Muscle Oxygenation, Type 1 Diabetes, and Glycated Hemoglobin

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.

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