Physical Activity
Conditions
Brief summary
The investigators propose that post-exercise milk protein feeding will enhance the mitochondrial protein synthesis (biogenesis) response to an exercise-training program. In addition, the investigators propose that this stimulatory effect of protein feeding will overcome the potential blunting effect of metformin on exercise responses. The investigators will investigate these outcomes over a 12-week exercise-training program in older adults with pre-diabetes with or without metformin treatment.
Detailed description
This is a randomized, placebo controlled, double blind study. 60 men and women over the age of 55 with indications of pre-diabetes will be recruited for participation and randomly assigned to one of four 12 week exercise training programs: 1)Supervised aerobic exercise 3 days per week followed by a carbohydrate drink along with daily oral administration of Metformin. 2) Supervised aerobic exercise 3 days per week followed by a protein drink along with daily oral administration of Metformin. 3) Supervised aerobic exercise 3 days per week followed by a carbohydrate drink along with daily oral administration of matching placebo. 4) Supervised aerobic exercise 3 days per week followed by a protein drink along with daily oral administration of placebo. Daily administration of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week 4 during a 12 week exercise training program. The titration dosing scheme and taking metformin/placebo with meals will help reduce the most common side effects (i.e.,gastrointestinal discomfort). If participants experience gastrointestinal discomfort, the dose will be lowered to 1500 mg/day.
Interventions
DRUGMetformin
Daily administration of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week 4 during a 12 week exercise training program.
DRUGPlacebo
Daily administration of matching placebo during a 12 week exercise training program.
DIETARY_SUPPLEMENTCarbohydrate Beverage
Supervised aerobic exercise 3 days per week followed by a carbohydrate drink
DIETARY_SUPPLEMENTProtein Beverage
Supervised aerobic exercise 3 days per week followed by a protein drink
Sponsors
Colorado State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Participants were assigned to either Metformin-Protein, Metformin-Carbohydrate, Placebo-Protein, and Placebo-Carbohydrate.
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* 55 years or older * Individuals with Prediabetes defined as impaired fasting glucose (100 to 126 mg/dl), HbA1c (5.7-6.4%), and/or impaired glucose tolerance defined as 2 hour postprandial blood glucose of 140 to 200 mg/dl.
Exclusion criteria
* Medications contraindicated with Metformin (Dofetilide, Lamotrigine, Pegvisomant, Somatropin, Trimethoprim, Trospium, Gatifloxacin, Cephalexin, Cimetidine, Dalfampridine) * Recent (less than 6 weeks) or planned imaging that requires IV contrast, * Renal dysfunction creatinine ≥ 1.3 mg/dL in men or ≥ 1.2 mg/dL in women * Alanine Aminotransferase (ALT) levels exceed 52 IU/L * Heart, Kidney or Liver Disease * Type I or Type II Diabetes * Anti-coagulant therapy (warfarin/heparin) * Lung/respiratory dysfunction * Medications affecting primary outcomes * Lactose Intolerant * Tobacco Use * Heavy Alcohol Use * Cancer * Lidocaine Allergy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glucose Tolerance | Baseline and 12 weeks | Oral glucose tolerance test was used to measure glucose tolerance. These data are reported as the mean at baseline (pre) and the mean at 12 weeks (post). |
| Peak Aerobic Capacity | Baseline and 12 weeks | Indirect calorimetry was used to measure peak oxygen consumption during a maximal, graded exercise test. These data are reported as the percent change from baseline compared to 12 weeks. |
| DNA Synthesis | Baseline and 12 weeks | Incorporation of Deuterium Oxide into DNA will be measured before and after the 12 week interventions. |
| Mitochondrial Function | Baseline and 12 weeks | Oxygen consumption was assessed via high-resolution mitochondrial respirometry in permeabilized skeletal muscle. This outcome was assessed via 2 different protocols; Protocol 1 was a substrate-uncoupler-inhibitor titration (SUIT) and Protocol 2 was an adenosine diphosphate (ADP) titration. These data are reported as the percent change from baseline compared to 12 weeks. |
