Obesity, Overweight, Overweight and Obesity, PreDiabetes, Type 2 Diabetes, Type 2 Diabetes Mellitus, Type 2 Diabetes Mellitus in Obese
Conditions
Keywords
Microbiome, Physical Activity
Brief summary
The present study is a 100-participant randomized controlled 2-arm parallel trial that employs a metagenomic approach to examine how 8 weeks of supervised moderate-intensity treadmill walking exercise (MWE) for 30-45 min 3 times/week alters the gut microbiome, serum short chain fatty acids, and the cardiometabolic profile, body weight, and body composition of individuals 30-64 years old who have overweight or obesity and have prediabetes.
Detailed description
All eligible and consented participants will complete a 3-week run-in phase during which baseline outcome assessments will be performed. During run-in weeks 1 and 2, participants will wear a Fitbit Inspire 2 smartwatch and complete three unannounced dietary recalls. During the run-in week 3 (see table below), participants will consume their 3-day standardized meal plan on days three through five, obtain a fecal sample, complete a study questionnaire, and complete a study assessment visit. To quantify compliance with the 3-day meal plan, participants will be provided with a paper checklist of all foods to be consumed, and will be asked to indicate which foods were consumed and to document any deviation. The study assessment visit will include a fasting blood draw (at baseline and week eight only), blood pressure in triplicate, weight measure and body fat assessment in duplicate, and a saliva sample.
Interventions
BEHAVIORALPhysical Activity Intervention
Three walking sessions/week for a total of 8 weeks (24 total sessions) - Walking sessions will either take place on new commercial treadmills in the Epidemiology Clinical Research Center or remotely at or around a participant's home. Regardless of the walking location, walking sessions will be 30 min in duration during intervention weeks 1 through 4 and a minimum of 45 min each during intervention weeks 5 through 8.
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Classified as overweight or obese with BMI 25.0-39.9 kg/m2. * Documentation\* of a prediabetes diagnosis within one year of enrollment by physician or primary care provider based on lab tests showing a fasted blood glucose of 100-125 mg/dL, a 2-hour oral glucose tolerance test of 140-199 mg/dL, or an HbA1c level of 5.7%-6.4%76; OR a study screening lab value of HbA1C within the afore mentioned range. * Currently engaged in \<100 min/week of physical activity - confirmed by questionnaire. * No exercise contraindications as assessed by the Physical Activity Readiness Questionnaire (PAR-Q)78-this Questionnaire involves seven yes or no questions regarding an individual's health status, with answering yes to any one of these questions requiring a prospective participant to acquire a written doctor's note stating they can safely participate in the trial's exercise intervention. * No self-reported physical/mental disabilities or gastrointestinal conditions. * No antibiotic usage within the last 45 days. * Stable weight over the last 6 months (\<10% change). * Not currently pregnant, planning to become pregnant, or currently breastfeeding. * Willing to maintain current dietary and exercise habits, aside from any changes to be made per the study exercise protocol. * Note: Documentation can include either a print out or screen shot of the lab value illustrating eligibility, along with the date of the test and the participant's name. If a hard copy is provided, the date and name will be redacted.
Exclusion criteria
* Self-reported use of metformin and/or other medications that could interfere with the primary outcome. * History of bariatric surgery or a history of other medical interventions that would interfere with the primary outcome.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Shannon Index (Unitless) | 8 weeks | Changes to the gut microbiome will be assessed via metagenomic sequencing, from pre- to post-intervention. The Shannon Index-a measure of microbial community diversity-will be the primary indicator for changes in gut microbiota composition, and will be assessed at baseline, and following the 4th and 8th weeks. Index values are unitless and range from 0 to 1. Lower values indicate more diversity while higher values indicate less diversity. Outcome will be reported at baseline, 4 weeks, and 8 weeks and as the change from baseline to 4 weeks and baseline to 8 weeks. |
| Change in Serum Short Chain Fatty Acids (SCFA) | 8 weeks | Participants will undergo fasted blood draws to assess serum SCFA levels. This work will be performed using the Metabolon pipeline. Outcome is reported as the sum of the serum concentrations of acetate, propionate, and butyrate in Z-score units. We report the Week 8 means and standard errors from a linear model adjusted for the Week 0 (baseline) values. The original units are reported in ng/mL and the final results are reported as standardized z-scores in which each value subtracts the mean and the difference is divided by the standard deviation. Higher values represent higher levels of SCFA which is considered better. The scale is in standard deviation units. A value of 0 = the population mean. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Insulin | 8 weeks | Fasting insulin will be measured by laboratory test and reported in units of pm/ml. We report the Week 8 means and standard errors from a linear model adjusted for the Week 0 (baseline) values. |
| Fasting Glucose | 8 weeks | Fasting glucose will be measured by standard laboratory test and reported in units of mg/dl. We report the Week 8 means and standard errors from a linear model adjusted for the Week 0 (baseline) values. |
| C-reactive Protein (CRP) | 8 weeks | C-reactive protein (CRP) will be measured by laboratory test and reported in units of mg/l. We report the Week 8 means and standard errors from a linear model adjusted for the Week 0 (baseline) values. |
