anesthesia.

Procedure: Combined DLCO-DLNO
Lung carbon monoxide and nitric oxide diffusion capacities are assessed at rest in a sitting position.

Procedure: Dual energy X-ray absorptiometry
Body composition is measured using dual energy X-ray absorptiometry at rest.

Procedure: Accelerometry over one week
The subjects wear an uniaxial accelerometer over one week to assess their usual physical activity level

Other: Questionnaires
Diet questionnaire, quality-of-life questionnaires, physical activity questionnaires

Healthy controls, Group 2

Healthy controls for patients with Type 1 diabetes and inadequate glycemic control matched on age, sex, body composition and physical activity level.

Intervention:

Oral Glucose Tolerance Test Incremental maximal exercise Near-Infra Red-Spectroscopy at vastus lateralis and pre-frontal cortex (during exercise) Gas exchanges (VO2, VCO2) during exercise Combined DLCO/DLNO (at rest) Venous and arterialised blood sampling (rest and exercise) Muscle biopsy at the vastus lateralis (rest) Diet questionnaire, quality-of-life questionnaires, physical activity questionnaires Accelerometry over one week Dual energy X-ray Absorptiometry

Behavioral: Incremental maximal exercise
The exercise test starts 2-4h after a standardised breakfast. After a 2-min resting period sitting on the cycle ergometer (Excalibur Sport, Lode B.V, Medical Technology, Groningen, Netherlands), the test starts at 30 watts with a 20 watts increment every 2min until exhaustion.

Dietary Supplement: Oral Glucose Tolerance Test
The subjects arrive after an overnight fast and have a 75g Glucose Oral Charge.

Procedure: Muscle biopsy
A sample of vastus lateralis (less than 150mg) is taken with a specific needle under local anesthesia.

Procedure: Combined DLCO-DLNO
Lung carbon monoxide and nitric oxide diffusion capacities are assessed at rest in a sitting position.

Procedure: Dual energy X-ray absorptiometry
Body composition is measured using dual energy X-ray absorptiometry at rest.

Procedure: Accelerometry over one week
The subjects wear an uniaxial accelerometer over one week to assess their usual physical activity level

Other: Questionnaires
Diet questionnaire, quality-of-life questionnaires, physical activity questionnaires




Primary Outcome Measures :
  1. Maximal oxygen uptake [ Time Frame: Participants will perform the incremental maximal exercise on visit 1, one week minimum and 8 weeks maximum after their inclusion in the protocol ]
    Incremental maximal exercise with gas exchange measure


Secondary Outcome Measures :
  1. Arterial oxygen content during maximal exercise [ Time Frame: Prior to the incremental maximal exercise on visit 1, and immediately after the incremental maximal exercise on visit 1. ]
    measured in ear-lobe arterialised capillary samples

  2. Oxyhemoglobin dissociation at active muscle during maximal exercise [ Time Frame: On visit 1, continuously during the incremental maximal exercise ]
    Deoxyhemoglobin and total hemoglobin assessed at vastus lateralis by Near Infrared Spectroscopy

  3. Mitochondrial respiration capacity of vastus lateralis muscle [ Time Frame: Participants will have a muscle biopsy on visit 2, performed 3 days minimum and 32 weeks maximum after their visit 1. ]
    Vastus lateralis muscle sample is obtained by the percutaneous technique after local anesthesia. The mitochondrial respiration is then studied in situ in saponin-skinned fibers.

  4. Prefrontal cortex oxygenation during exercise [ Time Frame: On visit 1, continuously during the incremental maximal exercise ]
    Total hemoglobin and oxyhemoglobin are assessed at the left prefrontal cortex using Near-Infrared Spectroscopy.