| Protein Synthesis | 12 weeks | Incorporation of deuterium into proteins to calculate cumulative synthesis rates. Protein synthesis was measured in sub cellular fractions of skeletal muscle including mixed, cytoplasmic and mitochondrial enriched fractions. These data are reported as the mean at 12 weeks. |
| Body Composition | Baseline and 12 weeks | Dual energy x-ray absorptiometry was used to assess fat-free and fat mass. These data are reported as the mean at baseline (pre) and mean at 12 weeks (post). |
| Insulin Sensitivity | Baseline and 12 weeks | Oral glucose tolerance test was used to measure whole-body insulin sensitivity. These data are reported as the mean at baseline (pre) and the mean at 12 weeks (post). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intracellular Signaling Proteins | Baseline and 12 weeks | Protein content of intracellular signaling proteins that are implicated in mitochondrial biogenesis, mitochondrial function and insulin sensitivity were measured by Western blotting. Densitometry results are reported as a ratio of protein divided by total amount of protein expressed. All proteins of interest are expressed as phosphorylated relative to total. These data are reported as the percent change from baseline compared to 12 weeks. |
| Glucose Profiles From Real-Time Continuous Glucose Monitoring | Baseline, Weeks 6-8, 12 weeks | Data derived from Continuous Glucose Monitoring was used to calculate mean glucose and mean average glucose excursions (MAGE). These data are reported as the percent change at baseline (pre), 6-8 weeks (Mid), and 12 weeks (post) . |
Countries
United States
Participant flow
Pre-assignment details
Participants were assigned to either Metformin-Protein, Metformin-Carbohydrate, Placebo-Protein, and Placebo-Carbohydrate.
Participants by arm
| Arm | Count |
|---|---|
| Metformin: Carbohydrate Daily oral administration of Metformin with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training. Immediately after each exercise session, participants consumed a standardized beverage that consisted of carbohydrates (82g) plus protein (2g).
Metformin: Daily administration of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week 4 during a 12 week exercise training program. | 14 |
| Placebo: Carbohydrate Daily oral administration of matching placebo with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training The dose of matching placebo will begin as one tablet for the first week and will increase by one tablet/day/week until reaching 4 tablets by week 4.
Immediately after each exercise session, participants consumed a standardized beverage that consisted of carbohydrates (82g) plus protein (2g). | 12 |
| Metformin: Protein Daily oral administration of Metformin with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training. Immediately after each exercise session, participants consumed a standardized beverage that consisted of carbohydrate (63g) plus protein (20g).
Metformin: Daily administration of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week 4 during a 12 week exercise training program. | 13 |
| Placebo: Protein Daily oral administration of matching placebo with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training The dose of matching placebo will begin as one tablet for the first week and will increase by one tablet/day/week until reaching 4 tablets by week 4.
Immediately after each exercise session, participants consumed a standardized beverage that consisted of carbohydrates (63 g) plus protein (20g). | 14 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Metformin: Carbohydrate | Placebo: Carbohydrate | Metformin: Protein | Placebo: Protein | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 12 Participants | 13 Participants | 14 Participants | 53 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 14 Participants | 12 Participants | 13 Participants | 14 Participants | 53 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 14 participants | 12 participants | 13 participants | 14 participants | 53 participants |
| Sex: Female, Male Female | 11 Participants | 10 Participants | 10 Participants | 11 Participants | 42 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 13 | 0 / 14 | 0 / 15 |
| other Total, other adverse events | 5 / 14 | 5 / 13 | 9 / 14 | 8 / 15 |
| serious Total, serious adverse events | 0 / 14 | 0 / 13 | 0 / 14 | 0 / 15 |
Outcome results
Primary
Body Composition
Dual energy x-ray absorptiometry was used to assess fat-free and fat mass. These data are reported as the mean at baseline (pre) and mean at 12 weeks (post).
