Joselyn Rojas

C-Reactive Protein: Clinical and Epidemiological Perspectives

An important etiopathogenic component of cardiovascular disease is atherosclerosis, with inflammation being an essential event in the pathophysiology of all clinical pictures it comprises. In recent years, several molecules implicated in this process have been studied in order to assess cardiovascular risk in both primary and secondary prevention. C-reactive protein is a plasmatic protein of the pentraxin family and an acute phase reactant, very useful as a general inflammation marker. Currently, it is one of the most profoundly researched molecules in the cardiovascular field, yet its clinical applicability regarding cardiovascular risk remains an object of discussion, considered by some as a simple marker and by others as a true risk factor. In this sense, numerous studies propose its utilization as a predictor of cardiovascular risk through the use of high-sensitivity quantification methods for the detection of values <1 mg/L, following strict international guidelines. Increasing interest in these clinical findings has led to the creation of modified score systems including C-reactive protein concentrations, in order to enhance risk scores commonly used in clinical practice and offer improved care to patients with cardiovascular disease, which remains the first cause of mortality at the worldwide, national, and regional scenarios.

Polycystic Ovary Syndrome, Insulin Resistance, and Obesity: Navigating the Pathophysiologic Labyrinth

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR), and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome.

Ppar-γ Agonists and Their Role in Type 2 Diabetes Mellitus Management

Type 2 diabetes mellitus and obesity are the most frequent endocrine-metabolic diseases in the world and their pathogenic basis are characterized by insulin resistance and insulin secretion defects that can be demonstrated through several alterations in carbohydrates, lipids, and protein metabolism. The peroxisome proliferator-activated receptors have been identified as key regulators of glucose and lipid metabolism, because they act as transcription factors that stimulate protein synthesis in a wide variety of processes (energetic metabolism, proliferation, and cellular differentiation), of which have been identified 3 types (α, β/δ, γ). The thiazolidenediones are compounds that act as agonists of the peroxisome proliferator-activated receptor-γ increasing the tissues sensibility (muscle, adiposity tissue, and liver) to the insulin action; that is why they are used nowadays in treatment of type 2 diabetes mellitus. These drugs produce several of adverse effects, such as weight increased, edema, anemia, pulmonary edema, and congestive cardiac failure. Even their use have been related for some studies to an increased in the myocardium infarct risk; this correlation has not been a strong determinant to remove them from the market.

AMPK as Target for Intervention in Childhood and Adolescent Obesity.

Childhood obesity is a major worldwide health problem. Intervention programs to ameliorate the rate of obesity have been designed and implemented; yet the epidemic has no end near in sight. AMP-activated protein kinase (AMPK) has become one of the most important key elements in energy control, appetite regulation, myogenesis, adipocyte differentiation, and cellular stress management. Obesity is a multifactorial disease, which has a very strong genetic component, especially epigenetic factors. The intrauterine milieu has a determinant impact on adult life, since the measures taken for survival are kept throughout life thanks to epigenetic modification. Nutrigenomics studies the influence of certain food molecules on the metabolome profile, raising the question of an individualized obesity therapy according to metabolic (and probably) genetic features. Metformin, an insulin sensitizing agent, its known to lower insulin resistance and enhance metabolic profile, with an additional weight reduction capacity, via activation of AMPK. Exercise is coadjutant for lifestyle modifications, which also activates AMPK in several ways contributing to glucose and fat oxidation. The following review examines AMPKs role in obesity, applying its use as a tool for childhood and adolescent obesity.

