Raquel Cano

Effect of Cigarette Smoking on the Oxidant/ Antioxidant Balance in Healthy Subjects

Background and Purpose:Cigarette smoking has been associated with the development of cardiovascular disease and cancer. Even though the molecular mechanism(s) are not clear, the pathology has been related to oxygen free radicals present in cigarette smoke. Thus, the main objective of this study was to establish the changes in the oxidation/antioxidation balance induced by cigarette smoking. Methods:Thirty healthy subjects (15 smokers and 15 nonsmokers) of both sexes were studied. The smokers group had smoked a mean of 14 cigarettes per day for an average of 4.5 years. Fasting serum levels of malondialdehyde (MDA), a marker of oxidative stress, nitric oxide (NO), reduced glutathione (GSH), and vitamin C (ascorbic and dehydroascorbic acids) were measured. Results:Fasting NO concentration was significantly higher in smokers (51.3 ± 5.3 μM) than in nonsmokers (35.2 ± 4.8 μM, P < 0.05). The smokers had significantly higher serum dehydroascorbic acid levels (2.4 ± 0.5 mg/dL, P < 0.03) than the nonsmokers (1.08 ± 0.08 mg/dL). No significant differences were observed in the levels of ascorbic acid, MDA, and GSH between the smokers and nonsmokers. Conclusions:Our results suggest that exposure to cigarette smoke increases NO synthesis, such that NO may act in a compensatory way as an inhibitor of lipid peroxidation. Smoking also activates other antioxidative mechanisms such as involving vitamin C. These protective mechanisms appear to be enough in preventing accumulation of oxidative products such as MDA and avoiding oxidative damage.

The Maracaibo city metabolic syndrome prevalence study: design and scope.

The metabolic syndrome (MS) is a conglomerate of interrelated risk factors-including obesity, atherogenic dyslipidemia, arterial hypertension, and insulin resistance-which exponentially increase the risk of developing cardiovascular disease and type 2 diabetes mellitus. The purpose of this study was to determine the prevalence of MS according to the criteria published by the International Diabetes Federation, in individuals of both sexes over 18 years of age. This is a cross-sectional study based on MS prevalence in a representative sample from the Maracaibo district, Zulia State. The population of Maracaibo, according to the last census in 2001, was 1,219,927 habitants, with a 2007 population estimation of 1,428,043 habitants according to the National Institute of Statistics (NIS). Likewise, NIS projects that for the year 2009, 59.7% of the population of Venezuela will have individuals over 18 years of age. Using these data, the sample for Maracaibo District corresponds to 1986 individuals with or above 18 years of age. The data recollection was conducted by health professionals and medicine students, previously trained. The participants were subject to inquiry previous written consent and a medical examination, and qualitative variables such as smoking habit, socioeconomic status, physical activity, race, alcoholism, and nutritional habits, and quantitative ones like blood pressure, anthropometry, and blood works were determined. There is clear evidence that there is a lack of research and validated values to use as reference in our country and maybe in Latin America. Taking into account all that has been exposed here, this study will serve as a pilot for the numerous statistical determinations that will soon come afterward, providing first-hand accurate evidence on the behavior of the MS in the Latin American populace.

Lipoprotein(a): from molecules to therapeutics.

Lipoprotein (a) [Lp(a)] was discovered by Kare Berg in 1963 from the study of low-density lipoprotein genetic variants. Lp(a) contains a unique protein, apolipoprotein(a), which is linked to the Apo B-100 through a disulfide bond that gives it a great structural homology with plasminogen, and confers it atherogenic and atherothrombotic properties. Interest in Lp(a) has increased because an important association between high plasma levels of Lp(a) and coronary artery disease and cerebral vascular disorders has been demonstrated. Numerous case control studies have confirmed that hyper-Lp(a) is a risk factor for premature cardiovascular disease. Lp(a) is identified as a genetic trait with autosomal transmission, codified by one of the most studied polymorphic genes in humans. It has been demonstrated that variations in this gene are a major factor in the serum levels of Lp(a). Variations differ considerably between individuals and sex across populations. Various approaches to drug treatment using fibric acid derivatives, growth hormone, insulin-like growth factor-1, alcohol extracted soy protein, niacin, and exercise have been proven to decrease Lp(a) in high risk patients, but none has really been an effective therapeutic option for successfully reducing Lp(a) plasma levels.

Homeostasis Model Assessment (HOMA) as Surrogate Insulinization Criteria in Patients With Type 2 Diabetes

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 β-cell (HOMAβcell) 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 β 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 HOMAβcell 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/m2, versus insulin-requiring group, 27.1 ± 0.9 kg/m2; P < 0.05). HOMAβcell determination in clinical practice is a useful tool to determine when insulin therapy should be started for type 2 diabetic patients.

Metformin plus low-dose glimeperide significantly improves Homeostasis Model Assessment for insulin resistance (HOMA(IR)) and beta-cell function (HOMA(beta-cell)) without hyperinsulinemia in patients with type 2 diabetes mellitus.

Objective:Type 2 diabetes mellitus is characterized by insulin resistance and defects in insulin secretion from pancreatic β-cells, which have been studied by using euglycemic/hyperinsulinemic clamps. However, it is difficult to study insulin resistance and β-cell failure by these techniques in humans. Therefore, the aim of this study was to evaluate the effect of three different antidiabetic therapeutic regimens on insulin resistance and β-cell activity by using a mathematical model, Homeostasis Model Assessment for insulin resistance (HOMAIR) and β-cell function (HOMAβ-cell). Research design and methods:Seventy type 2 diabetic patients were randomly assigned to one of three therapeutic regimens: (A) metformin + American Diabetic Association (ADA)-recommended diet + physical activity; (B) metformin + low-dose glimepiride + ADA diet + physical activity; or (C) ADA diet + physical activity (no drugs). Blood samples were obtained before and after the treatment to determine serum levels of fasting and post-prandial blood glucose, fasting insulin, and glycosylated hemoglobin (HbA1c), and HOMAIR and HOMAβ-cell were calculated. Results:Fasting and post-prandial levels of glucose, HbA1c, and fasting insulin and calculated HOMAIR and HOMAβ-cell values before treatment were significantly higher than the respective values after treatment for all groups of patients (P < 0.01). Significant differences were also found when comparing the treatment-induced reduction in fasting blood glucose (51.8%; P < 0.01), post-prandial blood glucose (55.0%; P < 0.05), and HOMAIR (65.3%; P < 0.01) in patients of Group B with that in patients receiving other therapeutic options (Groups A and C). Conclusions:Metformin plus low-dose glimepiride (plus ADA diet and physical activity) is a more effective treatment for type 2 diabetes than either metformin plus ADA diet and physical activity or ADA diet and physical activity alone. Determination of HOMAIR and HOMAβ-cell values is an inexpensive, reliable, less invasive, and less labor-intensive method than other tests to estimate insulin resistance and β-cell function in patients with type 2 diabetes mellitus.

Effect of drugs interacting with the dopaminergic receptors on glucose levels and insulin release in healthy and type 2 diabetic subjects.

Dopamine agonists play an important role in the regulation of the central nervous-cardiovascular, renal, and hormonal systems through stimulation of dopaminergic (DA1 and DA2) and α- and β-adrenergic receptors. Several studies have shown that in fat and diabetic mice. The aim of the present study was to evaluate the interaction of the dopaminergic and endocrine systems by determining the effect of the dopaminergic antagonist, metoclopramide, and dopamine on insulin secretion and cardiovascular response by blockade and activation of dopamine receptors in healthy and type 2 diabetic subjects. Healthy subjects (n =15) and subjects with type 2 diabetes (n = 15) of both genders, aged 18 to 60 years, were recruited into this study. A comparative experimental design of 90 minutes was performed in which placebo (0.9% saline) was infused intravenously for the first 30 minutes followed by metoclopramide (7.5 μg/kg/min), a dopamine receptor antagonist for 30 minutes, and then metoclopramide (7.5 μg/kg/min) plus dopamine (0.5-3 μg/kg/min) for 30 minutes. The following clinical and biochemical parameters were measured at the beginning and then every 30 minutes of the experimental period (30′, 60′ and 90′): systolic-diastolic and mean arterial blood pressure, heart rate, serum glucose, insulin, triacylglycerides, and total cholesterol. Baseline glycosylated hemoglobin was measured and homeostasis model assessment for insulin resistance was calculated from insulin and glucose levels. Twelve-lead electrocardiograms were also obtained at these points. Dopamine infusion induced an increase in serum insulin, systolic blood pressure, and heart rate in healthy subjects but not in subjects with type 2 diabetes. Infusion of metoclopramide induced a hypotensive effect in healthy subjects, which was blunted by inclusion of dopamine in the infusion mixture. In subjects with diabetes, metoclopramide had no effect on blood pressure, but addition of dopamine raised systolic blood pressure. Neither metoclopramide nor dopamine altered significantly the lipid profile in healthy or diabetic subjects. Dopaminergic drugs increase serum insulin probably by interacting with dopaminergic receptors, but stimulation of β-adrenergic receptors cannot be ruled out. Stimulation of cardiovascular dopamine receptors also caused modifications of hemodynamic parameters in healthy subjects, but apparently these receptors are attenuated in patients with type 2 diabetes probably as a result of endothelial dysfunction and alterations in the sympathetic nervous system sensitivity.

Pharmacologic Management of Isolated Low High-Density Lipoprotein Syndrome

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 β-glucans, Apo-A1 mimetic peptides, and ACAT inhibitors, are the new promises to treat this condition.

Variations of lipoprotein(a) levels in the metabolic syndrome: a report from the Maracaibo City Metabolic Syndrome Prevalence Study.

Background. Lipoprotein(a) [Lp(a)] is a known risk factor for cardiovascular disease, yet its influence on metabolic syndrome (MS) is still controversial. The purpose of this study was to assess the impact generated by this diagnosis in serum Lp(a) concentrations. Materials and Methods. A total of 1807 subjects of both genders (55.3% women and 44.7% men) belonging to the Maracaibo City Metabolic Syndrome Prevalence Study were evaluated. Results were expressed as Mean ± SD, determining differences through Students t-test and One-Way ANOVA test. Multiple logistic regression models were utilized for analyzing factors associated with elevated serum Lp(a) levels and MS. Total cholesterol and LDL-C were corrected according to Lp(a)-Cholesterol when necessary. Results. No differences were found in Lp(a) values between genders; P = 0,292. The association between MS and the classification of Lp(a) was statistically significant (χ 2 = 28.33; P < 0,0001), with greater levels in subjects with this diagnosis. In the univariate analysis, subjects with each of the separate diagnostic criteria showed higher serum Lp(a) concentrations, except for hyperglycemia. Conclusions. Lp(a) values exhibit important variations regarding MS and each of its components. Impaired fasting glucose appeared as a protecting factor against elevated Lp(a) concentrations, whereas its association with LDL-C and hs-CRP suggests a potential pro-inflammatory role.

Effects of Metoclopramide and Metoclopramide/ Dopamine on Blood Pressure and Insulin Release in Normotensive, Hypertensive, and Type 2 Diabetic Subjects

The objective is to determine cardiovascular and insulin release effects under metoclopramide (MTC) and dopamine (DA) infusion by using an acute comparative design with the intravenous infusion of both drugs. We evaluated 15 normal (normotensive and normoglycemic) subjects, 13 hypertensive, and 15 type 2 diabetic subjects. Subjects were submitted to an experimental design in which we first gave them a 0.9% saline solution for 30 minutes, and then administered MTC at 7.5 μg kg−1 min−1 through an intravenous infusion during a period of 30 minutes. Although subjects were receiving MTC, we added an intravenous infusion of DA at 1-3 μg kg−1 min−1 during 30 minutes. Blood pressure, heart rate, serum lipid profile, and insulin levels were measured. Sympathetic reactivity by the cold pressor test was also measured. In normotensive subjects, there was a systolic blood pressure and heart rate increase during MTC plus DA infusion. In subjects with diabetes mellitus there was a heart rate increase without changes in blood pressure during the MTC plus DA infusion period. In hypertensive subjects, MTC induced a significant decrease of systolic and diastolic blood pressure. During MTC plus DA period there was an increase of heart rate but no significant changes in blood pressure. During cold pressor test in both diabetic and hypertensive subjects, there were significant increases of both blood pressure and heart rate. Insulin serum levels increased in normotensive and hypertensive subjects but were attenuated in subjects with diabetes mellitus. We conclude that there is a pharmacologic interaction between MTC and DA, that the pressor effects of DA are due to activation to beta and alpha adrenergic receptors, and that the cardiovascular effects of DA in type 2 diabetic subjects are attenuated by a probable defect in sympathetic system and to endothelial dysfunction.

The Sick Adipocyte Theory: The Forces of Clustering at Glance

The concept and repercussions of Obesity have evolved alongside Humankind. First seen as an advantageous trait in the beginning of time, it s now a double edged sword definition that shows how slowly genometabolic traits are acquired and how quickly can environmental factors turn it around. Being obese is not only a matter of Body Mass Index (BMI) and adiposity, its influence stretches out to include type 2 Diabetes Mellitus (T2DM), Psychological disorders like depression, anxiety disorders, and other eating disorders, Osteoarticular problems, Metabolic Syndrome, Cardiovascular Diseases (CVD) like hypertension, stroke, and myocardial infarction, Neurological disorders, Cancer, and even Immunity-related issues, such as low grade inflammation (Must, 1999; Oster, 2000; Thompson, 2001; Marchesini, 2003; Adami, 2003; Niskanen, 2004; Panagiotakos, 2005). Obesity has been rising slowly yet steadily ever since the Industrial revolution and its pace has increased since the dawn of the 20th Century. Even though nutritional disorders have plagued Man, it was common to see that undernutrition and malnourishment were the higher numbers around the globe. Yet, the tables were turned when Gardner & Halweil published in 2000 that the number of excess-weight patients surpassed the number of the underweight population, welcoming Humanity to the supersized phase of the land of milk and honey (O Dea, 1992). In 2006, the World Health Organization reported that by 2005 1.6 billion above 15 years of age would be overweight and at least 400 million would be obese, while it is predicted to reach 2.3 billion of overweight and over 700 million of obese adults by the year 2015 (World Health Organization [WHO], 2006). The figures published by Kelly et al, 2008 darken the scope, predicting that by 2030 1.12 billion individuals will be obese and 2.16 million will be overweight. There are many factors that have influenced the increasing prevalence of obesity worldwide, and have influenced the scientific community to coin the term obesogenic environment (Egger & Swinbum, 1997) as the external factors that act as “second hit” triggers in the