Ali Jawa

Beta-blockers have a beneficial effect upon endothelial function and microalbuminuria in African-American subjects with diabetes and hypertension

BACKGROUNDnType 2 diabetes mellitus (T2DM) with microalbuminuria (MA) is associated with increased risk of cardiovascular events (CVE) that may be attenuated by angiotensin-converting enzyme inhibitors (ACEIs), unless microalbuminuria persists (PMA). African-Americans (AA) have a higher prevalence of nephropathy with suboptimal response to ACEIs. We studied the effects of beta-blockers addition and comparative effects of carvedilol with metoprolol on 24-h urinary-albumin excretion (UAE) and endothelial function (EF) in AA with PMA.nnnMETHODSnThirty-four AA 30-70 years of age with T2DM and PMA despite ACEI therapy were randomized to receive carvedilol or metoprolol in addition to ACEI and any other concurrent therapy. Carvedilol/metoprolol dose was titrated to achieve blood pressure (BP) <130/80 mm Hg. UAE and brachial-artery reactivity were studied at baseline and 12 weeks. We analyzed the effects of addition of beta-blockers and whether there was any difference in response between the two beta-blockers.nnnRESULTSnThirty-three subjects completed the study; BP decreased to <135/80 mm Hg. After 12 weeks, beta-blocker treatment resulted in significant increase in flow-mediated dilatation (FMD) from 3.5+/-1% to 8.5+/-1% (P=.004) and significant reduction in mean log-transformed UAE from 2.655 g/g Cr+/-0.087 to 2.533 g/g Cr+/-0.093 (P=.028). FMD increased by 240% (P=.033) with carvedilol and by 110% (P=.096; NS) with metoprolol. UAE decreased with carvedilol by 0.35 g/g Cr (P=.023) and with metoprolol by 0.23 g/g Cr (P=.298; NS).nnnCONCLUSIONnOur results clearly indicate that addition of beta-blockers to ACEI improves EF and reduces UAE in high-risk AA T2DM patients with PMA. Carvedilol but not metoprolol improves EF and reduces UAE in AA with identical BP control. Larger trials are needed to further elucidate the differential effects of carvedilol/metoprolol on EF and UAE and its impact on CVE in such patients.

Effects of peptides, with emphasis on feeding, pain, and behavior: A 5-year (1999–2003) review of publications in Peptides

Novel effects of naturally occurring peptides are continuing to be discovered, and their mechanisms of actions as well as interactions with other substances, organs, and systems have been elucidated. Synthetic analogs may have actions similar or antagonistic to the endogenous peptides, and both the native peptides and analogs have potential as drugs or drug targets. The journal Peptides publishes many leading articles on the structure-activity relationship of peptides as well as outstanding reviews on some families of peptides. Complementary to the reviews, here we extract information from the original papers published during the past five years in Peptides (1999-2003) to summarize the effects of different classes of peptides, their modulation by other chemicals and various pathophysiological states, and the mechanisms by which the effects are exerted. Special attention is given to peptides related to feeding, pain, and other behaviors. By presenting in condensed form the effects of peptides which are essential for systems biology, we hope that this summary of existing knowledge will encourage additional novel research to be presented in Peptides.

Pioglitazone Restores Endothelial Function in Patients with Type 2 Diabetes Treated with Insulin

The primary aim of this study was to evaluate the effect of pioglitazone on endothelial function, as assessed by flow-mediated dilatation (FMD) nitroglycerine-induced dilatation (NID) in patients with type 2 diabetes mellitus treated with insulin. A randomized double-blind placebo-controlled trial involved 20 patients with insulin-treated type 2 diabetes. Patients received either pioglitazone 30 mg or placebo for 4 months. FMD, NID, and HbA1c were measured before and after 4 months of treatment. HbA1c decreased from 10.0 (+/- 2.3) to 8.4 (+/- 2.0) in the pioglitazone group, a statistically significant improvement in glycemic control (p = 0.018). HbA1c was unchanged in the placebo group (p = 0.477). Endothelial function as assessed by FMD significantly improved from 10.1 (+/- 4.0)% to 14.6 (+/- 6.2)% in the pioglitazone group (p = 0.036) as compared to the placebo group (p = 0.705). There was a trend towards improvement in the NID in the pioglitazone group (from 13.3 +/- 8.0% to 18.9 +/- 5.4%; p = 0.056). In insulin-treated patients with type 2 diabetes, the addition of pioglitazone improves endothelial function, as measured by FMD. Addition of pioglitazone to insulin in type 2 diabetes patients may favorably impact vascular function in diabetes, even after many years of insulin resistance and hyperglycemia.

Intensive Treatment and Complications of Diabetes

Diabetes mellitus (DM) is a growing health problem in the USA, afflicting over 18.2 million Americans. Morbidity and mortality from DM most commonly result from the long-term complications of the disease. “Intensive therapy” reduces blood sugars to near normal and effective management of other associated risk factors such as lipid abnormalities and blood pressure (BP). New clinical trials are being carried out to determine whether goals for intensive therapy should be lower than current goals and to test various therapeutic strategies to determine the optimum methods to prevent diabetes complications. Cardiovascular disease (CVD) disproportionately affects people with diabetes and is a leading cause of death. So far, intensive glycemic control has not been conclusively shown to decrease cardiovascular events. The therapeutic agents used in treating glycemia have different effects on cardiovascular risks and therefore may have different effects on outcome. Metformin was the only oral anti-diabetic medication shown to decrease cardiovascular events independent of glycemic control. Thiazolidinediones improve insulin resistance and lower insulin concentrations, which may be beneficial because hyperinsulinemia is an independent predictor of CVD. In the recent PROACTIVE study, a pioglitazone treatment was associated with a significant reduction in myocardial infarction and cardiovascular mortality, although that was not the primary endpoint of the study. Insulin therapy acutely reduces mortality and morbidity in patients with hyperglycemia when critically ill, but the effect on cardiovascular events is unclear. In contrast, insulin secretagogues have very little effect on both cardiovascular risk factors and outcomes. Thus, the role of intensive glycemic control and the choice of therapeutic agents to reduce the macrovascular complications of diabetes are unclear.