Epicardial Fat: Physiological, Pathological, and Therapeutic Implications

Epicardial fat is closely related to blood supply vessels, both anatomically and functionally, which is why any change in this adipose tissues behavior is considered a potential risk factor for cardiovascular disease development. When proinflammatory adipokines are released from the epicardial fat, this can lead to a decrease in insulin sensitivity, low adiponectin production, and an increased proliferation of vascular smooth muscle cells. These adipokines move from one compartment to another by either transcellular passing or diffusion, thus having the ability to regulate cardiac muscle activity, a phenomenon called vasocrine regulation. The participation of these adipokines generates a state of persistent vasoconstriction, increased stiffness, and weakening of the coronary wall, consequently contributing to the formation of atherosclerotic plaques. Therefore, epicardial adipose tissue thickening should be considered a risk factor in the development of cardiovascular disease, a potential therapeutic target for cardiovascular pathology and a molecular point of contact for “endocrine-cardiology.”

Sensitivity and Specificity Improvement in Abdominal Obesity Diagnosis Using Cluster Analysis during Waist Circumference Cut-Off Point Selection

Introduction. The purpose of this study was to analyze the influence of metabolic phenotypes during the construction of ROC curves for waist circumference (WC) cutpoint selection. Materials and Methods. A total of 1,902 subjects of both genders were selected from the Maracaibo City Metabolic Syndrome Prevalence Study database. Two-Step Cluster Analysis (TSCA) was applied to select metabolically healthy and sick men and women. ROC curves were constructed to determine WC cutoff points by gender. Results. Through TSCA, metabolic phenotype predictive variables were selected: HOMA2-IR and HOMA2-βcell for women and HOMA2-IR, HOMA2-βcell, and TAG for men. Subjects were classified as healthy normal weight, metabolically obese normal weight, healthy and metabolically disturbed overweight, and healthy and metabolically disturbed obese. Final WC cutpoints were 91.50 cm for women (93.4% sensitivity, 93.7% specificity) and 98.15 cm for men (96% sensitivity, 99.5% specificity). Conclusions. TSCA in the selection of the groups used in ROC curves construction proved to be an important tool, aiding in the detection of MOWN and MHO which cannot be identified with WC alone. The resulting WC cutpoints were <91.00 cm for women and <98.00 cm for men. Furthermore, anthropometry is insufficient to determine healthiness, and, biochemical analysis is needed to properly filter subjects during classification.

Glucosamine for osteoarthritis: biological effects, clinical efficacy, and safety on glucose metabolism.

Osteoarthritis is a chronic degenerative disorder that currently represents one of the main causes of disability within the elderly population and an important presenting complaint overall. The pathophysiologic basis of osteoarthritis entails a complex group of interactions among biochemical and mechanical factors that have been better characterized in light of a recent spike in research on the subject. This has led to an ongoing search for ideal therapeutic management schemes for these patients, where glucosamine is one of the most frequently used alternatives worldwide due to their chondroprotective properties and their long-term effects. Its use in the treatment of osteoarthritis is well established; yet despite being considered effective by many research groups, controversy surrounds their true effectiveness. This situation stems from several methodological aspects which hinder appropriate data analysis and comparison in this context, particularly regarding objectives and target variables. Similar difficulties surround the assessment of the potential ability of glucosamine formulations to alter glucose metabolism. Nevertheless, evidence supporting diabetogenesis by glucosamine remains scarce in humans, and to date, this association should be considered only a theoretical possibility.

Single-nucleotide polymorphisms in adiponectin, AdipoR1, and AdipoR2 genes: insulin resistance and type 2 diabetes mellitus candidate genes.

It has already been a decade and a half since the discovery of adiponectin and its role as an insulin sensitizer and only 7 years since its receptors, AdipoR1 and AdipoR2, were described. A single-nucleotide polymorphism (SNP) is a DNA sequence variation that affects only one nucleotide; it may vary from one population to another with different predisposing factors to diseases and other ailments. Once some of the effects of adiponectin and its receptors were known, it was not long until an effort was made to find the associations between specific SNPs of the genes of this hormone and its receptors as genetic risk factors for insulin resistance, type 2 diabetes mellitus, and metabolic syndrome, although these genes were investigated as possible candidates related to the development of these metabolic disorders. All of these possible associations were studied in different populations from France, Finland, the United Kingdom, North America, and Japan, showing hardly concluding results, and because of that it is highly controversial to directly associate one of the genes mentioned above to insulin resistance, type 2 diabetes mellitus, and metabolic syndrome. All of these inconsistencies lead to a review that summarizes the SNPs of the genes of adiponectin, AdipoR1, and AdipoR2 that are mostly related to insulin resistance syndrome, type 2 diabetes mellitus, and metabolic syndrome, although presenting the possible factors that should be taken into account to homogenize the results obtained until now.