Time frame: Baseline and 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metformin: Carbohydrate | Body Composition | Pre Fat Free Mass | 48 Kilograms | Standard Deviation 3 |
| Metformin: Carbohydrate | Body Composition | Post Fat Free Mass | 47 Kilograms | Standard Deviation 2 |
| Metformin: Carbohydrate | Body Composition | Pre Fat Mass | 34 Kilograms | Standard Deviation 3 |
| Metformin: Carbohydrate | Body Composition | Post Fat Mass | 32 Kilograms | Standard Deviation 3 |
| Placebo:Carbohydrate | Body Composition | Post Fat Free Mass | 48 Kilograms | Standard Deviation 2 |
| Placebo:Carbohydrate | Body Composition | Post Fat Mass | 34 Kilograms | Standard Deviation 2 |
| Placebo:Carbohydrate | Body Composition | Pre Fat Free Mass | 48 Kilograms | Standard Deviation 3 |
| Placebo:Carbohydrate | Body Composition | Pre Fat Mass | 35 Kilograms | Standard Deviation 3 |
| Metformin: Protein | Body Composition | Pre Fat Mass | 33 Kilograms | Standard Deviation 3 |
| Metformin: Protein | Body Composition | Post Fat Mass | 31 Kilograms | Standard Deviation 3 |
| Metformin: Protein | Body Composition | Pre Fat Free Mass | 50 Kilograms | Standard Deviation 2 |
| Metformin: Protein | Body Composition | Post Fat Free Mass | 50 Kilograms | Standard Deviation 3 |
| Placebo: Protein | Body Composition | Post Fat Mass | 32 Kilograms | Standard Deviation 4 |
| Placebo: Protein | Body Composition | Pre Fat Free Mass | 46 Kilograms | Standard Deviation 2 |
| Placebo: Protein | Body Composition | Post Fat Free Mass | 46 Kilograms | Standard Deviation 2 |
| Placebo: Protein | Body Composition | Pre Fat Mass | 33 Kilograms | Standard Deviation 4 |
Primary
DNA Synthesis
Incorporation of Deuterium Oxide into DNA will be measured before and after the 12 week interventions.
Time frame: Baseline and 12 weeks
Population: No data was collected.
Primary
Glucose Tolerance
Oral glucose tolerance test was used to measure glucose tolerance. These data are reported as the mean at baseline (pre) and the mean at 12 weeks (post).
Time frame: Baseline and 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metformin: Carbohydrate | Glucose Tolerance | Pre 2 hour Glucose | 131 mg/dL | Standard Deviation 7 |
| Metformin: Carbohydrate | Glucose Tolerance | Post 2 hour Glucose | 133 mg/dL | Standard Deviation 7 |
| Placebo:Carbohydrate | Glucose Tolerance | Post 2 hour Glucose | 115 mg/dL | Standard Deviation 7 |
| Placebo:Carbohydrate | Glucose Tolerance | Pre 2 hour Glucose | 116 mg/dL | Standard Deviation 7 |
| Metformin: Protein | Glucose Tolerance | Pre 2 hour Glucose | 108 mg/dL | Standard Deviation 14 |
| Metformin: Protein | Glucose Tolerance | Post 2 hour Glucose | 112 mg/dL | Standard Deviation 12 |
| Placebo: Protein | Glucose Tolerance | Pre 2 hour Glucose | 102 mg/dL | Standard Deviation 7 |
| Placebo: Protein | Glucose Tolerance | Post 2 hour Glucose | 107 mg/dL | Standard Deviation 10 |
Primary
Insulin Sensitivity
Oral glucose tolerance test was used to measure whole-body insulin sensitivity. These data are reported as the mean at baseline (pre) and the mean at 12 weeks (post).
Time frame: Baseline and 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metformin: Carbohydrate | Insulin Sensitivity | Pre 2 hour Insulin | 86 microInternational units/mL | Standard Deviation 20 |
| Metformin: Carbohydrate | Insulin Sensitivity | Post 2 hour Insulin | 91 microInternational units/mL | Standard Deviation 34 |
| Placebo:Carbohydrate | Insulin Sensitivity | Post 2 hour Insulin | 51 microInternational units/mL | Standard Deviation 8 |
| Placebo:Carbohydrate | Insulin Sensitivity | Pre 2 hour Insulin | 57 microInternational units/mL | Standard Deviation 14 |
| Metformin: Protein | Insulin Sensitivity | Pre 2 hour Insulin | 39 microInternational units/mL | Standard Deviation 7 |
| Metformin: Protein | Insulin Sensitivity | Post 2 hour Insulin | 32 microInternational units/mL | Standard Deviation 7 |
| Placebo: Protein | Insulin Sensitivity | Pre 2 hour Insulin | 56 microInternational units/mL | Standard Deviation 13 |
| Placebo: Protein | Insulin Sensitivity | Post 2 hour Insulin | 55 microInternational units/mL | Standard Deviation 15 |
Primary
Mitochondrial Function
Oxygen consumption was assessed via high-resolution mitochondrial respirometry in permeabilized skeletal muscle. This outcome was assessed via 2 different protocols; Protocol 1 was a substrate-uncoupler-inhibitor titration (SUIT) and Protocol 2 was an adenosine diphosphate (ADP) titration. These data are reported as the percent change from baseline compared to 12 weeks.
