María Calvo

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.

Prevalence and Associated Factors of Insulin Resistance in Adults from Maracaibo City, Venezuela

Background and Aim. Insulin resistance (IR) is a prominent pathophysiologic component in a myriad of metabolic disorders, including obesity, prediabetes, and type 2 diabetes mellitus, which are common in our locality. The objective of this study was to determine the prevalence of IR and factors associated with this condition in an adult population from Maracaibo city, Venezuela. Methodology. A cross-sectional, descriptive study with multistaged randomized sampling was carried out in 2026 adults. IR was defined as HOMA2-IR ≥ 2. A multiple logistic regression model was constructed in order to evaluate factors associated with IR. Results. The prevalence of IR was 46.5% (n = 943), with 46.7% (n = 450) in the general population, 46.4% (n = 493) in females, and 47.90% (n = 970) in males (p = 0.895). IR prevalence tended to increase with age and was significantly greater in subjects aged ≥30 years (χ 2 = 16.726; p = 2.33 × 10−4). Employment, alcohol consumption, obesity, high triacylglycerides, low HDL-C, and dysglycemia were associated with greater odds of IR, whereas a high level of physical activity appeared to be weak protective factor against IR. Conclusions. The prevalence of IR is elevated in our locality. The main determinants of this condition appear to be the presence of obesity, high triacylglycerides, low HDL-C, dysglycemia, and alcohol intake.

Physiologic Course of Female Reproductive Function: A Molecular Look into the Prologue of Life.

The genetic, endocrine, and metabolic mechanisms underlying female reproduction are numerous and sophisticated, displaying complex functional evolution throughout a womans lifetime. This vital course may be systematized in three subsequent stages: prenatal development of ovaries and germ cells up until in utero arrest of follicular growth and the ensuing interim suspension of gonadal function; onset of reproductive maturity through puberty, with reinitiation of both gonadal and adrenal activity; and adult functionality of the ovarian cycle which permits ovulation, a key event in female fertility, and dictates concurrent modifications in the endometrium and other ovarian hormone-sensitive tissues. Indeed, the ultimate goal of this physiologic progression is to achieve ovulation and offer an adequate environment for the installation of gestation, the consummation of female fertility. Strict regulation of these processes is important, as disruptions at any point in this evolution may equate a myriad of endocrine-metabolic disturbances for women and adverse consequences on offspring both during pregnancy and postpartum. This review offers a summary of pivotal aspects concerning the physiologic course of female reproductive function.

Prevalence and Risk Factors associated with Impaired Fasting Glucose inAdults from Maracaibo City, Venezuela

Objective: The purpose of this study was to evaluate the prevalence and risk factors associated with impaired fasting glucose (IFG) in adult individuals from Maracaibo city, Venezuela. Materials and methods: 2230 patients from the Maracaibo Metabolic Syndrome Prevalence Study were selected. IFG was defined according to the 2016 ADA criteria. A multiple logistic regression model was constructed in order to assess risk factors associated with IFG. Results: In the general population, the prevalence of IFG was 19.5% (n=435), with 46.4% (n=202) being women and 53.6% (n=233) being men, p=0.004. The main risk factors associated with IFG were age (≥60 years: OR=2.31; CI 95%=1.23-4.35; p<0.01), alcohol consumption, abdominal obesity and insulin resistance. After evaluating individuals with IFG exclusively, the major risk factor was the presence of elevated high-sensitivity C-Reactive Protein levels (OR=2.03; CI 95%=1.13-3.67; p<0.02). Conclusions: In Maracaibo the prevalence of IFG is similar to that of international reports. It is associated with a variety of risk factors, especially abdominal obesity, insulin resistance and low-grade inflammation, demonstrating the close link between adiposopathy and alterations in glucose metabolism.

Optimal cutoff for the evaluation of insulin resistance through triglyceride-glucose index: A cross-sectional study in a Venezuelan population