Epidemiologic Behavior of Obesity in the Maracaibo City Metabolic Syndrome Prevalence Study

Introduction Obesity is a worldwide public health issue. Since the epidemiological behaviour of this disease is not well established in our country, the purpose of this study was to determinate its prevalence in the Maracaibo City, Zulia State- Venezuela. Materials and Methods A cross-sectional study was undertaken using the data set from the Maracaibo City Metabolic Syndrome Prevalence Study. The sample consists of 2108 individuals from both genders and randomly selected: 1119 (53.09%) women and 989 (46.91%) men. The participants were interrogated for a complete clinical history and anthropometric measurements. To classify obesity, the WHO criteria for Body Mass Index (BMI), and Waist Circumference (WC) from the IDF/NHLBI/AHA/WHF/IAS/IASO-2009 (IDF-2009) and ATPIII statements were applied. Results For BMI, obesity had an overall prevalence of 33.3% (n = 701), and according to gender women had 32.4% (n = 363) and men had 34.2% (n = 338). Overweight had a prevalence of 34.8% (n = 733), Normal weight had 29.8% (n = 629), and Underweight had 2.1% (n = 45). Adding Obesity and Overweight results, the prevalence of elevated BMI (>25 Kg/m2) was 68.1%. Using the IDF-2009 WCs cut-off, Obesity had 74.2% prevalence, compared to 51.7% using the ATPIII parameters. Conclusions These results show a high prevalence of abdominal obesity in our locality defined by the WHO, IDF-2009 and ATPIII criteria, which were not designed for Latin-American populations. We suggest further investigation to estimate the proper values according to ethnicity, genetic background and sociocultural aspects.

International physical activity questionnaire overestimation is ameliorated by individual analysis of the scores.

Sedentarism is considered a risk factor for coronary heart disease and death from any cardiovascular disease. The International Physical Activity Questionnaire (IPAQ) assesses physical activity in metabolic equivalents, using 4 dimensions: occupation, transportation, household activities, and leisure-time physical activity. The purpose of this investigation was to assess physical activity levels in the patients enrolled in the Maracaibo City Metabolic Syndrome Prevalence Study, currently undertaken by the “Dr. Félix Gómez” Endocrine-Metabolic Research Center. Two thousand one hundred eight individuals were recruited and subjected to a standard Medical chart, Graffar scale, and IPAQ long form, applied by trained personnel. Description of the population was done using mean, SD, and coefficient of variation. IPAQ scores were analyzed as medians and distributed by percentiles. From the 2108 individuals, 46.9% were men and 53.1% were women. The most prevalent physical activity was high physical activity with 39.9%, followed by moderate physical activity with 36.9% and low physical activity with 23.2%. Medians for each IPAQ dominion were occupation with 0.00 (0.00–66.00), transportation with 165.00 (0.00–463.00), household activities with 772.50 (0.00–2520.00), and leisure time with 0.00 (0.00–594.00). Using leisure-time scores, a new reclassification was conducted, obtaining 1245 subjects with 0 metabolic equivalents in this dominion. From this new subsample, 43.6% had High physical activity, 56.95% had Moderate physical activity, and 91% had Low physical activity, demonstrating an important overestimation in the former sample results. IPAQ overestimates moderate and vigorous activity in the adult population of the Maracaibo Municipality. Overestimation is mainly located in the household- and gardening-related activity.