Effects of Diet and Exercise on Circadian Glycemia (GLYCEMIA)

Control of Postprandial Glycemia: the Roles of Diet and Exercise

Specific aims of the study are:

1. 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
2. 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.

Study Overview

• Status: Completed
• Conditions: Glucose Intolerance
• Intervention / Treatment: Combination product: Dietary manipulation (25% carbohydrate diet) and behavioral (sedentary); Combination product: Dietary manipulation (25% carbohydrate diet) and behavioral (exercise)

Detailed Description

The two hypotheses in this study are:

1. 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
2. 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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Morning sedentary arm; 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); 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.
Active Comparator: Morning exercise arm; 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); 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
Active Comparator: Evening sedentary arm; 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); 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.
Active Comparator: Evening exercise arm; 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); 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: Northern Michigan University
• Investigators: Principal Investigator: Katarina T Borer, Ph.D., Professor Emerita

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): August 31, 2017
• Study Completion (Actual): April 1, 2019

Study Registration Dates

• First Submitted: April 17, 2019
• First Submitted That Met QC Criteria: April 17, 2019
• First Posted (Actual): April 22, 2019

Study Record Updates

• Last Update Posted (Actual): April 22, 2019
• Last Update Submitted That Met QC Criteria: April 17, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Glucose Intolerance
• Other Study ID Numbers: HUM00110793

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is no plan to share individual participant data with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No