Glucotoxicity and Acute Exercise

Study Overview
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Brief Summary
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Experimental hyperglycemia (5 hours) will be induced via a constant- or fluctuating-rate glucose infusion to establish different patterns of glycemia in healthy individuals. The effects of these acute models of hyperglycemia on the adaptations to a single aerobic exercise bout will be tested. Changes in pancreatic endocrine function, insulin sensitivity, endothelial function, and oxidative stress will be measured.

Official Title
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The Effects of Hyperglycaemia on the Response to Acute Exercise

Conditions
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Type 1 Diabetes, Type 2 Diabetes

Intervention / Treatment
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* Behavioral: Exercise
* Procedure: Hyperglycemia


Participation Criteria
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Eligibility Criteria
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Inclusion criteria for participation: Male Age 18-50 years Body Mass Index 19-30 kg/m2 Generally healthy Exclusion criteria for participation: Regular use of anti-inflammatory medication Smokers More than 2 kg weight change in prior 6 months Previous weight loss surgery Cancer, or evidence of chronic haematological, pulmonary, cardiac, hepatic, renal, or gastrointestinal disease Evidence of diabetes Engaged in moderate or vigorous activity on more than 5 days per week

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normoglycemia + exercise<br>At T = 0 h participants will undergo an intravenous glucose tolerance test (IVGTT, 0.33 g/kg glucose) immediately followed by a 4-hour rest period. At T = 5 h, participants will undertake 45 minutes of moderate-intensity (70% VO2max) bicycle ergometry. Immediately following (T = 6 h) and 1- (T = 7 h), 3- (T = 9 h), and 18- hours (T = 24 h) after exercise, participants will undergo additional IVGTTs. | Behavioral: Exercise<br> <br> |
| Experimental: Steady-State Hyperglycemia + exercise<br>At T = 0 h participants will undergo an intravenous glucose tolerance test (IVGTT, 0.33 g/kg glucose) immediately followed by a 4-hour rest period. During this time, steady-state hyperglycemia ( 10 mM) will be induced experimentally via a variable-rate intravenous infusion of 20% dextrose. At T = 5 h, participants will undertake 45 minutes of moderate-intensity (70% VO2max) bicycle ergometry. Immediately following (T = 6 h) and 1- (T = 7 h), 3- (T = 9 h), and 18- hours (T = 24 h) after exercise, participants will undergo additional IVGTTs. | Behavioral: Exercise<br> <br> Procedure: Hyperglycemia<br> <br> |
| Experimental: Fluctuating Hyperglycemia + exercise<br>At T = 0 h participants will undergo an intravenous glucose tolerance test (IVGTT, 0.33 g/kg glucose) immediately followed by a 4-hour rest period. During this time, fluctuating hyperglycemia ( 8-15 mM) will be induced by intravenously injecting 0.15 g/kg boluses of 20% dextrose every 30 minutes. At T = 5 h, participants will undertake 45 minutes of moderate-intensity (70% VO2max) bicycle ergometry. Immediately following (T = 6 h) and 1- (T = 7 h), 3- (T = 9 h), and 18- hours (T = 24 h) after exercise, participants will undergo additional IVGTTs. | Behavioral: Exercise<br> <br> Procedure: Hyperglycemia<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pancreatic endocrine function | The plasma insulin, C-peptide, and glucagon responses to a 0.33 g/kg intravenous glucose tolerance test (IVGTT) will be measured. In each trial, the IVGTT will be performed at T = 0, 6, 7, 9, and 24 hours. | 0, 6, 7, 9, and 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose tolerance | Glucose tolerance will be measured during an IVGTT in each trial at T = 0, 6, 7, 9, and 24 hours. | 0, 6, 7, 9, and 24 hours | 
| Endothelial function | Blood flow and flow-mediated dilation by Doppler ultrasound will be measured in each trial at T = 0, 6, 7, 9, and 24 hours. | 0, 6, 7, 9, and 24 hours | 
| Oxidative stress | Urine will be collected over the whole 24-hour period of each trial and 8-iso Prostaglandin F3α will be measured. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucotoxicity, Exercise, Beta-cell function