Impaired Glucose Tolerance (Prediabetes), Type 2 Diabetes Mellitus
Conditions
Brief summary
Diabetes and its associated complications affect more than 20 million Americans, and the prevalence of type 2 diabetes and impaired glucose tolerance rises dramatically with age such that 40% of Americans over age 60 are affected. In older adults, glucose metabolism may be affected by reduced skeletal muscle capillary supply, which limits insulin, glucose, and oxygen delivery to skeletal muscle. Reduced capillary supply to skeletal muscle is found in older individuals with impaired glucose tolerance and we hypothesize that this is due to reduced vascular growth factor expression, and chronic inflammation. Further, we hypothesize that reversal of a sedentary lifestyle through aerobic exercise training will increase insulin signaling and vascular growth factor expression, as well as decrease inflammation, to increase capillary supply to skeletal muscle, which contributes to improved glucose metabolism in older adults. This study will: 1) Determine the mechanisms underlying reduced skeletal muscle capillarization in older adults with impaired glucose tolerance; and 2) Determine the effect of aerobic exercise training-induced increases in skeletal muscle capillarization on glucose metabolism in older adults.
Interventions
BEHAVIORALAerobic exercise training
24 weeks of aerobic exercise training: 3 times per week, 60 minutes per session, at 70% of maximal aerobic capacity
BEHAVIORALDetraining (cessation of exercise)
Cessation of exercise for 2 weeks
Sponsors
University of Maryland
National Institutes of Health (NIH)
National Institute on Aging (NIA)
US Department of Veterans Affairs
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 50-75 years * Non-smoker \>2 years * Body mass index = 18-35 kg/m2
Exclusion criteria
* History of CAD or cerebrovascular disease that would preclude exercise * Implantable defibrillator * Active cancer * Chronic pulmonary, thyroid, renal, liver, or hematological disease * HIV positive or prone to malnutrition * Sickle cell anemia * Type 1 diabetes, or currently on medication to treat type 2 diabetes * Poorly-controlled type 2 diabetes * Poorly-controlled hypertension * Taking medications including: beta-blockers, oral steroids, warfarin, certain statins, hormone replacement therapy (HRT), oral contraceptives (OCP), thiazolidinediones (TZD), or chronic steroids or nonsteroidal analgesics (NSAIDS) that may not be safely discontinued temporarily for specific procedures (i.e. for 72 hours prior) * Allergic to lidocaine or heparin * Recent weight change (\>5kg in 3 months) * Currently pregnant or nursing * Physical impairment limiting exercise * Dementia or unstable clinical depression
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Glucose Utilization | baseline | Insulin-stimulated glucose uptake |
| Glucose Utilization (Pre/Post Intervention) | baseline, 24 weeks, 26 weeks | Insulin-stimulated glucose uptake |
| Baseline Skeletal Muscle Capillarization | baseline | — |
| Skeletal Muscle Capillarization (Pre/Post Intervention) | baseline, 24 weeks, 26 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Baseline 2-hour Postprandial Glucose | baseline | — |
| Body Composition (%Fat) | baseline, 24 weeks | — |
| 2-hr Post-prandial Plasma Glucose Level | baseline, 24 weeks, 26 weeks | — |
| Baseline Cardiorespiratory Fitness | baseline | maximal oxygen consumption |
| Cardiorespiratory Fitness | baseline, 24 weeks, 26 weeks | Maximal oxygen consumption |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Older Adults - Normal Glucose Tolerance Normal Glucose Tolerance | 19 |
| Older Adults - Impaired Glucose Tolerance Impaired Glucose Tolerance | 12 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Exercise Intervention | time conflict; non-study related illness | 0 | 5 | 3 |
| Screening | Failed Screening | 40 | 0 | 0 |
| Screening | Time conflicts | 19 | 0 | 0 |
Baseline characteristics
| Characteristic | Older Adults - Normal Glucose Tolerance | Older Adults - Impaired Glucose Tolerance | Total |
|---|---|---|---|
| Age, Continuous | 60 years STANDARD_DEVIATION 7 | 60 years STANDARD_DEVIATION 8 | 60 years STANDARD_DEVIATION 7 |
| Sex: Female, Male Female | 9 Participants | 6 Participants | 15 Participants |
| Sex: Female, Male Male | 10 Participants | 6 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 90 |
| serious Total, serious adverse events | 0 / 90 |
Outcome results
Primary
Baseline Glucose Utilization
Insulin-stimulated glucose uptake
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Older Adults - Normal Glucose Tolerance | Baseline Glucose Utilization | 0.0062 µmol/kgFFM/pmol insulin/min | Standard Error 0.00008 |
| Older Adults - Impaired Glucose Tolerance | Baseline Glucose Utilization | 0.0035 µmol/kgFFM/pmol insulin/min | Standard Error 0.0004 |
