Diabetes, Physical Activity
Conditions
Keywords
Neuropathy, diabetes
Brief summary
The purpose of this study is to determine if an individually tailored diet and physical enhancement program can improve mobility, physical activity, and neuropathy in people with early diabetes.
Detailed description
Neuropathy is the most common complication of diabetes mellitus. Impaired glucose regulation (IGR) is associated with development of peripheral neuropathy coupled with gait and mobility impairment that may be disabling for the patient. Recent novel data from the investigators' group indicates that improved diet and exercise can significantly improve and even reverse neuropathy associated with IGR, however this has not been tested as a specific intervention in a controlled diabetes complications trial. IGR includes patients with early type 2 diabetes mellitus (T2DM), impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) based on standardized criteria for the diagnosis of T2DM. The investigators hypothesize that, compared to IGR participants advised to follow the current standard care recommendations on diet and exercise (Standard Care or SC), IGR participants undergoing a Tailored Diet and Physical Activity (TDPA) enhancement program will show greater improvement in the 6 minute walk test (6MW) and will show a greater reduction in markers of neuropathy progression e.g. intraepidermal nerve fiber density (IEFND). Furthermore, the investigators will test the hypothesis that improvement in measures of neuropathy, mobility function and physical activity (PA) will correlate strongly with each other and with improvement in specific measures of metabolic function, and weight loss. This proposal will permit us to determine if TDPA can improve mobility and induce nerve regeneration in subjects with early diabetes.
Interventions
BEHAVIORALTailored Diet and Physical Activity
Subjects will receive an individually tailored diet and physical activity enhancement program
BEHAVIORALStandard of Care
Subjects will be told to reduce their baseline weight by 7% and exercise for 150 minutes/week. There is no tailored, directed program.
Sponsors
University of Maryland, College Park
University of Michigan
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
double blind
Intervention model description
parallel treatments
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* IGR at the time of screening or within three months of screening. This definition includes patients with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and early diabetes. Patients can be included if they have an increased risk for diabetes with a HBA1C \> or = 5.7% (using a method certified by the National Glycohemoglobin Standardization Program), or they have diabetes with a HBA1C \> or equal to 6.5%, or an abnormal fasting venous glucose, or abnormal venous glucose values following a 75 gram oral load. Glucose values are as defined (mg/dl): IFG fasting greater than 100 mg/dl, IGT- fasting less than 126, 2 h 140-199, or diabetes - fasting glucose \> 126, 2 h \> 200 based on the Standards for Medical Care in Diabetes 2010 by the American Diabetes Association. * The HbA1c may be normal, but must be \<8%. * If diabetic subjects are on medication, they should be stable on medication for at least 3 months prior to entering the study. Addition or change in antidiabetic medications after enrollment does not affect participation or group assignment. * No risk factors for other causes for neuropathy (determined by a medical history, family history, history of medications, occupational history, history of exposure to toxins, physical and neurological examinations, and laboratory studies). * Clinical signs or symptoms of neuropathy as determined by the treating neurologists history and physical exam, plus an abnormality of one of the following: nerve conduction studies (NCS), Quantitative Sudomotor Autonomic Reflex Testing (QSART), Quantitative Sensory Testing (QST), or IENFD. * Age range from 30 to 80 years inclusive at the time of screening * Medically stable at the time of enrollment. * Able to participate in a standing exercise program without constant standby monitoring. * Women of childbearing potential must be using an acceptable method of contraception to prevent pregnancy when they are enrolled in the study and must agree to continue to practice an acceptable method of contraception for the duration of their participation in the study. * Patient must agree to taking an alternative medication to coumadin when undergoing a skin biopsy * Willing to complete weekly self-report questionnaires. * Willing to accept assignment to either training group. * Willing and able to increase activity level and exercise independently at home.
Exclusion criteria
* Pregnant women, prisoners, institutionalized subjects and other at risk subjects will not be included in this study. * Taking insulin. * Etiology of sensorimotor neuropathy other than IGR based on careful clinical and laboratory evaluation. * Current severe medical conditions that are active on the day of enrollment and would affect a patient's ability to complete study. This may include active advanced current ischemic heart disease (e.g., angina or congestive heart failure), permanent residual lower extremity weakness or loss of balance resulting from a stroke, active severe obstructive or restrictive pulmonary disease, ongoing cancer treatment, renal failure currently requiring dialysis, or severe ongoing peripheral vascular disease. * An inability to understand or cooperate with the procedures of the trial or refusal to sign the informed consent. * Patients who are unable to answer questions correctly on the Evaluation to Sign Consent (ESC) tool. * Significant other neurologic, rheumatological, neuromuscular, or other extremity conditions that limit safe exercise or weight bearing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Six Minute Walk (6MW) Test | Six Months | Measures distance covered by participant when walking at a brisk pace without running for six minutes in feet. |
| Change in 6-Minute-Walk Test Measured in Feet Between Baseline and 12 Months | Baseline and 12 Months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intraepidermal Nerve Fiber Density (Distal Leg) | 12 Months | Measure of the number of skin fibers/mm in the lower extremity (distal leg) at 12 months |
| Intraepidermal Nerve Fiber Density (IENFD) at the Proximal Thigh | 12 Months | Measure of the number of skin fibers/mm in the lower extremity (proximal thigh) at 12 months |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Physical Activity (PA) at 12 Months as Measured by the CHAMPS (Community Health Activities Model Program for Seniors) Activity Scale | Baseline and 12 Months | Physical Activity measured by CHAMPS provides an estimated caloric expenditure of subject based on weight and weekly physical activity, as assessed by the questionnaire. Change in physical activity is determined by the difference in daily caloric expenditure at baseline and 12 months. |
Countries
United States
Participant flow
Pre-assignment details
Participants were excluded from the study prior to assignment for groups (n=12) due to failure of screening (e.g. not meeting inclusion/exclusion criteria, n=10) or declined to participate (n=2.)
