Conditions: Metabolic Syndrome
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 17
Healthy volunteers: yes

Brief summary:
The study will be focused on determining the integrated in-vivo mechanisms responsible for Ramipril's effects on delaying type 2 diabetes and restoring normal (blood sugar levels) glycemia in patients with impaired glucose tolerance.

Hypothesis - Ramipril effects will delay the onset of type 2 diabetes and restore normal glycemia in patients with impaired glucose tolerance.

Detailed description:
Several studies have demonstrated that therapeutic agents used to reduce glucose levels and/or weight can delay the onset of type 2 diabetes. Intriguingly, angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) also result in reduction in the onset of type 2 DM. The most striking effect was found with Ramipril in the HOPE study. The onset of new type 2 DM was reduced by 34% (p\<0.001) as compared to placebo. Furthermore, the results of the DREAM trial demonstrate that Ramipril at a dose of 15 mg can significantly reverse impaired glucose tolerance. However, the mechanisms underlying Ramipril effects to delay type 2 diabetes are not known.

The proposal will be focused on determining the integrated in-vivo mechanisms responsible for Ramipril's effects on delaying type 2 DM and restoring normal glycemia in patients with impaired glucose tolerance.

The specific aims of the project are:

* to determine the effect of Ramipril on insulin resistance at the level of the liver and peripheral tissues,
* to determine the effect of Ramipril on endothelial function,
* to determine the effects of Ramipril on insulin secretion, and
* to determine the effects of Ramipril on substrate flux, lipolysis and inflammatory cytokines.

Arms:
arm 1: Patients randomized to 6 months treatment of Ramipril. arm 2: PAtients randomized to 6 months treatment of HCTZ. arm 3: Patients randomized to 6 months treatment of Ramipril+HCTZ.

Interventions: intervention 1: Ramipril intervention 2: HCTZ-hydrochlorothiazide intervention 3: Ramipril+HCTZ
Intervention descriptions: intervention 1: Ramipril 20 mg once daily for 6 months intervention 2: HCTZ 25 mg once daily for 6 months intervention 3: Ramipril 20 mg and HCTZ 25 mg, both once daily for 6 months

Protocol document: