Muscle Oxygenation, Type 1 Diabetes, and Glycated Hemoglobin
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Observational

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.
    

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.
    

Intervention name(s): Incremental maximal exercise; Oral Glucose Tolerance Test; Muscle biopsy; Combined DLCO-DLNO; Dual energy X-ray absorptiometry; Accelerometry over one week; Questionnaires
Intervention type(s): Behavioral; Dietary Supplement; Procedure; Procedure; Procedure; Procedure; Other
Intervention description(s): 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.; The subjects arrive after an overnight fast and have a 75g Glucose Oral Charge.; A sample of vastus lateralis (less than 150mg) is taken with a specific needle under local anesthesia.; Lung carbon monoxide and nitric oxide diffusion capacities are assessed at rest in a sitting position.; Body composition is measured using dual energy X-ray absorptiometry at rest.; The subjects wear an uniaxial accelerometer over one week to assess their usual physical activity level; Diet questionnaire, quality-of-life questionnaires, physical activity questionnaires
Observational model: Case-Control
Time perspective: Cross-Sectional
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.
      
Biospecimen description: 
      Whole blood, plasma, serum, and skeletal muscle (vastus lateralis) samples
    
Keywords: Type 1 diabetes; Glycated hemoglobin; Muscle Oxygenation; Exercise; Maximal Oxygen uptake; Mitochondrial respiration; Endocannabinoid system; Oxidative stress