Time frame: Baseline and 12 weeks
Population: The number analyzed differs from the overall number due to subject withdrawal from study and/or limited muscle sample.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metformin: Carbohydrate | Mitochondrial Function | SUIT | 7.1 percent change in pmol/s/mg tissue | Standard Error 12.8 |
| Metformin: Carbohydrate | Mitochondrial Function | ADP titration | 3.4 percent change in pmol/s/mg tissue | Standard Error 8.2 |
| Placebo:Carbohydrate | Mitochondrial Function | ADP titration | 42.3 percent change in pmol/s/mg tissue | Standard Error 12.9 |
| Placebo:Carbohydrate | Mitochondrial Function | SUIT | 43.2 percent change in pmol/s/mg tissue | Standard Error 15.5 |
| Metformin: Protein | Mitochondrial Function | SUIT | 15.6 percent change in pmol/s/mg tissue | Standard Error 7.6 |
| Metformin: Protein | Mitochondrial Function | ADP titration | 4.7 percent change in pmol/s/mg tissue | Standard Error 11.7 |
| Placebo: Protein | Mitochondrial Function | SUIT | 13.8 percent change in pmol/s/mg tissue | Standard Error 6.9 |
| Placebo: Protein | Mitochondrial Function | ADP titration | 16 percent change in pmol/s/mg tissue | Standard Error 9.4 |
Primary
Peak Aerobic Capacity
Indirect calorimetry was used to measure peak oxygen consumption during a maximal, graded exercise test. These data are reported as the percent change from baseline compared to 12 weeks.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin: Carbohydrate | Peak Aerobic Capacity | 3 percent change of Liters/Minute | Standard Error 2.1 |
| Placebo:Carbohydrate | Peak Aerobic Capacity | 4.7 percent change of Liters/Minute | Standard Error 3.8 |
| Metformin: Protein | Peak Aerobic Capacity | 4.9 percent change of Liters/Minute | Standard Error 2.8 |
| Placebo: Protein | Peak Aerobic Capacity | 8.5 percent change of Liters/Minute | Standard Error 2.9 |
Primary
Protein Synthesis
Incorporation of deuterium into proteins to calculate cumulative synthesis rates. Protein synthesis was measured in sub cellular fractions of skeletal muscle including mixed, cytoplasmic and mitochondrial enriched fractions. These data are reported as the mean at 12 weeks.
Time frame: 12 weeks
Population: The number analyzed differs from the over all number due to subject withdrawal from study and/or limited muscle sample.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metformin: Carbohydrate | Protein Synthesis | Mitochondrial | 1.09 % of protein synthesis rate per day | Standard Error 0.09 |
| Metformin: Carbohydrate | Protein Synthesis | Mixed | 1.24 % of protein synthesis rate per day | Standard Error 0.06 |
| Metformin: Carbohydrate | Protein Synthesis | Cytoplasmic | 1.15 % of protein synthesis rate per day | Standard Error 0.07 |
| Placebo:Carbohydrate | Protein Synthesis | Cytoplasmic | 1.00 % of protein synthesis rate per day | Standard Error 0.05 |
| Placebo:Carbohydrate | Protein Synthesis | Mixed | 1.15 % of protein synthesis rate per day | Standard Error 0.04 |
| Placebo:Carbohydrate | Protein Synthesis | Mitochondrial | 0.97 % of protein synthesis rate per day | Standard Error 0.08 |
| Metformin: Protein | Protein Synthesis | Mitochondrial | 1.03 % of protein synthesis rate per day | Standard Error 0.04 |
| Metformin: Protein | Protein Synthesis | Mixed | 1.1 % of protein synthesis rate per day | Standard Error 0.04 |
| Metformin: Protein | Protein Synthesis | Cytoplasmic | 1.05 % of protein synthesis rate per day | Standard Error 0.03 |
| Placebo: Protein | Protein Synthesis | Cytoplasmic | 1.06 % of protein synthesis rate per day | Standard Error 0.05 |
| Placebo: Protein | Protein Synthesis | Mixed | 1.14 % of protein synthesis rate per day | Standard Error 0.04 |
| Placebo: Protein | Protein Synthesis | Mitochondrial | 0.95 % of protein synthesis rate per day | Standard Error 0.07 |
Secondary
Glucose Profiles From Real-Time Continuous Glucose Monitoring
Data derived from Continuous Glucose Monitoring was used to calculate mean glucose and mean average glucose excursions (MAGE). These data are reported as the percent change at baseline (pre), 6-8 weeks (Mid), and 12 weeks (post) .
