Exercise and Type 2 Diabetes: Gender and Endothelial Function

The objective of the current proposal is to evaluate the importance of blood vessel dysfunction and heart dysfunction to overall exercise impairments in type 2 diabetes and their contribution to the gender differences observed in exercise capacity. Importantly, treatments that improve blood vessel function in persons with type 2 diabetes can be used to directly assess whether impairment in blood vessel function and ultimately exercise performance, can be improved and whether the degree of improvement differs between the sexes.

Hypothesis 1. Uncomplicated type 2 diabetes more adversely affects exercise capacity in women than men.

Hypothesis 2. Blood vessel function and cardiac function are more significantly impaired in women with type 2 diabetes than men and contribute to the gender differences in exercise capacity.

Hypothesis 3. Restoration of blood vessel function will improve exercise capacity more in women than men with type 2 diabetes.

Subjects will come in for a total of seven research visits. Four initial study visits before exercise training for three months and then subjects will repeat the testing.

1. Initial exam. A history and physical exam will be performed. Blood will be drawn for measurements of overall health. Resting electrocardiogram will be obtained. The Low Level Physical Activity Recall (LOPAR) questionnaire will be administered.
2. Dual Energy X-ray Absorptiometry (DEXA) will be carried out during visit two. A familiarization bicycle ergometer test will also be performed on this day.
3. During visit three, a euglycemic clamp will be performed.
4. During visit four, echocardiographic measurements will be made and a diet interview will be performed.
5. On visit five, measures of blood vessel-dependent vasodilation will be performed. Repeated brachial artery diameter and forearm blood flow responses to cuff occlusion will be measured separately on this occasion.
6. On visit six, arterial stiffness will be measured. Subjects will also perform a graded bicycle exercise test.
7. On visit seven, subjects will perform constant level bicycle tests.

Eligibility Criteria:
Inclusion Criteria:

* Men and women between the ages of 30 and 55 years
* Persons with type 2 diabetes taking only certain oral medications (
* Pre-menopausal women
* Persons with type 2 diabetes who have a total HbA1c level \<9%
* Persons with a BMI between 25-35.

Exclusion Criteria:

* Current smokers or anyone who has smoked within the last year
* Persons who have clinically evident distal symmetrical neuropathy
* Abnormal lipid levels (total cholesterol \>200, LDL-cholesterol level \>130, or triglyceride level \>250).
* Persons with regional wall motion abnormalities, left ventricular wall thickness \>1.1 cm , or decreased contractility.
* Persons will also be excluded if they have evidence of ischemic heart disease by history or abnormal resting or exercise electrocardiogram (ECG).
* Presence of systolic blood pressure \>140 mmHg at rest or \>250 mmHg with exercise or diastolic pressure \>90 mmHg at rest or \>105 mmHg with exercise will be grounds for exclusion.
* Subjects will be excluded who have peripheral arterial disease.
* Persons with autonomic insufficiency, assessed by measuring variation in RR intervals with cycled breathing and by presence of a \>20 mm fall in upright blood pressure without a change in heart rate, will be excluded.
* Subjects with proteinuria (urine protein \>200 mg/dl) or a creatinine \> 2 mg/dl, suggestive of renal disease will be excluded.
* Controls will not be accepted with an immediate family history of Type 2 Diabetes Mellitis