Isolated and Combined Effect of a Low Carbohydrate Diet and Exercise in Hypoxia in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to determine the effects of isolated chronic exercise in hypoxia and combined exercise in hypoxia with a low carbohydrate diet on hypoxia-induced transcription factor (HIF1-α); glycaemic control and cardiovascular risk factors in patients with type 2 diabetes.

Detailed Description
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At baseline, diet plans will be individualized and energy-content prescriptions will be constant throughout the study to maintain the isocaloric control between diets. The planned macronutrient compositions will be, 30% of energy from carbohydrates, 20% from protein and 50% from fat for low carbohydrate diet (LCD) and 30% of energy from fat, 20% from protein and 50% from carbohydrates for the low-fat diet (control diet), during the 8 weeks. Both diets emphasis on low-glycemic index foods and limited saturated fat to 10% of energy, and calculated with appropriate software. Exercise in hypoxia (at 3000m altitude, 3 sessions/week) will occur during a 8-week period intervention and all testing sessions carried out in a hypoxic chamber at Exercise Medical Center, Porto - Portugal. This chamber allows control of O2 (11-20.97%), temperature (until 50ºC), humidity (until 80%) and altitude (until 8000m). Exercise in hypoxia sessions will consist in 60 min on an ergometer (Excalibur, Lode, Netherlands) of continuous moderate and high intensity interval training, these latter considered as an efficient strategy to improve cardiorespiratory and metabolic health in patients with type 2 diabetes. Loads will be quantified according to pre-intervention testing assessments and controlled throughout each training session. All exercise testing and training sessions will be carried out at the same time of day (± 2 hours) and visits will be separated by at least 48h of recovery. Height will be measured with use of a stadiometer (SECA), waist circumference was measured by using a tape measure positioned 3 cm above the iliac crest. Body mass index (BMI), weight, fat mass (FM) and fat-free mass (FFM) were determined by using whole-body dual-energy X-ray absorptiometry (Lunar Prodigy; General Electric Corp.). Blood pressure will be measured by using an automated sphygmomanometer (Dinamap Pro; Medical Systems,Tampa, FL) and haematological adaptations will be measured by collecting a venous blood sample from a vein in the arm using a needle. A total of 3 blood samples (pre, 1h post first intervention testing and 48h post the last intervention testing) will be taken.

Official Title
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Isolated and Combined Effect of a Low Carbohydrate Diet and Chronic Exercise Exposure to Hypoxia on Glycaemic Control and Cardiovascular Risk Factors in Patients With Type 2 Diabetes

Conditions
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Carbohydrate, Hypoxia, Exercise, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Other: Exercise in normoxia
* Other: Control diet
* Other: Exercise in hypoxia
* Other: Low carbohydrate diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of type 2 diabetes for at least one year Glycosylated haemoglobin less than 10% Pharmacological regimen stabilized for at least three months Main complications of diabetes tracked and controlled (diabetic retinopathy, diabetic nephropathy, diabetic foot and main factors of cardiovascular risk) Previous participation in supervised exercise programs in the last 3 months Smoking absence in the last 6 months. Exclusion Criteria: Diagnosis of type 2 diabetes for less than a year Glycosylated haemoglobin above 10% Pharmacological regimen less than three months Main complications of diabetes (diabetic retinopathy, diabetic nephropathy, diabetic foot and main factors of cardiovascular risk) Sedentary participants Smoking participants

Ages Eligible for Study
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Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CONTROL GROUP<br>Exercise at sea level, normoxia. Control diet. | Other: Exercise in normoxia<br>* Exercise at sea level, 3 sessions per week, during a 8-week period intervention and will consist in 60 min on an ergometer, of continuous moderate and high intensity interval training. . All exercise testing and training sessions will be carried out at the same time of day (± 2 hours) and visits will be separated by at least 48h of recovery.<br>Other: Control diet<br>* Control diet: diet plans will be individualized and energy-content prescriptions will be constant throughout the study to maintain the isocaloric control between diets. The planned macronutrient compositions will be 20% of energy from fat, 20% from protein and 60% from carbohydrates for the low-fat diet during the 8 weeks. Diets emphasis on low-glycemic index foods and limited saturated fat to 10% of energy. Participants will meet individually with a dietitian two times for 8 weeks and should start the dietary intervention along with the intervention with exercise.<br>|
| Experimental: Ex. Hyp. GROUP<br>Exercise in hypoxia at 3000m altitude. Control diet. | Other: Control diet<br>* Control diet: diet plans will be individualized and energy-content prescriptions will be constant throughout the study to maintain the isocaloric control between diets. The planned macronutrient compositions will be 20% of energy from fat, 20% from protein and 60% from carbohydrates for the low-fat diet during the 8 weeks. Diets emphasis on low-glycemic index foods and limited saturated fat to 10% of energy. Participants will meet individually with a dietitian two times for 8 weeks and should start the dietary intervention along with the intervention with exercise.<br>Other: Exercise in hypoxia<br>* Exercise at 3000m altitude, 3 sessions per week, during a 8-week period intervention and will consist in 60 min on an ergometer, of continuous moderate and high intensity interval training. . All exercise testing and training sessions will be carried out at the same time of day (± 2 hours) and visits will be separated by at least 48h of recovery.<br>|
| Experimental: Ex. Hyp. + LCD GROUP<br>Exercise in hypoxia at 3000m altitude. Low carbohydrate diet. | Other: Exercise in hypoxia<br>* Exercise at 3000m altitude, 3 sessions per week, during a 8-week period intervention and will consist in 60 min on an ergometer, of continuous moderate and high intensity interval training. . All exercise testing and training sessions will be carried out at the same time of day (± 2 hours) and visits will be separated by at least 48h of recovery.<br>Other: Low carbohydrate diet<br>* Low carbohydrate diet: diet plans will be individualized and energy-content prescriptions will be constant throughout the study to maintain the isocaloric control between diets. The planned macronutrient compositions will be 40% of energy from fat, 20% from protein and 40% from carbohydrates for the low-fat diet during the 8 weeks. Diets emphasis on low-glycemic index foods and limited saturated fat to 10% of energy. Participants will meet individually with a dietitian two times for 8 weeks and should start the dietary intervention along with the intervention with exercise.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from pre- to pos intervention on glycated haemoglobin | A venous blood sample from the arm will be collected and glycated hemoglobin will be measured and expressed in mmol/mol and as a percentage (%). | Baseline and week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from pre- to post intervention in insulin resistance index and β-cell capacity | A venous blood sample from the arm will be collected and fasting blood glucose (mg/dL) and fasting blood insulin (micro international unit/dL) will be measured, which will determine the homeostasis model assessment (mmol/dL) and homeostasis model assessment 2 for β-cell function (%). | Baseline and week 8 | 
| Changes from pre- to pos intervention in angiogenesis | A venous blood sample from the arm will be collected and, serum Hypoxia Inducible Factor 1 alpha (HIF1-α) will be measured using specific ELISA kit instructions. | Baseline and week 8 |