Time frame: Baseline, Weeks 6-8, 12 weeks
Population: Only a subset of subjects were studied.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metformin: Carbohydrate | Glucose Profiles From Real-Time Continuous Glucose Monitoring | Mean Glucose- Pre | 116 percent change of milligrams/deciliter | Standard Error 9.9 |
| Metformin: Carbohydrate | Glucose Profiles From Real-Time Continuous Glucose Monitoring | Mean Glucose- Mid | 105.3 percent change of milligrams/deciliter | Standard Error 6.2 |
| Metformin: Carbohydrate | Glucose Profiles From Real-Time Continuous Glucose Monitoring | Mean Glucose-Post | 110.7 percent change of milligrams/deciliter | Standard Error 2.7 |
| Metformin: Carbohydrate | Glucose Profiles From Real-Time Continuous Glucose Monitoring | MAGE- Pre | 61.3 percent change of milligrams/deciliter | Standard Error 15 |
| Metformin: Carbohydrate | Glucose Profiles From Real-Time Continuous Glucose Monitoring | MAGE- Mid | 53.6 percent change of milligrams/deciliter | Standard Error 6.9 |
| Metformin: Carbohydrate | Glucose Profiles From Real-Time Continuous Glucose Monitoring | MAGE- Post | 56.4 percent change of milligrams/deciliter | Standard Error 8.4 |
| Placebo:Carbohydrate | Glucose Profiles From Real-Time Continuous Glucose Monitoring | MAGE- Post | 58.6 percent change of milligrams/deciliter | Standard Error 7.1 |
| Placebo:Carbohydrate | Glucose Profiles From Real-Time Continuous Glucose Monitoring | MAGE- Pre | 49.5 percent change of milligrams/deciliter | Standard Error 4.2 |
| Placebo:Carbohydrate | Glucose Profiles From Real-Time Continuous Glucose Monitoring | Mean Glucose- Pre | 116.7 percent change of milligrams/deciliter | Standard Error 5.9 |
| Placebo:Carbohydrate | Glucose Profiles From Real-Time Continuous Glucose Monitoring | Mean Glucose-Post | 116.1 percent change of milligrams/deciliter | Standard Error 6.2 |
| Placebo:Carbohydrate | Glucose Profiles From Real-Time Continuous Glucose Monitoring | Mean Glucose- Mid | 104.7 percent change of milligrams/deciliter | Standard Error 4.1 |
| Placebo:Carbohydrate | Glucose Profiles From Real-Time Continuous Glucose Monitoring | MAGE- Mid | 40.8 percent change of milligrams/deciliter | Standard Error 3.1 |
| Metformin: Protein | Glucose Profiles From Real-Time Continuous Glucose Monitoring | Mean Glucose- Mid | 93.7 percent change of milligrams/deciliter | Standard Error 7.7 |
| Metformin: Protein | Glucose Profiles From Real-Time Continuous Glucose Monitoring | Mean Glucose-Post | 107.8 percent change of milligrams/deciliter | Standard Error 3.7 |
| Metformin: Protein | Glucose Profiles From Real-Time Continuous Glucose Monitoring | MAGE- Pre | 41.1 percent change of milligrams/deciliter | Standard Error 3 |
| Metformin: Protein | Glucose Profiles From Real-Time Continuous Glucose Monitoring | MAGE- Post | 42.1 percent change of milligrams/deciliter | Standard Error 2.9 |
| Metformin: Protein | Glucose Profiles From Real-Time Continuous Glucose Monitoring | MAGE- Mid | 36.2 percent change of milligrams/deciliter | Standard Error 2.5 |
| Metformin: Protein | Glucose Profiles From Real-Time Continuous Glucose Monitoring | Mean Glucose- Pre | 113.3 percent change of milligrams/deciliter | Standard Error 3.5 |
| Placebo: Protein | Glucose Profiles From Real-Time Continuous Glucose Monitoring | MAGE- Mid | 37.1 percent change of milligrams/deciliter | Standard Error 4.9 |
| Placebo: Protein | Glucose Profiles From Real-Time Continuous Glucose Monitoring | MAGE- Post | 46.3 percent change of milligrams/deciliter | Standard Error 5.5 |
| Placebo: Protein | Glucose Profiles From Real-Time Continuous Glucose Monitoring | Mean Glucose- Mid | 95.2 percent change of milligrams/deciliter | Standard Error 10.7 |
