Molecular Mechanisms of Type 2 Diabetes Mellitus

Launched by THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO · Dec 31, 2008

Keywords

ClinConnect Summary

Specific Aims

To test the global hypothesis that increases in insulin signaling through either PI-3-kinase or MAP kinase pathways correlate with improvements in NO production or NOS expression in skeletal muscle following pioglitazone therapy, we will determine whether 6 months of Pioglitazone therapy:

i. Increases the activities of muscle NO synthase, IRS-1, PI-3 kinase, PI3-kinase associated with IRS-1 and/or MAP-kinase ii. Improves brachial arterial endothelial function In addition, we will determine whether 6 months of pioglitazone therapy improves abnormal cardiovascular disease risk...

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. male or female 18-65 years of age;
• • 2. type 2 diabetes based on the American Diabetes Association criteria;
• • 3. HbA1c = 6.5-9.0% while on diet alone or diet plus sulfonylurea (or meglitinides) therapy;
• • 4. no history of thiazolidinediones, insulin, ACE inhibitor or AII-receptor blockade therapy;
• • 5. taking no medications known to affect glycemic control or endothelial function, unless the medication has been stable for at least 3 months;
• • 6. blood pressure equal or below 140/90 mmHg;
• • 7. not pregnant and willing to take appropriate contraceptive measures if capable of becoming pregnant;
• • 8. serum creatinine below 1.7 mg/dl in female and 1.8 mg/dl in males;
• • 9. ALT (SGTP) or AST (SGOT) less than 2 times the upper limit of normal for the laboratory and absence of clinical signs or symptoms of liver disease;
• • 10. hematocrit \> 34% in females and \>35% in males;
• • 11. normal thyroid function;
• • 12. no evidence of coronary heart disease (by history or EKG) or moderate to severe congestive heart failure (NY Heart Association Cardiac Class III or IV);
• • 13. no history or the presence of any clinically significant or unstable medical condition that makes the subject unlikely to complete the study in the opinion of the PI; and
• • 14. absence of any condition or situations which would preclude adherence and completion of the protocol;
• • 15. the ability to give voluntary informed consent.
• Exclusion Criteria:
• • 1. Subjects were excluded from study if they had ever received insulin, metformin, TZDs, exenatide or DPP IV inhibitor.
• • 2. All subjects were free of cardiovascular, renal or major organ disease, as determined by medical history, physical examination, screening blood chemistries, complete blood cell count, and electrocardiogram.