Pioglitazone and Serum Asymmetric Dimethylarginine (ADMA) in Patients With Diabetes

Phase 4

Completed

Interventions: Drug: Placebo then Pioglitazone
Drug: Pioglitazone then Placebo

Brief Summary: SPECIFIC AIMS

1. To determine whether pioglitazone will reduce levels of asymmetric dimethylarginine(ADMA) in patients with diabetes.

2. To determine whether nitric oxide(NOx) products are increased with pioglitazone treatment.

3. To determine whether pioglitazone reduces oxidative stress (F2-isoprostanes).

Detailed Description: The primary purpose of this study is to determine whether treatment with pioglitazone can reduce serum levels of asymmetric dimethylarginine (ADMA) in patients with adult diabetes. Recent research has found that elevated serum ADMA is associated with increased cardiovascular events and mortality, particularly in people with diabetes (Boger 2005, Zoccali 2006, Ueda 2007). ADMA, by mediating nitric oxide (NO) availability, may trigger pro-atherogenic effects. High plasma concentration of this substance has been associated with intima-media thickening, left ventricular hypertrophy and all-cause and cardiovascular mortality in patients with end-stage renal disease, and associated with increased cardiovascular events in patients with diabetes (Kryzazanowska 2007). The result of higher levels of ADMA and reduced output of NO increases vasoconstriction, increases inflammation, and interferes with endothelial function. Preliminary studies indicate that pioglitazone may reduce ADMA levels, and thus lower cardiovascular risk.Thus, this protocol will test whether pioglitazone can reduce ADMA levels in adult patients with diabetes.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Any history of known coronary heart disease, including a history of congestive heart failure, myocardial infarction, coronary re-vascularization, or stroke
Pregnancy
Chronic kidney disease, serum creatinine >2.0mg/dl, chronic liver disease, or uncontrolled hypertension (>160/100).
Current participation in a formal weight loss program or planning to start such a program during the next 3 months
Collagen vascular disease, infection, or other inflammatory condition
Electrocardiogram (EKG) evidence of ischemia or infarction
Macular edema (swelling of the back of the eye), recent excessive weight gain (over 5% of weight in 30 days), elevated liver function tests > 2.5 X the upper limit, or history of osteoporosis

Arm && Interventions

Group	Intervention	Description
Placebo then Pioglitazone	Placebo then Pioglitazone	18 (other half of participants) volunteers that are Diabetic adults, 40-75 years that have higher ADMA levels as well as increased inflammation will take the placebo for the first 12 week period of the study and then take the Pioglitazone for the final 12 weeks of the study.
Pioglitazone then Placebo	Pioglitazone then Placebo	18 volunteers that are Diabetic adults, 40-75 years that have higher ADMA levels as well as increased inflammation will take Pioglitazone for the first 12 week period of the study and then take the placebo for the final 12 weeks of the study.

Primary Outcome Measures

Name	Time	Method
Asymmetric Dimethylarginine (ADMA) Level	3 months	Labs measured micro moles per liter of ADMA levels in participants.

Secondary Outcome Measures

Name	Time	Method
NOx f2-isoprostanes	3 months	Measured oxidative stress - NOx measured by chemiluminescence detection using the Sievers NOA 280i and f2-isoprostanes are isolated by thin layer chromatography and subjected to a highly sensitive and specific gas chromatography/mass spectroscopy method to measusre the oxidative stress