What Makes Exercise Feel More Difficult to Women With and Without Type 2 Diabetes

Inclusion Criteria:

- Sedentary women not participating in a regular exercise program (> one bout of
exercise per week)

- If subject has diabetes, must be uncomplicated T2DM and < 25 years since T2DM
diagnosis

- Ages of 50-70 years

- BMI of 25-35

- Subjects can only be taking the following oral hypoglycemic drugs: metformin,
sulfonylureas or sitagliptin. Use of insulin or other oral hypoglycemic medications is
not allowed.

- Persons with T2DM will be accepted for study only if they have total glycosylated
hemoglobin levels (HbA1C) <8% (adequate control) on therapy.

- Control subjects must have HbA1C < 5.5% 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.

- Current smokers will be excluded since smoking can impair CV exercise performance but
people who have quit smoking for at least 1 year will be accepted for study.

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

Exclusion Criteria:

- In general, people will be excluded with any condition which could limit exercise
performance.

- 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.

- 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.

- 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). We will also exclude subjects with 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 will be excluded as well.

- Presence of systolic blood pressure >150 at rest or >250 with exercise or diastolic
pressure >95 at rest or >105 with exercise are also grounds for exclusion.

- Subjects with proteinuria (urine protein >200 mg/dl) or a creatinine > 2 mg/dl,
suggestive of renal disease will be excluded.

- 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.

- Subjects taking the following medications will be excluded: insulin, oral hypoglycemic
agents other than those stated in inclusion criteria, estrogen-containing hormone
replacement therapy including the "estring".

- Control subjects who have an immediate family member with type 2 diabetes will be
excluded.