Other Outcome Measures:
  1. Other factors than hemoglobin glycation that could influence arterial oxygen content [ Time Frame: Prior to the incremental maximal exercise on visit 1 ]
    Lung capillary carbon monoxide and nitric oxide diffusion capacities (DLCO, DLNO)

  2. Other factors able to modify the oxyhemoglobin dissociation curve [ Time Frame: Prior to the incremental maximal exercise on visit 1, and immediately after the incremental maximal exercise on visit 1. ]
    venous erythrocyte 2,3-diphosphoglycerate, arterialised capillary potential of hydrogen oxygen partial pressure, carbon dioxide partial pressure

  3. Mechanisms possibly involved in muscle mitochondrial dysfunctions [ Time Frame: Prior to the incremental maximal exercise on visit 1, and immediately after the incremental maximal exercise on visit 1. Prior to the muscle biopsy on visit 2. ]
    oxidative stress (blood oxidative and antioxidant markers at rest and in response to maximal exercise), endocannabinoid system activity

  4. Other health markers in link with physical activity levels and aerobic fitness [ Time Frame: Prior to the incremental maximal exercise on visit 1, and immediately after the incremental maximal exercise on visit 1. Prior to the muscle biopsy on visit 2. ]
    Lipid profile (HDL-C, LDL-C, apolipoprotein A1, apolipoprotein B, lipoprotein a, ...) Insulin resistance markers (blood ghrelin, adiponectin, leptin...)

  5. Blood metabolic and hormonal responses to exercise [ Time Frame: Prior to the incremental maximal exercise on visit 1, and immediately after the incremental maximal exercise on visit 1. ]
    Free fatty acids, glycerol, glucose, insulin, catecholamines, glucagon, cortisol, insulin-like growth factor 1, brain-derived neurotrophic factor...

  6. Body composition [ Time Frame: Prior to incremental maximal exercise on visit 1 ]
    Dual energy X-ray Absorptiometry, skinfold thickness, waist and hip circumferences


Biospecimen Retention:   Samples With DNA
Whole blood, plasma, serum, and skeletal muscle (vastus lateralis) samples


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

The two groups of patients with Type 1 diabetes are recruited from primary care clinics (university hospital of Lille and hospital of Roubaix, France) among patients with Type 1 diabetes for more than 1 year and free from micro and macrovascular complications.

Healthy participants are selected from a list (n=250) drawn up from patients' friends and contacts. Each healthy control is chosen to strictly match a patient with type 1 diabetes according to gender, age, physical activity levels, and tobacco status.

Criteria

Inclusion Criteria:

  • Patients with Type 1 diabetes (duration of Type 1 diabetes > 1 year and < 20 years)
  • Healthy subjects

Exclusion Criteria:

Exclusion Criteria for patients with Type 1 diabetes:

  • Maturity onset diabetes of the young, mitochondrial diabetes, Type 2 diabetes
  • Macro or microvascular complications of diabetes

Exclusion Criteria for healthy controls :

• Diabetes (Glycaemia > 11 mmol/L two hours after the OGTT)

Exclusion Criteria for all subjects :

  • Obesity (Body Mass Index > 30 kg/m2)
  • Contra-indication to maximal exercise
  • Pregnant or breast-feeding women
  • Other chronic disease than diabetes
  • Muscle or articular problems

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02051504


Locations
France
CHRU Lille
Lille, France, 59037
Sponsors and Collaborators
University Hospital, Lille
Investigators
Study Director: Elsa HEYMAN, PHD EA4488 'Physical activity, Muscle, Health
Principal Investigator: Pierre FONTAINE, MD-PHD CHRU Lille

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT02051504     History of Changes
Other Study ID Numbers: 2009_12
2009-A00746-51. ( Other Identifier: ID-RCB number, AFSSAPS )
First Posted: January 31, 2014    Key Record Dates
Last Update Posted: September 13, 2016
Last Verified: September 2016

Keywords provided by University Hospital, Lille:
Type 1 diabetes
Glycated hemoglobin
Muscle Oxygenation
Exercise
Maximal Oxygen uptake
Mitochondrial respiration
Endocannabinoid system
Oxidative stress

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases