PGC-1 & MUSCLE MITOCHONDRIAL DYSFUNCTION IN DIABETES: AIMS 1-4
PGC-1 & MUSCLE MITOCHONDRIAL DYSFUNCTION IN DIABETES: AIMS 1-4
We are trying to understand how insulin (a type of hormone in the body that regulates how the
 body regulates how one metabolizes protein and carbohydrates) and exercise alter proteins
 involved in energy production and metabolism in skeletal muscle.
(Aims 1-3) We are trying to understand how insulin (a type of hormone in the body that
 regulates how the body regulates how one metabolizes protein and carbohydrates) and exercise
 alter proteins involved in energy production and metabolism in skeletal muscle. By studying
 this, they hope to better understand the causes of insulin resistance and Type 2 diabetes
 Insulin is a hormone that is produced normally in the body and causes blood sugar to return
 to normal after eating. Insulin resistance is a state when the body is not using insulin
 correctly, and more insulin is needed to keep blood sugar concentrations normal. Insulin
 resistance can lead to Type 2 diabetes. Type 2 diabetes is a disease in which blood sugar
 levels are too high. Our studies may help to find out why some people develop Type 2 diabetes
 and how exercise may prevent this disease.

 (Aim 4) We are asking patients from aims 1-3 to take part in this research study because they
 have high triglycerides that could be treated anyway with fibrates, and they do not have
 diabetes.

 Triglycerides and cholesterol are the two main kinds of fat that are in blood. People who
 have high triglycerides have some health risks and are sometimes treated with drugs called
 "fibrates". This drug turns on a protein in ones body that controls the activity of some of
 the genes that make it easier for their liver to get rid of triglycerides. We think that
 maybe this same gene, in ones muscle, can lower the ability of genes in ones muscle to
 respond beneficially to exercise, but we don't know if this is true.
Aims 1-3.

 1. Age 30-59

 2. BMI: Lean, BMI less than or equal to 25; Obese, BMI between 30- 50; type 2 diabetic,
 BMI between 30- 50.

 3. Subjects must be able to communicate meaningfully with the investigator and must be
 legally competent to provide written informed consent.

 4. Subjects may be of either sex with age as described in each protocol. Female subjects
 must be non-lactating and will be eligible only if they have a negative pregnancy test
 throughout the study period.

 5. Subjects must range in age as described in each specific protocol.

 6. Subjects must have the following laboratory values:

 1. Hematocrit ≥ 35 vol%

 2. Serum creatinine ≤ 1.6 mg/dl

 3. AST (SGOT) < 2 times upper limit of normal

 4. ALT (SGPT) < 2 times upper limit of normal

 5. Alkaline phosphatase < 2 times upper limit of normal

 6. Triglycerides < 150 mg/dl for nondiabetics (except for Aim 4).

 7. Triglycerides <300 for diabetics (except for Aim 4)

 8. INR ≤ 1.3 Aim 4

 1. Age 30-59 2. BMI: Lean, BMI less than or equal to 25; Obese, BMI between 30- 50. 3.
 Patients may have normal or impaired glucose tolerance. 4. Subjects must be able to
 communicate meaningfully with the investigator and must be legally competent to provide
 written informed consent.

 5. Subjects may be of either sex with age as described in each protocol. Female subjects
 must be non-lactating and will be eligible only if they have a negative pregnancy test
 throughout the study period.

 6. Subjects must have the following laboratory values:

 1. Hematocrit ≥ 35 vol%

 2. Serum creatinine ≤ 1.6 mg/dl

 3. AST (SGOT) < 2 times upper limit of normal

 4. ALT (SGPT) < 2 times upper limit of normal

 5. Alkaline phosphatase < 2 times upper limit of normal

 6. Triglycerides > 300 mg/dl for nondiabetics, > 250 mg/dl for impaired glucose
 tolerance.

 7. INR ≤ 1.3 7. Patients must be prescribed gemfibrozil from their doctor

 Exclusion Criteria:

 -  1. Subjects must not be receiving any of the following medications: thiazide or
 furosemide diuretics, beta-blockers, or other chronic medications with known adverse
 effects on glucose tolerance levels unless the patient has been on a stable dose of
 such agents for the past three months before entry into the study. Subjects may be
 taking a stable dose of estrogens or other hormonal replacement therapy, if the
 subject has been on these agents for the prior three months. Subjects taking systemic
 glucocorticoids are excluded. Patients with type 2 diabetes will be excluded if they
 are taking thiazolidinediones, but may be taking sulfonylureas or other medications
 known to work through effects on insulin sectretion.

 2. Subjects receiving Gemfibrozil must not also be receiving a statin. 3. Subjects
 with a history of clinically significant heart disease (New York Heart Classification
 greater than grade II; more than non-specific ST-T wave changes on the EKG),
 peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea
 on exertion of one flight or less; abnormal breath sounds on auscultation) will not be
 studied.

 4. Recent systemic or pulmonary embolus, untreated high-risk proliferative
 retinopathy, recent retinal hemorrhage, uncontrolled hypertension, systolic BP>180,
 diastolic BP>105, autonomic neuropathy, resting heart rate >100, electrolyte
 abnormalities.