Effect of Insulin Sensitizer Therapy on Atherothrombotic and Inflammatory Profiles Associated With Insulin Resistance
Condition: Type 2 Diabetes; Insulin Resistance; Metabolic Syndrome
MeSH terms: Metabolic Syndrome; Insulin Resistance
Intervention: metformin; pioglitazone; Placebo
Intervention description: To minimize side effects the metformin will be initiated at 500 mg twice daily with meals and increased to 1 gm twice daily with meals after two weeks and continue to a total of 3 months of dosing.; To minimize side effects, the pioglitazone will be initiated at 30 mg daily and increased to 45 mg daily after two weeks, and continue to a total of 3 months of dosing.; Placebo tablets matching the metformin and pioglitazone tablets are given in the same regimen as the active drug arm for 3 months.
Intervention MeSH terms: Metformin; Pioglitazone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 28.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Inflammatory cytokine; Cardiovascular Disease; Thrombotic factors; Dyslipidemia

Summary:

      The objective of this study is to determine whether targeted pharmacological improvement of
      insulin sensitivity will normalize the associated elevations of thrombotic and inflammatory
      cardiovascular disease (CVD) biomarkers in individuals with insulin resistance.
    

Eligibility criteria:

        Inclusion criteria:

          -  We will study 30 patients with Type 2 Diabetes or impaired fasting glucose (15 men &
             15 women) who are > 20 years old.

          -  Only patients who use lifestyle modification to manage their diabetes and are not on
             any oral hypoglycemic agents or insulin will be included.

          -  We will enroll subjects who have fasting glucose concentration greater than 100 mg/dl
             on two consecutive occasions and have a Body Mass Index between 27-36 kg/m^2.

        Exclusion Criteria:

          -  We will exclude patients whose blood glucose is above 180 mg/dl. This will avoid the
             need to perform home glucose monitoring and the potential of unblinding the study by
             the volunteers.

          -  Patients taking oral hypoglycemic agents or insulin would be excluded.

          -  Any diseases such as active cardiovascular disease, liver diseases, kidney failure
             (males with serum creatinine >= 1.5mg/dl, females >=1.4 mg/dl), active
             endocrinopathies, debilitating chronic disease, anemia, symptoms of undiagnosed
             illness, history of alcoholism (alcohol use > 4oz/day) or substance abuse, chronic
             neurological diseases including Alzheimer's disease, stroke, etc, myopathies or any
             other active disease that may potentially affect the outcome measures.

          -  Patients on medicines such as beta blockers, corticosteroids, tricyclics,
             benzodiazepines, opiates, barbiturates, anticoagulants and any other drugs or
             preparations that may affect mitochondrial function will be excluded.

          -  People allergic to any of the class of drug such as lidocaine will also be excluded.

          -  People with pacemakers, certain aneurysm clips and claustrophobia will also be
             excluded as they cannot undergo magnetic resonance imaging.