Primary
Baseline Skeletal Muscle Capillarization
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Older Adults - Normal Glucose Tolerance | Baseline Skeletal Muscle Capillarization | 313 capillaries/mm2 | Standard Error 13 |
| Older Adults - Impaired Glucose Tolerance | Baseline Skeletal Muscle Capillarization | 246 capillaries/mm2 | Standard Error 8 |
Primary
Glucose Utilization (Pre/Post Intervention)
Insulin-stimulated glucose uptake
Time frame: baseline, 24 weeks, 26 weeks
Population: Glucose tolerance data were analyzed as a continuous variable (combining Arms) as opposed to categorical (i.e., within each Arm) due to the sample size of this pilot study; thus, data are reported for the entire group of participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Adults - Normal Glucose Tolerance | Glucose Utilization (Pre/Post Intervention) | Baseline | 0.041 µmol/kgFFM/pmol insulin/min | Standard Error 0.005 |
| Older Adults - Normal Glucose Tolerance | Glucose Utilization (Pre/Post Intervention) | 24-week | 0.052 µmol/kgFFM/pmol insulin/min | Standard Error 0.006 |
| Older Adults - Normal Glucose Tolerance | Glucose Utilization (Pre/Post Intervention) | 26-week | 0.048 µmol/kgFFM/pmol insulin/min | Standard Error 0.005 |
Primary
Skeletal Muscle Capillarization (Pre/Post Intervention)
Time frame: baseline, 24 weeks, 26 weeks
Population: Glucose tolerance data were analyzed as a continuous variable (combining Arms) as opposed to categorical (i.e., within each Arm) due to the sample size of this pilot study; thus, data are reported for the entire group of participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Adults - Normal Glucose Tolerance | Skeletal Muscle Capillarization (Pre/Post Intervention) | Baseline | 289 capillaries/mm2 | Standard Error 12 |
| Older Adults - Normal Glucose Tolerance | Skeletal Muscle Capillarization (Pre/Post Intervention) | 24-week | 341 capillaries/mm2 | Standard Error 21 |
| Older Adults - Normal Glucose Tolerance | Skeletal Muscle Capillarization (Pre/Post Intervention) | 26-week | 361 capillaries/mm2 | Standard Error 10 |
Secondary
2-hr Post-prandial Plasma Glucose Level
Time frame: baseline, 24 weeks, 26 weeks
Population: Glucose tolerance data were analyzed as a continuous variable (combining Arms) as opposed to categorical (i.e., within each Arm) due to the sample size of this pilot study; thus, data are reported for the entire group of participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Adults - Normal Glucose Tolerance | 2-hr Post-prandial Plasma Glucose Level | Baseline | 173 mg/dL | Standard Error 8 |
| Older Adults - Normal Glucose Tolerance | 2-hr Post-prandial Plasma Glucose Level | 24-week | 153 mg/dL | Standard Error 16 |
| Older Adults - Normal Glucose Tolerance | 2-hr Post-prandial Plasma Glucose Level | 26-week | 142 mg/dL | Standard Error 19 |
Secondary
Baseline 2-hour Postprandial Glucose
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Older Adults - Normal Glucose Tolerance | Baseline 2-hour Postprandial Glucose | 107 mg/dl | Standard Error 2 |
| Older Adults - Impaired Glucose Tolerance | Baseline 2-hour Postprandial Glucose | 160 mg/dl | Standard Error 10 |
Secondary
Baseline Cardiorespiratory Fitness
maximal oxygen consumption
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Older Adults - Normal Glucose Tolerance | Baseline Cardiorespiratory Fitness | 2.2 L/min | Standard Error 0.3 |
| Older Adults - Impaired Glucose Tolerance | Baseline Cardiorespiratory Fitness | 1.7 L/min | Standard Error 0.2 |
Secondary
Body Composition (%Fat)
Time frame: baseline, 24 weeks
Population: Glucose tolerance data were analyzed as a continuous variable (combining Arms) as opposed to categorical (i.e., within each Arm) due to the sample size of this pilot study; thus, data are reported for the entire group of participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Adults - Normal Glucose Tolerance | Body Composition (%Fat) | Baseline | 35 percentage of fat | Standard Error 3 |
| Older Adults - Normal Glucose Tolerance | Body Composition (%Fat) | 24-week | 33 percentage of fat | Standard Error 3 |
Secondary
Cardiorespiratory Fitness
Maximal oxygen consumption
Time frame: baseline, 24 weeks, 26 weeks
Population: Glucose tolerance data were analyzed as a continuous variable (combining Arms) as opposed to categorical (i.e., within each Arm) due to the sample size of this pilot study; thus, data are reported for the entire group of participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Adults - Normal Glucose Tolerance | Cardiorespiratory Fitness | 26-week | 2.2 L/Min | Standard Error 0.5 |
| Older Adults - Normal Glucose Tolerance | Cardiorespiratory Fitness | 24-week | 2.3 L/Min | Standard Error 0.5 |
| Older Adults - Normal Glucose Tolerance | Cardiorespiratory Fitness | Baseline | 1.8 L/Min | Standard Error 0.1 |