Participants by arm
| Arm | Count |
|---|---|
| Tailored Diet and Physical Activity Subjects will receive an individually tailored diet and physical activity enhancement program | 32 |
| Standard of Care Subjects will be told to reduce their baseline weight by 7% and exercise for 150 minutes/week. There is no tailored, directed program. | 40 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 7 |
Baseline characteristics
| Characteristic | Standard of Care | Tailored Diet and Physical Activity | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 14 Participants | 26 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 18 Participants | 46 Participants |
| Age, Continuous | 61.03 Years STANDARD_DEVIATION 7.83 | 61.81 Years STANDARD_DEVIATION 8.25 | 61.38 Years STANDARD_DEVIATION 7.91 |
| BMI (Body Mass Index), Categorical BMI 30 - 40 kg/m^2 | 19 Participants | 12 Participants | 31 Participants |
| BMI (Body Mass Index), Categorical BMI < 30 kg/m^2 | 19 Participants | 13 Participants | 32 Participants |
| BMI (Body Mass Index), Categorical BMI > 40 kg/m^2 | 2 Participants | 7 Participants | 9 Participants |
| BMI (Body Mass Index), Continuous | 30.83 kg/m^2 STANDARD_DEVIATION 7.06 | 33.21 kg/m^2 STANDARD_DEVIATION 7.65 | 31.89 kg/m^2 STANDARD_DEVIATION 7.37 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 5 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 30 Participants | 26 Participants | 56 Participants |
| Sex: Female, Male Female | 13 Participants | 11 Participants | 24 Participants |
| Sex: Female, Male Male | 27 Participants | 21 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 32 | 0 / 40 |
| other Total, other adverse events | 1 / 32 | 0 / 40 |
| serious Total, serious adverse events | 0 / 32 | 0 / 40 |
Outcome results
Primary
Change in 6-Minute-Walk Test Measured in Feet Between Baseline and 12 Months
Time frame: Baseline and 12 Months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tailored Diet and Physical Activity | Change in 6-Minute-Walk Test Measured in Feet Between Baseline and 12 Months | 188.415845 feet | Standard Error 34.346235 |
| Standard of Care | Change in 6-Minute-Walk Test Measured in Feet Between Baseline and 12 Months | 100.559319 feet | Standard Error 36.399507 |
Primary
Six Minute Walk (6MW) Test
Measures distance covered by participant when walking at a brisk pace without running for six minutes in feet.
Time frame: Six Months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tailored Diet and Physical Activity | Six Minute Walk (6MW) Test | 156.644156 feet | Standard Error 35.364227 |
| Standard of Care | Six Minute Walk (6MW) Test | 61.257846 feet | Standard Error 35.840649 |
Secondary
Intraepidermal Nerve Fiber Density (Distal Leg)
Measure of the number of skin fibers/mm in the lower extremity (distal leg) at 12 months
Time frame: 12 Months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tailored Diet and Physical Activity | Intraepidermal Nerve Fiber Density (Distal Leg) | 1.28627099 fibers/mm | Standard Error 0.81830712 |
| Standard of Care | Intraepidermal Nerve Fiber Density (Distal Leg) | -0.38943425 fibers/mm | Standard Error 0.84781677 |
Secondary
Intraepidermal Nerve Fiber Density (IENFD) at the Proximal Thigh
Measure of the number of skin fibers/mm in the lower extremity (proximal thigh) at 12 months
Time frame: 12 Months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tailored Diet and Physical Activity | Intraepidermal Nerve Fiber Density (IENFD) at the Proximal Thigh | 1.53825016 fibers/mm | Standard Error 0.83395303 |
| Standard of Care | Intraepidermal Nerve Fiber Density (IENFD) at the Proximal Thigh | -0.54419990 fibers/mm | Standard Error 0.87926529 |
Other Pre-specified
Change in Physical Activity (PA) at 12 Months as Measured by the CHAMPS (Community Health Activities Model Program for Seniors) Activity Scale
Physical Activity measured by CHAMPS provides an estimated caloric expenditure of subject based on weight and weekly physical activity, as assessed by the questionnaire. Change in physical activity is determined by the difference in daily caloric expenditure at baseline and 12 months.
Time frame: Baseline and 12 Months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tailored Diet and Physical Activity | Change in Physical Activity (PA) at 12 Months as Measured by the CHAMPS (Community Health Activities Model Program for Seniors) Activity Scale | -735.249060 kcal/day | Standard Error 886.986 |
| Standard of Care | Change in Physical Activity (PA) at 12 Months as Measured by the CHAMPS (Community Health Activities Model Program for Seniors) Activity Scale | 296.998122 kcal/day | Standard Error 937.93599 |