Barriers to Physical Activity in People With Type 2 Diabetes

Exercise is a potent therapy to reduce cardiovascular mortality in Type 2 Diabetes (T2D).
Although exercise is a cornerstone of treatment for T2D, people with T2D are more sedentary
than similarly obese people without diabetes, for reasons that are unclear. Interventions
which combined behavioral support and physical activity prescriptions successfully increased
physical activity levels for people with T2D and at-risk for T2D. However, the program
components which mediated increased physical activity were combined and thus the individual
benefits of each component remain unknown. Given the success of these combined programs, it
appears behavioral support and other psychological factors may play an important role. The
study investigators are interested in the predictors of physical activity adherence in T2D as
key targets for future interventions.

One likely factor which may influence physical activity adherence is perceived exercise
effort. The study investigators reported, based on a small study, that perceived exercise
effort is worse in people with T2D than in healthy obese controls, as measured by the Borg
Rating of Perceived Exertion (RPE), even during low intensity exercise. Thus, one strategy to
increase physical activity in T2D is to first identify the mediators of RPE in the proposed
study and then to address them in future studies. The preliminary data suggest that likely
mediators of RPE are both objective and subjective in nature. A key objective mediator of RPE
is serum lactate level during exercise, which is a physiological marker of effort, and is
disproportionately elevated in people with T2D vs. healthy controls. A key subjective
mediator of RPE is self-efficacy, which influences the perception of exercise effort, and is
disproportionately worse in people with T2D vs. healthy controls. To develop optimal physical
activity interventions for people with T2D, the study investigators must understand whether
RPE differences vary across the spectrum of exercise intensities (Aim 1), and the
investigators must also determine the mediators of RPE across exercise intensities (Aim 2).
Mediators of RPE in low-to-moderate intensity exercise are particularly important, because
walking is a preferred physical activity for people with T2D.

Inclusion Criteria:

- Sedentary men and women not participating in a regular exercise program (> 60 minutes
of exercise per week)

- If subject has diabetes,

- must be uncomplicated type 2 diabetes (T2D) and

- <15 years since T2D diagnosis.

- Ages of 50-70 years

- BMI between 25 and 35

- Subjects can only be taking the following oral hypoglycemic drugs:

- metformin,

- sulfonylureas or

- sitagliptin.

- Persons with T2D only if they have total glycosylated hemoglobin levels (HbA1C) <8.0%
(adequate control) on therapy.

- Control subjects must have:

- HbA1C < 5.7% and

- a fasting blood glucose of <100 mg/dl suggesting no significant insulin
resistance.

- All women must be post-menopausal, documented by menstrual history and follicle
stimulating hormone (FSH) level.

- Those who have quit smoking for at least 1 year will be accepted.

- Absence of comorbid conditions that could affect exercise will be confirmed by
history, physical examination and laboratory testing.

Exclusion Criteria:

- Persons with clinically evident distal symmetrical neuropathy, determined by
evaluation of symptoms (numbness, paresthesia) and signs (elicited by vibration,
pinprick, light touch, ankle jerks), will be excluded from further study as neuropathy
may limit exercise performance.

- Specifically, if monofilament sensation is absent at the level of the ankles,
then participants will be excluded from study participation.

- Persons with autonomic dysfunction (>20 mm fall in upright BP without a change in
heart rate) will be excluded as well, due to associated limitations of exercise
performance.

- Current use of insulin or other oral hypoglycemic medications.

- Current smokers will be excluded since smoking can impair cardiovascular (CV) exercise
performance

- Persons will be excluded if they have:

- evidence of heart disease by history (Prior heart attack or bypass surgery, heart
failure, or significant valvular disease) or

- abnormal resting electrocardiogram (EKG) consistent with prior infarct or latent
ischemia (unless cardiovascular stress imaging or catheterization shows they do
not have coronary artery disease).

- left or right bundle branch block on resting EKG (precludes recognition of
ischemic EKG changes with exercise) or

- abnormal exercise EKG (> 1 mm ST segment depression 80 msec out in the ST segment
for 3 consecutive beats).

- Persons with angina or any other exercise-limiting cardiovascular, pulmonary or
musculoskeletal symptoms.

- Presence of:

- systolic blood pressure >145 mm Hg at rest or >250 mm Hg with exercise or

- diastolic blood pressure >90 mm Hg at rest or >115 mm Hg with exercise.

- Subjects with:

- proteinuria (urine protein >220 mg/dl) or

- creatinine > 1.6 mg/dl, suggestive of renal disease.

- Subjects with:

- total cholesterol >220 mg/dl,

- low density lipoprotein > 130 mg/dl, or

- triglycerides > 250 mg/dl, will be excluded given the potential insulin
resistance and endothelial dysfunction associated with these cholesterol
parameters.

- Control subjects who have more than two immediate family members with type 2 diabetes.

- Chronic obstructive pulmonary disease demonstrated by a ratio of

- Forced Expiratory Volume in 1 second (FEV1),

- Forced Vital Capacity (FVC) < 0.70, or

- FEV1 <70% predicted during spirometry.

- Persons weighing more than 300 pounds will be excluded as this exceeds the weight
capacity of our Dual Energy X-ray Absorptiometry device

- Participants with moderate cognitive impairment (Folstein Mini-Mental Status
Examination (MMSE) score <24).