Muscle Oxygenation, Type 1 Diabetes, and Glycated Hemoglobin

Type 1 Diabetes Clinical Trial

— OXYDIAB  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02051504
• Other study ID #: 2009_12
• Secondary ID: 2009-A00746-51.
• Status: Completed
• Phase: N/A
• First received: December 20, 2013
• Last updated: September 12, 2016
• Start date: March 2010
• Est. completion date: December 2013

Study information

• Verified date: September 2016
• Source: University Hospital, Lille
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: December 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 40 Years

Eligibility

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

Study Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

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.
• Combined DLCO-DLNO
Lung carbon monoxide and nitric oxide diffusion capacities are assessed at rest in a sitting position.
• Dual energy X-ray absorptiometry
Body composition is measured using dual energy X-ray absorptiometry at rest.
• 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

Locations

Country	Name	City	State
France	CHRU Lille	Lille

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Lille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Other factors than hemoglobin glycation that could influence arterial oxygen content	Lung capillary carbon monoxide and nitric oxide diffusion capacities (DLCO, DLNO)	Prior to the incremental maximal exercise on visit 1	No
Other	Other factors able to modify the oxyhemoglobin dissociation curve	venous erythrocyte 2,3-diphosphoglycerate, arterialised capillary potential of hydrogen oxygen partial pressure, carbon dioxide partial pressure	Prior to the incremental maximal exercise on visit 1, and immediately after the incremental maximal exercise on visit 1.	No
Other	Mechanisms possibly involved in muscle mitochondrial dysfunctions	oxidative stress (blood oxidative and antioxidant markers at rest and in response to maximal exercise), endocannabinoid system activity	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.	No
Other	Other health markers in link with physical activity levels and aerobic fitness	Lipid profile (HDL-C, LDL-C, apolipoprotein A1, apolipoprotein B, lipoprotein a, ...) Insulin resistance markers (blood ghrelin, adiponectin, leptin...)	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.	No
Other	Blood metabolic and hormonal responses to exercise	Free fatty acids, glycerol, glucose, insulin, catecholamines, glucagon, cortisol, insulin-like growth factor 1, brain-derived neurotrophic factor...	Prior to the incremental maximal exercise on visit 1, and immediately after the incremental maximal exercise on visit 1.	No
Other	Body composition	Dual energy X-ray Absorptiometry, skinfold thickness, waist and hip circumferences	Prior to incremental maximal exercise on visit 1	No
Primary	Maximal oxygen uptake	Incremental maximal exercise with gas exchange measure	Participants will perform the incremental maximal exercise on visit 1, one week minimum and 8 weeks maximum after their inclusion in the protocol	No
Secondary	Arterial oxygen content during maximal exercise	measured in ear-lobe arterialised capillary samples	Prior to the incremental maximal exercise on visit 1, and immediately after the incremental maximal exercise on visit 1.	No
Secondary	Oxyhemoglobin dissociation at active muscle during maximal exercise	Deoxyhemoglobin and total hemoglobin assessed at vastus lateralis by Near Infrared Spectroscopy	On visit 1, continuously during the incremental maximal exercise	No
Secondary	Mitochondrial respiration capacity of vastus lateralis muscle	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.	Participants will have a muscle biopsy on visit 2, performed 3 days minimum and 32 weeks maximum after their visit 1.	No
Secondary	Prefrontal cortex oxygenation during exercise	Total hemoglobin and oxyhemoglobin are assessed at the left prefrontal cortex using Near-Infrared Spectroscopy.	On visit 1, continuously during the incremental maximal exercise	No