| Placebo: Protein | Glucose Profiles From Real-Time Continuous Glucose Monitoring | MAGE- Pre | 46.4 percent change of milligrams/deciliter | Standard Error 6.5 |
| Placebo: Protein | Glucose Profiles From Real-Time Continuous Glucose Monitoring | Mean Glucose- Pre | 107.1 percent change of milligrams/deciliter | Standard Error 5.3 |
| Placebo: Protein | Glucose Profiles From Real-Time Continuous Glucose Monitoring | Mean Glucose-Post | 108.6 percent change of milligrams/deciliter | Standard Error 2 |
Secondary
Intracellular Signaling Proteins
Protein content of intracellular signaling proteins that are implicated in mitochondrial biogenesis, mitochondrial function and insulin sensitivity were measured by Western blotting. Densitometry results are reported as a ratio of protein divided by total amount of protein expressed. All proteins of interest are expressed as phosphorylated relative to total. These data are reported as the percent change from baseline compared to 12 weeks.
Time frame: Baseline and 12 weeks
Population: Proteins were analyzed in a subset of participants due to limited tissue availability.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metformin: Carbohydrate | Intracellular Signaling Proteins | Ratio of AKT S473 phospho/total) | 154.3 percent change of densitometry ratio | Standard Error 46.7 |
| Metformin: Carbohydrate | Intracellular Signaling Proteins | ratio of AKT T308 phospho /total) | 151.8 percent change of densitometry ratio | Standard Error 43.2 |
| Metformin: Carbohydrate | Intracellular Signaling Proteins | RPS6 ratio of phospho/total | 16.6 percent change of densitometry ratio | Standard Error 12.6 |
| Metformin: Carbohydrate | Intracellular Signaling Proteins | 4EBP1 ratio of phospho/total | 35 percent change of densitometry ratio | Standard Error 25.2 |
| Placebo:Carbohydrate | Intracellular Signaling Proteins | ratio of AKT T308 phospho /total) | 563.2 percent change of densitometry ratio | Standard Error 230.1 |
| Placebo:Carbohydrate | Intracellular Signaling Proteins | RPS6 ratio of phospho/total | -2.2 percent change of densitometry ratio | Standard Error 25.4 |
| Placebo:Carbohydrate | Intracellular Signaling Proteins | 4EBP1 ratio of phospho/total | 57 percent change of densitometry ratio | Standard Error 42 |
| Placebo:Carbohydrate | Intracellular Signaling Proteins | Ratio of AKT S473 phospho/total) | 677.5 percent change of densitometry ratio | Standard Error 187.5 |
| Metformin: Protein | Intracellular Signaling Proteins | RPS6 ratio of phospho/total | 47.0 percent change of densitometry ratio | Standard Error 16.5 |
| Metformin: Protein | Intracellular Signaling Proteins | ratio of AKT T308 phospho /total) | 477.3 percent change of densitometry ratio | Standard Error 148.2 |
| Metformin: Protein | Intracellular Signaling Proteins | 4EBP1 ratio of phospho/total | 122 percent change of densitometry ratio | Standard Error 76 |
| Metformin: Protein | Intracellular Signaling Proteins | Ratio of AKT S473 phospho/total) | 321.1 percent change of densitometry ratio | Standard Error 147.4 |
| Placebo: Protein | Intracellular Signaling Proteins | 4EBP1 ratio of phospho/total | 13.5 percent change of densitometry ratio | Standard Error 13.9 |
| Placebo: Protein | Intracellular Signaling Proteins | ratio of AKT T308 phospho /total) | 94.0 percent change of densitometry ratio | Standard Error 25.4 |
| Placebo: Protein | Intracellular Signaling Proteins | Ratio of AKT S473 phospho/total) | 106.9 percent change of densitometry ratio | Standard Error 28.8 |
| Placebo: Protein | Intracellular Signaling Proteins | RPS6 ratio of phospho/total | -15.6 percent change of densitometry ratio | Standard Error 15.4 |