OBJECTIVE -Angiotensin II has been shown to increase hepatic glucose production and decrease insulin sensitivity. Patients who utilize either an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) may experience a decreased incidence of new-onset type 2 diabetes. RESEARCH DESIGN AND METHODS-Three reviewers conducted a systematic literature search of Medline, EMBASE, CINAHL, and the Cochrane Library (1966 to present) to extract a consensus of trial data involving an ACEI or ARB with an end point of new-onset type 2 diabetes. Studies were included if they were randomized controlled trials verses placebo/ routine therapy. A random-effects model was utilized. Subgroup and sensitivity analyses were conducted. . No statistical heterogeneity was observed for any evaluation (P Ͼ 0.1 for all comparisons). ACEIs and ARBs did not reduce the odds of mortality, cardiovascular, or cerebrovascular events versus control therapy among all of these studies combined or the hypertension trials. ACEIs and ARBs did reduce the odds of these outcomes among the coronary artery disease studies versus control therapy. RESULTSCONCLUSIONS -ACEIs or ARBs may decrease patients' odds of developing new-onset type 2 diabetes but does not reduce the odds of mortality, cardiovascular, or cerebrovascular outcomes over the study follow-up periods among patients with hypertension. Diabetes Care 28:2261-2266, 2005G iven the elevated risk of morbidity and mortality among patients with type 2 diabetes, prevention of type 2 diabetes is a worthwhile goal. Substantive weight loss eliminates insulinresistant fatty tissue and reduces the risk of progressing from impaired glucose tolerance to full-blown type 2 diabetes by 37-58% (1). Metformin and thiazolidinedione therapy also reduces the rate of type 2 diabetes onset among patients with impaired glucose tolerance or gestational diabetes history by 31-55% (1).ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been used for years to reduce the rate of diabetic nephropathy progression in patients with type 2 diabetes (2). In addition, ACEIs and ARBs enhance insulin sensitivity and therefore benefit patients at high risk of developing type 2 diabetes. ACEIs improved the insulin sensitivity index by 12.1 Ϯ 15.8% in a compilation of 20 pharmacologic trials, while ARBs raised the insulin sensitivity index by 18.7 Ϯ 17.9% in a compilation of 9 pharmacologic trials (1).ACEIs and ARBs have been studied versus placebo or control therapy in numerous clinical trials of patients who had hypertension, coronary artery disease, or chronic heart failure. In secondary subgroup analyses, the impact of ACEI or ARB usage on the development of newonset type 2 diabetes has been evaluated. While many trials showed significant benefits in preventing new-onset type 2 diabetes, several other trials did not (3-17). One way to reconcile these clinical trial differences is through the use of meta-analysis. Meta-analysis allows incorporation of data from several studies into a single analysis with increased power ...

Mice pretreated with the peroxisome proliferator clofibrate (CFB) are resistant to acetaminophen (APAP) hepatotoxicity. Whereas the mechanism of protection is not entirely known, CFB decreases protein adducts formed by the reactive metabolite of APAP, N-acetyl-p-benzoquinone imine (NAPQI). NAD(P)H:quinone oxidoreductase 1 (NQO1) is an enzyme with antioxidant properties that is responsible for the reduction of cellular quinones. We hypothesized that CFB increases NQO1 activity, which in turn enhances the conversion of NAPQI back to the parent APAP. This could explain the decreases in APAP covalent binding and glutathione depletion produced by CFB without affecting APAP bioactivation to NAPQI. Administration of CFB (500 mg/kg, i.p.) to male CD-1 mice for 5 or 10 days increased NQO1 protein and activity levels. To evaluate the capacity of NQO1 to reduce NAPQI back to APAP, we utilized a microsomal activating system. Cytochrome P450 enzymes present in microsomes bioactivate APAP to NAPQI, which binds the electrophile trapping agent, N-acetyl cysteine (NAC). We analyzed the formation of APAP-NAC metabolite in the presence of human recombinant NQO1. Results indicate that NQO1 is capable of reducing NAPQI. The capacity of NQO1 to amelioriate APAP toxicity was then evaluated in primary hepatocytes. Primary hepatocytes isolated from mice dosed with CFB are resistant to APAP toxicity. These hepatocytes were also exposed to ES936, a high affinity, irreversible inhibitor of NQO1 in the presence of APAP. Concentrations of ES936 that resulted in over 94% inhibition of NQO1 activity did not increase the susceptibility of hepatocytes from CFB treated mice to APAP. Whereas NQO1 is mechanistically capable of reducing NAPQI, CFB-mediated hepatoprotection does not appear to be dependent upon enhanced expression of NQO1.

Use of the prophylactic amiodarone regimens from the AFIST trials reduced LOS by 3.0 days and frequency of POAF by 22.7%.

At half the recommended single dose, Metabolife Ephedra Free does not affect the QTc interval or other ECG variables over 5 hours. Dose-response studies and studies of longer duration should be conducted.