| High-density Lipoprotein Cholesterol (HDL-C) | 8 weeks | High-density lipoprotein cholesterol (HDL-C) will be measured using standard laboratory test and report in units of mg/dl. We report the Week 8 means and standard errors from a linear model adjusted for the Week 0 (baseline) values. |
| Body Composition | 8 weeks | Body composition will be analyzed using bioelectrical impedance. Outcome will be reported as percent body fat. We report the Week 8 means and standard errors from a linear model adjusted for the Week 0 (baseline) values. |
| Cardiometabolic Risk Score (CMR) | 8 weeks | The Cardiometabolic Risk Score (CMR) is the mean Z-score across systolic blood pressure, glucose, insulin, HDL, % body fat, and triglycerides. We report the Week 8 means and standard errors from a linear model adjusted for the Week 0 (baseline) values. The final results are reported as standardized z-scores in which each value subtracts the mean and the difference is divided by the standard deviation. Higher values represent higher levels of cardiometabolic risk which is considered worse. The scale is in standard deviation units. A value of 0 = the population mean. |
| Resting Systolic Blood Pressure (BP) | 8 weeks | Resting systolic blood pressure will be reported in units of mmHg. We report the Week 8 means and standard errors from a linear model adjusted for the Week 0 (baseline) values. |
| Triglycerides | 8 weeks | Blood triglycerides will be measured using a standard laboratory test and reported in units of mg/dl. We report the Week 8 means and standard errors from a linear model adjusted for the Week 0 (baseline) values. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited on a rolling basis through a combination of the following methods: clinical referrals via partners within community-based health clinics, and fliers posted on physical (e.g. campus buildings, community billboards) and virtual (e.g. Facebook, NextDoor) walls. Finally, eligible participants based on electronic health record were identified and and invitation was sent via 'My Chart' directly to the prospective participant.
Pre-assignment details
After consenting, participants entered a three week run-in period during which time they provided a baseline stool sample, continued regular activity, used a study provided fitbit to monitor baseline physical activity levels, and responded to three phone dietary assessments.
Participants by arm
| Arm | Count |
|---|---|
| Intervention Three walking sessions/week for a total of 8 weeks (24 total sessions) - Walking sessions occurred remotely at or around a participant's home. Regardless of the walking location, walking sessions were 30 min in duration during intervention weeks 1 through 4 and a minimum of 45 min each during intervention weeks 5 through 8. | 39 |
| Control Participants in this group were asked to maintain their normal level of physical activity. | 38 |
| Total | 77 |
Baseline characteristics
| Characteristic | Intervention | Total | Control |
|---|---|---|---|
| Age, Continuous | 49.9 Years STANDARD_DEVIATION 9.3 | 51.4 Years STANDARD_DEVIATION 9 | 53.1 Years STANDARD_DEVIATION 8.5 |
| BMI | 34.7 kg/m^2 STANDARD_DEVIATION 6.1 | 34.4 kg/m^2 STANDARD_DEVIATION 5.7 | 34.1 kg/m^2 STANDARD_DEVIATION 5.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 6 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 64 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 7 Participants | 4 Participants |
| Percent body fat | 44.0 % STANDARD_DEVIATION 7.2 | 43.8 % STANDARD_DEVIATION 6.9 | 43.5 % STANDARD_DEVIATION 6.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 10 Participants | 6 Participants |
| Race (NIH/OMB) White | 31 Participants | 58 Participants | 27 Participants |
| Region of Enrollment United States | 39 Participants | 77 Participants | 38 Participants |
| Sex: Female, Male Female | 34 Participants | 66 Participants | 32 Participants |
| Sex: Female, Male Male | 5 Participants | 11 Participants | 6 Participants |
| Weight (kg) | 99 Kilogram STANDARD_DEVIATION 21.5 | 98.1 Kilogram STANDARD_DEVIATION 20.5 | 97.1 Kilogram STANDARD_DEVIATION 19.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 38 |
| other Total, other adverse events | 0 / 39 | 0 / 38 |
| serious Total, serious adverse events | 0 / 39 | 0 / 38 |
Outcome results
Primary
Change in Serum Short Chain Fatty Acids (SCFA)
Participants will undergo fasted blood draws to assess serum SCFA levels. This work will be performed using the Metabolon pipeline. Outcome is reported as the sum of the serum concentrations of acetate, propionate, and butyrate in Z-score units. We report the Week 8 means and standard errors from a linear model adjusted for the Week 0 (baseline) values. The original units are reported in ng/mL and the final results are reported as standardized z-scores in which each value subtracts the mean and the difference is divided by the standard deviation. Higher values represent higher levels of SCFA which is considered better. The scale is in standard deviation units. A value of 0 = the population mean.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Serum Short Chain Fatty Acids (SCFA) | 0.19 score on a scale | Standard Error 0.107 |
| Control | Change in Serum Short Chain Fatty Acids (SCFA) | 0.08 score on a scale | Standard Error 0.101 |
Primary
Change in Shannon Index (Unitless)
Changes to the gut microbiome will be assessed via metagenomic sequencing, from pre- to post-intervention. The Shannon Index-a measure of microbial community diversity-will be the primary indicator for changes in gut microbiota composition, and will be assessed at baseline, and following the 4th and 8th weeks. Index values are unitless and range from 0 to 1. Lower values indicate more diversity while higher values indicate less diversity. Outcome will be reported at baseline, 4 weeks, and 8 weeks and as the change from baseline to 4 weeks and baseline to 8 weeks.
Time frame: 8 weeks
Population: There were 6 participants with missing microbiome data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Shannon Index (Unitless) | -0.20 units on a scale | Standard Error 0.073 |
| Control | Change in Shannon Index (Unitless) | 0.013 units on a scale | Standard Error 0.072 |
Secondary
Body Composition
Body composition will be analyzed using bioelectrical impedance. Outcome will be reported as percent body fat. We report the Week 8 means and standard errors from a linear model adjusted for the Week 0 (baseline) values.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Body Composition | 43.5 Percentage | Standard Error 0.41 |
| Control | Body Composition | 43.6 Percentage | Standard Error 0.4 |
Secondary
Cardiometabolic Risk Score (CMR)
The Cardiometabolic Risk Score (CMR) is the mean Z-score across systolic blood pressure, glucose, insulin, HDL, % body fat, and triglycerides. We report the Week 8 means and standard errors from a linear model adjusted for the Week 0 (baseline) values. The final results are reported as standardized z-scores in which each value subtracts the mean and the difference is divided by the standard deviation. Higher values represent higher levels of cardiometabolic risk which is considered worse. The scale is in standard deviation units. A value of 0 = the population mean.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Cardiometabolic Risk Score (CMR) | -.01 z-score standardized units | Standard Error 0.05 |
| Control | Cardiometabolic Risk Score (CMR) | -.04 z-score standardized units | Standard Error 0.047 |
Secondary
C-reactive Protein (CRP)
C-reactive protein (CRP) will be measured by laboratory test and reported in units of mg/l. We report the Week 8 means and standard errors from a linear model adjusted for the Week 0 (baseline) values.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | C-reactive Protein (CRP) | 4.6 mg/L | Standard Error 0.36 |
| Control | C-reactive Protein (CRP) | 4.5 mg/L | Standard Error 0.33 |
Secondary
Fasting Glucose
Fasting glucose will be measured by standard laboratory test and reported in units of mg/dl. We report the Week 8 means and standard errors from a linear model adjusted for the Week 0 (baseline) values.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Fasting Glucose | 105.0 mg/dL | Standard Error 1.42 |
| Control | Fasting Glucose | 105.0 mg/dL | Standard Error 1.35 |
Secondary
Fasting Insulin
Fasting insulin will be measured by laboratory test and reported in units of pm/ml. We report the Week 8 means and standard errors from a linear model adjusted for the Week 0 (baseline) values.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Fasting Insulin | 132.5 pm/L | Standard Error 8.96 |
| Control | Fasting Insulin | 134.8 pm/L | Standard Error 8.44 |
Secondary
High-density Lipoprotein Cholesterol (HDL-C)
High-density lipoprotein cholesterol (HDL-C) will be measured using standard laboratory test and report in units of mg/dl. We report the Week 8 means and standard errors from a linear model adjusted for the Week 0 (baseline) values.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | High-density Lipoprotein Cholesterol (HDL-C) | 53.4 mg/dL | Standard Error 0.73 |
| Control | High-density Lipoprotein Cholesterol (HDL-C) | 51.7 mg/dL | Standard Error 0.69 |
Secondary
Resting Systolic Blood Pressure (BP)
Resting systolic blood pressure will be reported in units of mmHg. We report the Week 8 means and standard errors from a linear model adjusted for the Week 0 (baseline) values.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Resting Systolic Blood Pressure (BP) | 121 mmHg | Standard Error 1.9 |
| Control | Resting Systolic Blood Pressure (BP) | 120 mmHg | Standard Error 1.8 |
Secondary
Triglycerides
Blood triglycerides will be measured using a standard laboratory test and reported in units of mg/dl. We report the Week 8 means and standard errors from a linear model adjusted for the Week 0 (baseline) values.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Triglycerides | 147.2 mg/dL | Standard Error 7.08 |
| Control | Triglycerides | 142.7 mg/dL | Standard Error 6.7 |