Effects of Diet and Exercise on Circadian Glycemia

Study Overview
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Brief Summary
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Specific aims of the study are: to evaluate whether a 24-h exposure to a 25%-carbohydrate diet will reduce postprandial glycemia to the same extent in the evening (19 h) as in the morning (7 h),. and to determine whether one hour of post-meal moderate intensity exercise (at 50% of maximal effort) will further reduce postprandial glycemia. The outcome measures are: plasma concentrations of glucose, insulin, glucose-dependent-insulinotropic peptide (GIP), leptin, and the ketone body beta-hydroxybutyrate.

Detailed Description
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The two hypotheses in this study are: A 24-h exposure to a 25%-carbohydrate diet will reduce postprandial glycemia to the same extent in the evening (19 h) as in the morning (7 h), and One hour of moderate-intensity exercise (at 50% of maximal effort) will further reduce postprandial glycemia to the same extent in the evening (19 h) as in the morning (7 h). Eight postmenopausal subjects (age 58.5 years, BMI 25.6 kg/m2) participated in 4 24-h long crossover trials, two terminating at 7h and the other 2 at 19h. At each circadian time one trial required 60 minutes of moderate-intensity exercise (50% of maximal effort), and the other two involved no exercise. Three 25%-carbohydrate meals prepared by the Michigan Clinical Research Unit (MCRU) kitchen, were eaten at subjects' home, and the fourth was eaten 20 minutes after subjects' arrival at MCRU at either 19 h or 7 h. Blood was collected from antecubital catheter at 10-minute intervals until 23:20 h or 11:20 h, respectively.Plasma was treated with protease inhibitor to preserve GIP, frozen at -80o C until glucose measurements by glucose oxidase, hormone measurements by chemiluminescence, and ketone measurements by Abbott meter strips. Exercise intensity was determined before the exercise trials on a treadmill from oxygen consumption (VO2) and carbon dioxide production (VCO2) by subjects walking on a treadmill at 3 mph with the treadmill slope increased by 2% every 3 minutes. Maximal effort was established when respiratory exchange ratio (VCO2/VO2) reached or exceeded 1. The treadmill speed and slope at half maximal effort was used during the one-hour exercise bout which was initiated 40 minutes after the start of the meal.

Official Title
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Control of Postprandial Glycemia: the Roles of Diet and Exercise

Conditions
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Glucose Intolerance

Intervention / Treatment
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* Combination Product: Dietary manipulation (25% carbohydrate diet) and behavioral (exercise)
* Combination Product: Dietary manipulation (25% carbohydrate diet) and behavioral (sedentary)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: postmenopausal normal blood glucose no cholesterol medication age between 50 an 65 years overweight but not obese BMI between 25 and 30 kg/m2 weight-stable during past 6 months exercise less than 20 minutes three times a week Exclusion Criteria: metabolic disease other than hormonally-corrected hypothyroidism musculo-skeletal disability that would preclude exercise smoker do not meet inclusion criteria

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

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: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The same eight subjects participated in counterbalanced order in: (1) sedentary morning trial, (2) exercise morning trial, (3) sedentary evening trial, (4) exercise evening trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Morning sedentary arm<br>After arriving at MCRU at 7 h, and having eaten three 25%-carbohydrate meals over the previous 24 h, subjects had an antecubital-vein catheter inserted and consumed their fourth 25%-carbohydrate meal at 7:20 h. Over the next 4 hours, subjects reclined on a bed and had 3-ml blood samples collected at 10-min intervals. After the 11:20 blood sample, subjects were released from MCRU. This arm is compared to the other three arms. | Combination Product: Dietary manipulation (25% carbohydrate diet) and behavioral (sedentary)<br>* The 25% carbohydrate diet consisted of Pulmocare-vanilla liquid, white roll, butter, and string cheese in proportions to achieve 33% of weigh-maintenance diet containing 25% carbohydrate, 20% protein, and 55% fat. There was no exercise during this trial.<br>|
| Active Comparator: Morning exercise arm<br>After arriving at MCRU at 7 h, and having eaten three 25%-carbohydrate meals over the previous 24 h, subjects had an antecubital-vein catheter inserted and consumed their fourth 25%-carbohydrate meal at 7:20 h. At 8 h, subjects walked on the treadmill at 50% maximal effort. Between 7:20 and 11:20, 3-ml blood samples were collected at 10-min intervals.After the 11:20 blood sample, subjects were released from MCRU. This arm is compared to the other three arms. | Combination Product: Dietary manipulation (25% carbohydrate diet) and behavioral (exercise)<br>* The 25% carbohydrate diet consisted of Pulmocare-vanilla liquid, white roll, butter, and string cheese in proportions to achieve 33% of weigh-maintenance diet containing 25% carbohydrate, 20% protein, and 55% fat. Exercise was walking 1 hour on level treadmill at 50% of maximal effort starting 40 minutes after the beginning of the meal<br>|
| Active Comparator: Evening sedentary arm<br>After arriving at MCRU at 19 h, and having eaten three 25%-carbohydrate meals over the previous 24 h, subjects had an antecubital-vein catheter inserted and consumed their fourth 25%-carbohydrate meal at 19:20 h. Over the next 4 hours, subjects reclined on a bed and had 3-ml blood samples collected at 10-min intervals. After the 23:20 blood sample, subjects were released from MCRU. This arm is compared to the other three arms. | Combination Product: Dietary manipulation (25% carbohydrate diet) and behavioral (sedentary)<br>* The 25% carbohydrate diet consisted of Pulmocare-vanilla liquid, white roll, butter, and string cheese in proportions to achieve 33% of weigh-maintenance diet containing 25% carbohydrate, 20% protein, and 55% fat. There was no exercise during this trial.<br>|
| Active Comparator: Evening exercise arm<br>After arriving at MCRU at 19 h, and having eaten three 25%-carbohydrate meals over the previous 24 h, subjects had an antecubital-vein catheter inserted and consumed their fourth 25%-carbohydrate meal at 19:20 h. At 8 h, subjects walked on the treadmill at 50% maximal effort. Between 19:20 and 23:20, 3-ml blood samples were collected at 10-min intervals.After the 23:20 blood sample, subjects were released from MCRU. This arm is compared to the other three arms. | Combination Product: Dietary manipulation (25% carbohydrate diet) and behavioral (exercise)<br>* The 25% carbohydrate diet consisted of Pulmocare-vanilla liquid, white roll, butter, and string cheese in proportions to achieve 33% of weigh-maintenance diet containing 25% carbohydrate, 20% protein, and 55% fat. Exercise was walking 1 hour on level treadmill at 50% of maximal effort starting 40 minutes after the beginning of the meal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial glucose concentration | The area under the postprandial glucose curve | Four hours: 19:20 to 23:20 in the evening trials; 7:20 to 11:20 in the morning trials | 
| Postprandial insulin concentration | The area under the postprandial insulin curve | Four hours: 19:20 to 23:20 in the evening trials; 7:20 to 11:20 in the morning trials | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial glucose-dependent insulinotropic peptide (GIP) concentration | The area under the postprandial GIP curve | Four hours: 19:20 to 23:20 in the evening trials; 7:20 to 11:20 in the morning trials | 
| Postprandial beta-hydroxybutyrate concentration | The area under the beta-hydroxybutyrate postprandial curve | Four hours: 19:20 to 23:20 in the evening trials; 7:20 to 11:20 in the morning trials | 
| Postprandial leptin concentration | The area under the leptin postprandial curve | Four hours: 19:20 to 23:20 in the evening trials; 7:20 to 11:20 in the morning trials |