Endothelial dysfunction symbolizes several pathological conditions, including altered anticoagulant and anti-inflammatory properties of the endothelium, impaired modulation of vascular growth, and dysregulation of vascular remodeling. Nevertheless, this term has been used commonly to refer to an impairment of endothelium-dependent vasorelaxation caused by a loss of nitric oxide bioactivity. The clinical and scientific relevance of nitric oxide synthesis and bioavailability in endothelial dysfunction is based on the fact that it is a common factor in the pathogenesis of cardiovascular diseases. These alterations have been demonstrated in both animal models and humans, in the scope of dangerous pathological conditions such as cigarette smoking, hypertension, hypercholesterolemia, aging, diabetes, and heart failure. A decline in nitric oxide bioavailability may be caused by decreased expression of the endothelial nitric oxide synthase, a reduction of substrate or cofactors for this enzyme, alterations of cellular signaling, enzyme inhibition by asymmetric dimethyl arginine, and, finally, accelerated nitric oxide degradation by reactive oxygen species. The knowledge of the processes related to these alterations becomes of remarkable importance for understanding the generation of innovative and effective therapeutic strategies for cardiovascular diseases.

Type 2 diabetes mellitus is a metabolic disorder that results from defects in both insulin secretion and insulin action. Questions remain about when insulin therapy is indicated; thus, the aim of this study was to evaluate homeostasis model assessment beta-cell (HOMAbetacell) values as surrogate criteria for insulin therapy indication in patients with type 2 diabetes. A prospective study was performed involving 189 type 2 diabetic patients with deficient metabolic control assessed by clinical and laboratory parameters. All patients received nutritional intervention and combination therapy with metformin and glimepiride. Patients who did not respond were admitted to the next phase, which consisted of glimepiride + metformin + rosiglitazone oral therapy and revaluation after 3 months. Comparisons between responders and nonresponders in this phase were made in order to achieve differences in metabolic parameters and beta cell function. Of 189 patients studied, 150 (79.36%) were considered full responders in the first phase of this study. The remaining 39 patients were admitted in the second trial phase, in which 20 patients (51.28%) responded to triple oral therapy, while the other 19 (49.72%) required insulin therapy. Significant differences were found in fasting and postprandial glycemia (P < 0.001; P < 0.004) between the non-insulin-requiring group (200 +/- 12.0 mg/dL; 266.05 +/- 17,67 mg/dL) and the insulin-requiring group (291.5 +/- 17.6 mg/dL; 361.6 +/- 26.1 mg/dL). Likewise, significant differences were observed in homeostasis model assessment insulin resistance (HOMAIR) and HOMAbetacell values (P < 0.002; P < 0.04) between non-insulin-requiring patients (7.7 +/- 0.8; 24.5 +/- 1.3%) and insulin-requiring patients (12.6 +/- 1.2; 19.4 +/- 2.4%). Finally, significant differences were observed when comparing body mass index (non-insulin-requiring group, 29.2 +/- 0.4 kg/m, versus insulin-requiring group, 27.1 +/- 0.9 kg/m; P < 0.05). HOMAbetacell determination in clinical practice is a useful tool to determine when insulin therapy should be started for type 2 diabetic patients.

High-density lipoprotein (HDL) cholesterol is a heterogeneous group of lipoproteins exhibiting a variety of properties like prostacyclin production stimulation, decrease in platelet aggregation, endothelial cell apoptosis inhibition, and low-density lipoprotein oxidation blockade. Epidemiologic studies have shown an inverse relation between HDL cholesterol levels and cardiovascular risk. Low HDL cholesterol is associated with increased risk for myocardial infarction, stroke, sudden death, peripheral artery disease, and postangioplasty restenosis. In contrast, high HDL levels are associated with longevity and protection against atherosclerotic disease development. Given the evolving epidemic of obesity, diabetes mellitus, and metabolic syndrome, the prevalence of low HDL will continue to rise. In the United States, low HDL is present in 35% of men, 15% of women, and approximately 63% of patients with coronary artery disease. Data extracted from the Framingham study highlight that 1-mg increase in HDL levels decreases by 2% to 3% the risk of cardiovascular disease. There is no doubt regarding clinical importance about isolated low HDL, but relatively few clinicians consider a direct therapeutic intervention of this dyslipidemia. In this sense, lifestyle measures should be the first-line strategy to manage low HDL levels. On the other hand, pharmacologic options include niacin, fibrates, and statins. Fibrates appear to reduce risk preferentially in patients with low HDL with metabolic syndrome, whereas statins reduce risk across all levels of HDL. Torcetrapib, a cholesteryl esters transfer protein inhibitor, represented a hope to raise this lipoprotein; however, all clinical trials on this drug had ceased after ILLUMINATE, RADIANCE and ERASE trials had recorded an increase in mortality, rates of myocardial infarction, angina, and heart failure. In the near future, drugs as beta-glucans, Apo-A1 mimetic peptides, and ACAT inhibitors, are the new promises to treat this condition.

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