Background: Insulin resistance (IR) evaluation is a fundamental goal in clinical and epidemiological research. However, the most widely used methods are difficult to apply to populations with low incomes. The triglyceride-glucose index (TGI) emerges as an alternative to use in daily clinical practice. Therefore the objective of this study was to determine an optimal cutoff point for the TGI in an adult population from Maracaibo, Venezuela. Methods: This is a sub-study of Maracaibo City Metabolic Syndrome Prevalence Study, a descriptive, cross-sectional study with random and multi-stage sampling. For this analysis, 2004 individuals of both genders ≥18 years old with basal insulin determination and triglycerides < 500 mg/dl were evaluated.. A reference population was selected according to clinical and metabolic criteria to plot ROC Curves specific for gender and age groups to determine the optimal cutoff point according to sensitivity and specificity.The TGI was calculated according to the equation: ln [Fasting triglyceride (mg / dl) x Fasting glucose (mg / dl)] / 2. Results: The TGI in the general population was 4.6±0.3 (male: 4.66±0.34 vs. female: 4.56±0.33, p=8.93x10 -10). The optimal cutoff point was 4.49, with a sensitivity of 82.6% and specificity of 82.1% (AUC=0.889, 95% CI: 0.854-0.924). There were no significant differences in the predictive capacity of the index when evaluated according to gender and age groups. Those individuals with TGI≥4.5 had higher HOMA2-IR averages than those with TGI <4.5 (2.48 vs 1.74, respectively, p<0.001). Conclusions: The TGI is a measure of interest to identify IR in the general population. We propose a single cutoff point of 4.5 to classify individuals with IR. Future studies should evaluate the predictive capacity of this index to determine atypical metabolic phenotypes, type 2 diabetes mellitus and even cardiovascular risk in our population.

Biochemical and clinical characterization of metabolic phenotypes: a cross-sectional study from Maracaibo city, Venezuela

In 1980, Reuben Andresen observed that in certain Background: individuals, obesity did not increase mortality, introducing an atypical phenotype called “healthy obese”. Other studies reported that 10-15 % of lean individuals presented insulin resistance, hyperglycemia and dyslipidemia. The objective of this study was to evaluate biochemical and clinical characteristics of metabolic phenotypes in Maracaibo city. A descriptive, cross-sectional sub-analysis of The Maracaibo Methods: City Metabolic Syndrome Prevalence Study, with a randomized multistage sampling was performed including 1226 non diabetic individuals from both sexes. For phenotype definition, the subjects were first classified according to their BMI into Normal-Weight, Overweight and Obese; then divided in metabolically healthy and unhealthy using a two-step analysis cluster being predictive variables: HOMA2-IR, HOMA2-βcell, triglycerides. To evaluate the relationship with coronary risk, a multiple logistic regression model was performed. In the studied population, 43.9% (n=538) were healthy normal Results: weight, 5.2% (n=64) unhealthy normal weight, 17.4% (n=217) healthy obese and 33.5% (n=411) unhealthy obese subjects. Atypical phenotypes, Metabolically Unhealthy Normal-Weight (MUNW) was more frequent in males (56.3%), whereas Metabolically Unhealthy Obese (MUO) was more frequent in females (51.3%). This phenotypes had a higher coronary event risk, especially for obese individuals (MHO: OR=1.85 CI95%: 1.11-3.09; p=0.02 and MUO: OR=2.09 CI95%: 1.34-3.28; p<0.01). Individuals with atypical metabolic phenotypes are common in Conclusion: Maracaibo city. Related factors may include insulin resistance, basal glucose, and triglycerides levels. Lastly, obese subjects show a higher 1,2 2,3 2 2 2 2 4 2 1 1 1 1 1 1

Omega-3 polyunsaturated fatty acids and cardiovascular health: a molecular view into structure and function

Given the notorious impact of cardiovascular disease (CVD) as the current leading cause of mortality worldwide, the prevention, identification and management of CV risk factors represents a priority in daily clinical practice. Several studies have shown the beneficial effects of dietary omega-3 polyunsaturated fatty acids (PUFAs) on CV health. Their derivatives, eicosapentaenoic acid and docosahexaenoic acid, intervene in multiple metabolic pathways, including: regulation of the inflammatory response, by reducing the synthesis of pro-inflammatory cytokines; regulation of platelet aggregation, activation and adhesion, by modulating thromboxane A2 and plasminogen activator inhibitor-1 activity; regulation of the coagulation pathways, by reducing the carboxylation of vitamin K-dependent coagulation factors; improvement of endothelial function, given their effects on prostaglandin synthesis and endothelial nitric oxide synthase; reduction of serum lipids, through their effects on the hepatic synthesis of triacylglycerides, beta-oxidation of fatty acids and lipoprotein catabolism; and improvement of myocardial function via their membrane-stabilizing effects, and an increase in fluidity, size and distribution of membrane lipid rafts. Nevertheless, these effects appear to vary according to the type of PUFA ingested, dietary sources, daily dosing and individual factors inherent to the subject. Therefore, further studies are required to determine the ideal supplementation for each kind of patient and their particular CV profiles.