Muscle Oxygenation, Type 1 Diabetes, and Glycated Hemoglobin

NCT02051504 | Completed DMC

• 2 other identifiers: 2009_122009-A00746-51.
• Study Type: observational
• Target: 79
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 1 Diabetes

Keywords

Type 1 diabetes; Glycated hemoglobin; Muscle Oxygenation; Exercise; Maximal Oxygen uptake; Mitochondrial respiration; Endocannabinoid system; Oxidative stress

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Arterial oxygen content during maximal exercise

  Prior to the incremental maximal exercise on visit 1, and immediately after the incremental maximal exercise on visit 1.

• Oxyhemoglobin dissociation at active muscle during maximal exercise

  On visit 1, continuously during the incremental maximal exercise

• Mitochondrial respiration capacity of vastus lateralis muscle

  Participants will have a muscle biopsy on visit 2, performed 3 days minimum and 32 weeks maximum after their visit 1.

• Prefrontal cortex oxygenation during exercise

  On visit 1, continuously during the incremental maximal exercise

Other Outcomes (6)

• Other factors than hemoglobin glycation that could influence arterial oxygen content

  Prior to the incremental maximal exercise on visit 1

• Other factors able to modify the oxyhemoglobin dissociation curve

  Prior to the incremental maximal exercise on visit 1, and immediately after the incremental maximal exercise on visit 1.

• Mechanisms possibly involved in muscle mitochondrial dysfunctions

  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.

Study Arms (4)

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; Procedure: Muscle biopsy; Procedure: Combined DLCO-DLNO; Procedure: Dual energy X-ray absorptiometry; Procedure: Accelerometry over one week; Other: 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; Procedure: Muscle biopsy; Procedure: Combined DLCO-DLNO; Procedure: Dual energy X-ray absorptiometry; Procedure: Accelerometry over one week; Other: 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; 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

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; 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

Interventions

Incremental maximal exercise BEHAVIORAL

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.

Healthy controls, Group 2; Healthy controls, Groupe 1; Type 1 diabetes, HbA1c <7%; Type 1 diabetes, HbA1c >8%

Oral Glucose Tolerance Test DIETARY_SUPPLEMENT

The subjects arrive after an overnight fast and have a 75g Glucose Oral Charge.

Healthy controls, Group 2; Healthy controls, Groupe 1

Muscle biopsy PROCEDURE

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

Healthy controls, Group 2; Healthy controls, Groupe 1; Type 1 diabetes, HbA1c <7%; Type 1 diabetes, HbA1c >8%

Combined DLCO-DLNO PROCEDURE

Lung carbon monoxide and nitric oxide diffusion capacities are assessed at rest in a sitting position.

Healthy controls, Group 2; Healthy controls, Groupe 1; Type 1 diabetes, HbA1c <7%; Type 1 diabetes, HbA1c >8%

Dual energy X-ray absorptiometry PROCEDURE

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

Healthy controls, Group 2; Healthy controls, Groupe 1; Type 1 diabetes, HbA1c <7%; Type 1 diabetes, HbA1c >8%

Accelerometry over one week PROCEDURE

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

Healthy controls, Group 2; Healthy controls, Groupe 1; Type 1 diabetes, HbA1c <7%; Type 1 diabetes, HbA1c >8%

Questionnaires OTHER

Diet questionnaire, quality-of-life questionnaires, physical activity questionnaires

Healthy controls, Group 2; Healthy controls, Groupe 1; Type 1 diabetes, HbA1c <7%; Type 1 diabetes, HbA1c >8%

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

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

You may not qualify if:

• Maturity onset diabetes of the young, mitochondrial diabetes, Type 2 diabetes
• Macro or microvascular complications of diabetes
• Diabetes (Glycaemia \> 11 mmol/L two hours after the OGTT)
• 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

Sponsors & Collaborators

• University Hospital, Lille: lead

Study Sites (1)

CHRU Lille

Lille, 59037, France

Location

Related Publications (5)

• Jlali I, Heyman E, Matran R, Marais G, Descatoire A, Rabasa-Lhoret R, Touil I, Pawlak-Chaouch M, Mucci P, Fontaine P, Baquet G, Tagougui S. Respiratory function in uncomplicated type 1 diabetes: Blunted during exercise even though normal at rest! Diabet Med. 2023 May;40(5):e15036. doi: 10.1111/dme.15036. Epub 2023 Jan 10.

  PMID: 36585956 DERIVED

• Lespagnol E, Tagougui S, Fernandez BO, Zerimech F, Matran R, Maboudou P, Berthoin S, Descat A, Kim I, Pawlak-Chaouch M, Boissiere J, Boulanger E, Feelisch M, Fontaine P, Heyman E. Circulating biomarkers of nitric oxide bioactivity and impaired muscle vasoreactivity to exercise in adults with uncomplicated type 1 diabetes. Diabetologia. 2021 Feb;64(2):325-338. doi: 10.1007/s00125-020-05329-8. Epub 2020 Nov 21.

  PMID: 33219433 DERIVED

• Heyman E, Daussin F, Wieczorek V, Caiazzo R, Matran R, Berthon P, Aucouturier J, Berthoin S, Descatoire A, Leclair E, Marais G, Combes A, Fontaine P, Tagougui S. Muscle Oxygen Supply and Use in Type 1 Diabetes, From Ambient Air to the Mitochondrial Respiratory Chain: Is There a Limiting Step? Diabetes Care. 2020 Jan;43(1):209-218. doi: 10.2337/dc19-1125. Epub 2019 Oct 21.

  PMID: 31636081 DERIVED

• Tagougui S, Fontaine P, Leclair E, Aucouturier J, Matran R, Oussaidene K, Descatoire A, Prieur F, Mucci P, Vambergue A, Baquet G, Heyman E. Regional cerebral hemodynamic response to incremental exercise is blunted in poorly controlled patients with uncomplicated type 1 diabetes. Diabetes Care. 2015 May;38(5):858-67. doi: 10.2337/dc14-1792. Epub 2015 Feb 9.

  PMID: 25665816 DERIVED

• Tagougui S, Leclair E, Fontaine P, Matran R, Marais G, Aucouturier J, Descatoire A, Vambergue A, Oussaidene K, Baquet G, Heyman E. Muscle oxygen supply impairment during exercise in poorly controlled type 1 diabetes. Med Sci Sports Exerc. 2015 Feb;47(2):231-9. doi: 10.1249/MSS.0000000000000424.

  PMID: 24983346 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, plasma, serum, and skeletal muscle (vastus lateralis) samples

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Motor Activity

Interventions

Glucose Tolerance Test; Absorptiometry, Photon; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Behavior

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques; Radiography; Diagnostic Imaging; Densitometry; Photometry; Chemistry Techniques, Analytical; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Elsa HEYMAN, PHD

  EA4488 'Physical activity, Muscle, Health

  STUDY DIRECTOR

• Pierre FONTAINE, MD-PHD

  CHRU LILLE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2013
• First Posted: January 31, 2014
• Study Start: March 1, 2010
• Primary Completion: November 1, 2013
• Study Completion: December 1, 2013
• Last Updated: September 13, 2016

Record last verified: 2016-09

Locations

FR (1)